Remember Dr. Sin Hang Lee?

If you don’t remember Lee, maybe you remember a while back, when the antivaccine group SaneVax touted findings that it claimed were devastating to Gardasil. Specifically, they claimed that there was vaccine-derived human papilloma virus DNA in Gardasi. Ring any bells yet? And it turns out that the guy who made this apparently horrific “discovery” was—you guessed it!—Dr. Sin Hang Lee. Back in 2011, Lee, apparently either funded by or working with SaneVax, “discovered” that there was DNA in his Gardasil. As I explained at the time, there was a lot less to this claim that meets the eye. Basically, Lee used a very sensitive nested PCR assay to amplify and detect what he claimed to be vaccine-derived sequences from the human HPV strains used to make the vaccine. Specifically, his nested system, as I explained at the time, can radically ramp up the sensitivity of the PCR assay. Of course, it can also radically increase the chances of amplifying a nonspecific strand of DNA.

Given that, it wasn’t too surprising that there might have been minuscule quantities of the recombinant plasmid used to make the protein antigens that go into the vaccine. At least, it wasn’t too surprising to me or anyone with a modicum of knowledge about how sensitive PCR is and how easy it is to get false positives. Even if Lee did everything right and actually did detect a bit of recombinant DNA from the HPV DNA used to make the vaccine. Does this matter? My answer, of course, was no, as was the answer of anyone who knew anything about vaccines and biologics. One factor to consider is how much DNA was present, which was almost certainly very, very little, given that it took nested PCR to detect it.

In fact, even if Dr. Lee’s analysis was completely correct correct and his new, allegedly more sensitive methodology had actually picked up previously undetected traces of HPV DNA from the plasmids used to make the HPV vaccine, it is, as I described before on multiple occasions, incredibly unlikely that such tiny amounts of DNA could cause problems because, as I explained, it’s incredibly difficult to get naked DNA into cells and making the proteins it normally makes, and, even if Dr. Lee were 100% correct about there being undetected HPV DNA in Gardasil, the quantities involved are many orders of magnitude less than what would be needed to have even a whiff of a wisp of a hope of the DNA getting into cells and making its protein. That’s even assuming it could pass the blood-brain barrier or that the DNA fragments were large enough to contain whole coding regions of genes with a proper promoter in front of them to drive their expression. I mean, it’s not as though whole plasmids are likely to have survived the vaccine manufacturing process, and that’s not counting the fact that Gardasil uses a yeast expression system while the other HPV vaccine Cervarix uses a baculovirus (insect) expression system, neither of which would be likely to drive significant expression in human cells.

So what we had was a fear mongering campaign derived from a nonexistent understanding of molecular biology. This campaign reached utterly ridiculous levels when the not-so-dynamic duo of HPV vaccine quackery, Sin Hang Lee and Christopher Shaw (who seems dedicated to the idea that somehow HPV DNA bound to the aluminum adjuvant in the vaccine is deadly) descended like ghouls on the corpses of two young women whose untimely deaths antivaccinationists have been trying to blame on Gardasil ever since they happened. This campaign reached a ridiculous extreme when they actually testified in an inquest in New Zealand into one of these two deaths, a young woman named Jasmine Renata, and tried, in essence, to claim that the poor woman’s body was riddled with HPV and that that HPV caused her death. It was an utterly despicable performance that Shaw, at least, followed up with an article in which he attempted to demonstrate that, in effect, Gardasil killed a young woman. It was not the least bit convincing.

And now Dr. Lee has taken his crack by publishing his paper related to the death of this same young woman in a paper published in an open-access journal I’ve never heard of entitled Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil® vaccination—A case report. Like Shaw’s paper, it’s a massive load of fetid dingo’s kidneys, and it won’t take that long to explain why.

First off, as I’ve always said before, you can tell what you’re in for in a paper by its introduction, and Lee’s introduction is a doozy. It’s full of anti-HPV tropes that would be more at home on the antivaccine propaganda blog Age of Autism (or SaneVax, for that matter). He does, however, inadvertently reveal what I’ve always suspected to be true about this case:

The parents of a formerly healthy New Zealand young woman who suffered a sudden unexpected death in sleep 6 months after Gardasil® vaccination requested testing for the presence of HPV L1 gene DNA in the post-mortem samples of their deceased daughter collected at the time of autopsy. Some of the consultants to the parents suggested that if residual HPV L1 gene DNA which is known to be present in the Gardasil® vaccine [8,9] were present in the postmortem samples, there might be a potential link between the residual HPV DNA and the un- explained death of their daughter. This paper reports the experience in developing a method for the detection and validation of minute quantities of HPV-16 L1 gene DNA in the postmortem blood and spleen obtained at autopsy. The data reported in this paper were extracted from a full report which was submitted to the Wellington coronial court at a public inquest held on August 8-9, 2012.

Who were these “consultants”? One wonders. Were they perhaps Sin Hang Lee and Christopher Shaw, aided and abetted by SaneVax? One wonders, one does. In any case, I wrote about the ridiculousness of letting Shaw and Lee testify at this inquest. One hopes that the committee listened politely and then completely ignored the pseudoscience as embodied in this paper.

So let’s take a look at what Lee did (or claims to have done). He took DNA isolated from these tissue samples and subjected him to his own new super-duper, super special, super sensitive nested PCR, looking for a 190 base pair sequence from the HPV L1 gene. As you might expect, given Lee’s background, there were…problems with his methodology. Rather than critiquing the exact primers he chose and how he went about doing his PCR, let’s step back and look at the experimental design from a bird’s eye view. Basically, he tested DNA from tissue samples from one young woman. There are no controls. How many people in the general population would test positive using Sin Hang Lee’s methodology? We don’t know because he hasn’t made an attempt to find negative controls, and without negative controls we don’t know that every tissue sample would test positive when subjected to his methodology. In fact, the only negative controls I saw mentioned anywhere were negative water controls. That’s perfectly fine to rule out nonspecific amplification that doesn’t depend on DNA (such as artifacts like primer-dimer, but it doesn’t tell you anything other than that.

Another issue is that troubles me is the way that Lee uses degenerate oligonucleotides. It’s worth going back to images I’ve sued before to illustrate nested PCR:

i-2b771ce908cdcfd17c0a348b0076e511-PCR.jpg

And here’s nested PCR:

i-c6eac1e243691b93238b7995321ea691-nested-pcr.gif

Nested PCR can be very, very sensitive, even more sensitive than “simple” PCR, depending upon the number of amplification cycles used in each PCR step. It’s that sensitivity that allows nested PCR to amplify very tiny amounts of target sequence. Now, Lee used a combination of degenerate primers and non-degenerate primers. A degenerate primer is a primer in which some of the positions in the sequence contain more than one base; i.e., there is a mixture of primers with different nucleotides at that place. The reason this is done, generally, is to amplify sequences for which we know there are variations in the sequence. Alternatively, it is done when trying to amplify sequences based on the protein sequence. Because of the degeneracy of the genetic code, most proteins can be coded for by more than one codon of three nucleotides. Usually, the variable base is the third base in the codon, but not always. To account for those nucleotides, degenerate primers are sometimes used as a way of putting a “wildcard” in the positions that can have more than one base in nature. However, such primers have a downside. The more “wild cards” a researcher puts in his primer sequences, the larger the number of potential sites to which those primers can bind. What one gains in sensitivity for potential coding sequences to be detected, one loses in specificity. It’s a tricky balancing act that is not as straightforward as those without much experience in PCR realize.

That’s why in general we avoid using degenerate primers except for this sort of purpose: Trying to isolate a sequence where we know that certain positions can have different bases. If the target sequence that a researcher is trying to amplify by PCR is known (and, make no mistake, the HPV-16 L1 gene sequence used to make HPV vaccine is known), it’s usually a bad idea to use degenerate oligonucleotides, because doing so will decrease specificity and greatly increase the chance of amplifying what I like to call crap. Basically, I can’t figure out why Lee would use the method he’s using. Arguing that there is variability in the natural HPV-16 L1 sequence and he wants to pick that up won’t wash. In fact, he is aiming to detect the vaccine strain sequence; so detecting any natural HPV that might have come from warts or other HPV infections would actually be counterproductive to what he’s trying to accomplish: To detect the vaccine HPV-16 L1 sequence postmortem in Jasmine Renata. It’s almost as though he’s intentionally trying to muddy his findings. Maybe more than almost.

In any case, the same-nested procedure used by Lee, as far as I can tell, involved using degenerate primers for the first round of PCR, and then selecting one set of specific primers that make up the degenerate primer mixture and then using them to repeat the amplification. The idea is to start out less specific and then get more specific by removing the degenerate primers in the second round of PCR. The problem is, of course, garbage in, garbage out. The other problem is, as I said before, we don’t have any negative controls from tissue samples from people who were not vaccinated with Gardasil. The reason this is important is inadvertently described in Lee’s discussion:

Since the human genomic samples contain numerous DNA fragments which are substan- tially complementary to the base sequences of the HPV PCR primers, co-amplification of non-target DNAs of the human genome invariably occurs in the same-nested PCR settings when PCR amplicons are re-amplified with the same primer(s).

Of course, Lee did sequence several of his products. The first sequence was clearly not a pure sequence, but was contaminated with additional sequences, which prevented identification and validation of the PCR product. A couple of the PCR products that Lee sequenced (Figures 6 and 7) were in fact genomic DNA, and it took a lot of fiddling with different primers and conditions for Lee to get fragments that sequenced as HPV 190 base fragments. This suggests to me findings that aren’t robust, which suggests to me that it’s more likely that he’s amplifying contamination than anything else, which, given the multiple rounds of PCR would be very easy to have happen if even a single prep of the plasmid containing HPV L1 were done in the same lab as the PCR of the DNA from tissue samples. That’s yet another reason why controls from tissue samples derived from people who were not vaccinated would be important.

Here’s another thing that would be important. Lee claims that vaccine-derived HPV L1 DNA is somehow hanging around in the body and that it, in essence, might have killed Jasmine Renata. It’s not as if the sequence of the plasmid that is used to make the protein antigen used to make the vaccine isn’t known. Lee only looks at HPV L1 sequence that is inserted in the plasmid. If fragments of the original plasmid used to make the vaccine were in fact still in the vaccine and somehow magically did continue to hang around in the body after vaccination at concentrations detectable by PCR, then it should more than just L1 there. There should be random fragments derived from the whole plasmid, not just the L1 insert. There should be readily identifiable plasmid and promoter sequences. In fact, the sequence I’d look for is a sequence containing overlapping the promoter used in the plasmid. That way, you’d detect HPV L1 sequence attached to the specific yeast promoter used in the manufacturing process connected to known plasmid sequence. It’s the obvious thing to do, because, if that sequence were found, it would be very hard to explain any other way than coming from the plasmid used to make the vaccine. It would even be hard to explain by plasmid contamination because the plasmid containing the HPV-16 virus that Lee bought from ATCC to use as his positive control for PCR reactions because that virus is in Bluescript, which is an E. coli plasmid.

Lee didn’t choose to do that. One wonders why. He even acknowledges that he knows about this issue:

The presence of HPV-16 L1 gene DNA fragments of a vaccine origin indicates possible co-existence of other companion microbial DNA, such as DNA fragments of the plasmid pGAL110 and yeast cells which are used in the vaccine production by the manufacturer [2]. A poten- tial consequence of these viral and microbial DNA frag-ments with their unmethylated CpG motifs in macro-phages [41-46] is to cause release of various cytokines, including tumor necrosis factor (TNF), a recognized myocardial depressant [47-51]. TNF-induced hypoten- sive shock is a documented observation among animals [52,53] and humans [54,55]. To answer the question whether the quantity of these persistent viral or microbial DNA fragments can stimulate the macrophages to release enough TNF to generate a significant pathophysiological impact following Gardasil® vaccination needs expanded research.

Uh, no. Lee should have done the research right in the first place if he wanted to convince anyone by actually looking for the sequences I described above, specifically an amplicon (the DNA target sequence to be amplified by PCR) that encompasses part of the L1 gene, the promoter region used, and pGAL110 sequence that is directly attached to the insert. He could also look for yeast genomic DNA sequences, as he himself suggested. The combination of finding HPV-16 L1 sequences from the plasmid used to make the HPV vaccine plus yeast genomic DNA would be very supportive of his hypothesis. Instead, Lee claims to have amplified L1 DNA fragments “of vaccine origin.” Yet he hasn’t proven that they are of vaccine origin. To do that, he would actually have to amplify some pGAL110 plasmid sequence as well as L1. Then at the end he concocts a handwaving explanation to justify why he had so much trouble amplifying L1 from Jasmine Renata’s tissues when he can amplify HPV L1 DNA from the blood of women infected with HPV-16 in other studies, in which the HPV DNA isn’t in the normal B conformation or is somehow stabilized by binding to aluminum adjuvants. It’s utter nonsense.

Much like everything I’ve seen published by Lee on this topic. No wonder SaneVax and Age of Autism love it so. It’s kind of sad, given that Lee clearly has some skill at PCR, that he chooses to use it for such a silly application in the service of antivaccine fear monger. As a physician with these mad PCR skillz, he really should know better. He should even know just how tiny the amount of HPV-16 L1 DNA there could possibly be in the vaccine, given that he could only detect it with a very sensitive nested PCR test and that that amount is so tiny that it is incredibly unlikely to hang around in the body for more than six months and be detectable in the tissues postmortem, much less cause harm.

Yet Lee chooses not to know.

Comments

  1. #1 Mephistopheles O'Brien
    March 1, 2013

    If cost effectiveness is all we’re concerned about, why aren’t we practicing horse track medicine?

  2. #2 Grant
    March 2, 2013

    Regards “Or that the “Milford Molecular Laboratory” does not in fact seem to exist.” and the like.

    Perhaps there is a company register that can supply details?

    I suspect the best that can be said is that this laboratory has no web presence, at least outside of this SaneVax order form. (PDF file).

    Perhaps the only work MML gets is via these SaneVax orders so Lee/MML and/or SaneVax feels there is no need for a web presence as such?

    A list of Lee’s papers shows the addresses on them have changed from “Department of Pathology, Milford Hospital” for his 2008-2010 papers (in one case giving 300 Seaside Avenue as the street address, which is the hospital address) to “Milford Hospital and Milford Molecular Laboratory, 2044 Bridgeport Avenue” for his 2012 papers, which is across the road from the hospital.

    Searching for “2044 Bridgeport Avenue, CT” brings up Quest Diagnostics and a number of medics and medical services occupying that address. StreetView shows this as grey brick building which I guess has number of suites occupied by various independent workers in addition to Quest Diagnostics.

    Lee might have listed both Milford Hospital and his new location as addresses if he felt the work was done in both places.

    If Lee’s was done without the hospital’s approval, or in a way that the hospital did not approve, then perhaps the hospital would be less than happy with their name being on the papers. You’d have to ask them, really.

    (Certainly I’d like to Lee to have said to the coroner’s inquiry that the work was commissioned by SaneVax: you’d wish autopsy work to be done via players with no vested interests, but SaneVax has a vested interest.)

  3. #3 Grant
    March 2, 2013

    My previous comment (#602) should have been addressed to Narad.

    “If Lee’s was” should read “If Lee’s work was”.

  4. #4 Krebiozen
    March 2, 2013

    Narad,
    On the possibility of eradicating HPV:

    That’s a lofty goal. You have a reservoir and latency to contend with. Quarantine is certainly out.

    A lofty goal perhaps, but I don’t think it’s an impossible one. There’s no non-human reservoir as far as I am aware; the current human one will die off given enough time and people tend to have sex with those of a similar age, making vertical (in terms of age) transmission less common. It would require maintaining high rates of vaccination uptake for a long time, better means of detection and probably effective treatments in addition to vaccination.

    I realize I am being (possibly unrealistically) optimistic about the future of medicine. I don’t think antivaxxers realize the possibilities that vaccines offer, such as eradication of viruses that would ultimately eliminate the need for vaccines against them, so I like to throw the idea into the mix from time to time.

  5. #5 Narad
    March 2, 2013

    Perhaps there is a company register that can supply details?

    Indeed. Plug in business ID 0270302. The listed mailing address on the detail record, 300 Seaside Avenue, is that for the hospital, although the summary record has 2068 Bridgeport. This latter address finally gets one here.

  6. #6 Antaeus Feldspar
    March 2, 2013
    @Anteaus “It would be like making points against a report…”

    I didn’t think you could answer the hard questions or even make a logical comment about the case report. In the words of the infamous Narad, “it must suck being a chickensh.t”

    No, “hard questions” is what your questions would be if the burden of proof wasn’t still on Lee and his supporters to show the soundness of their work. Do you understand this?

    Show us you understand this. “How can you deny the evidence obtained through oneiromancy that says this young woman was killed by a vaccine?” – in a world, such as ours, where oneiromancy has not been shown to produce reliable evidence, do you assert that a question such as this, founded on “evidence” produced through such unsupported methods, is still a “hard question”?

    Since you’re awfully fond of changing the subject and asking new questions, rather than answering the questions asked of you, we’re going to make this an ultimatum question. If you make three comments, on this or any other RI post, without answering the question, it will be taken as an admission that questions relying on unproven methodologies aren’t “hard questions” at all (no matter how convinced devotees of those methodologies are that they are sound and will someday be proven so.)

  7. #7 Narad
    March 2, 2013

    Lee might have listed both Milford Hospital and his new location as addresses if he felt the work was done in both places.

    It is of course normal to list the primary affiliation as that where the work was done, but it’s also normal to indicate (e.g., in a footnote) what the current affiliation is, even if it’s just a home address. This whole presentation just smells fishy, and it goes without saying that SCIRP doesn’t have a staff that minds such details.

  8. #8 Mr Pink
    March 2, 2013

    @narad “One might also note that Lee’s contact E-mail points to an AT&T LEC that doesn’t actually answer on port 25.”

    Many ISP’s have been blocking that port for years. The depths of igorance exposed by that inane observation is telling. Stick to your day job.

    @mephistopheles O’Brien “If cost effectiveness is all we’re concerned about, why aren’t we practicing horse track medicine?”

    We were talking about real life and public health. Since there isn’t enough money to go around, you fund the initiatives that give you the best return on money spent, which of course maximizes the reduction of pain, suffering and death. If you are aware of a better criteria, let’s hear it.

    @lw “Mr Pink misses the difference between mortality and morbidity. As a thought experiment, suppose a hundred women in Rhode Island develop a certain form of cancer, all endure expensive and life-altering treatment (such as surgery, chemo, or radiation), and half of them survive.”

    Thought Experiment Fail: Access to health care reduces cervical cancer mortality not primarily due to the treatment of the disease, but because of access to screening (regular pap tests) helps avoid most of those expensive life altering treatments. And BTW, the cost analysis in the study I referenced uses QALY which factors in all those things you discussed. Vaccine bullies make the same mistake all the time, drawing false conclusions after making grossly invalid assumptions usually based on ignorance.

    @Antaeus “Show us you understand this. “How can you deny the evidence obtained through oneiromancy that says this young woman was killed by a vaccine?””

    Antaeus, you’re really off on some tagent comparing devining through dreams with nested PCR in a lab. I’m worried about you, get some help, please.

    @Grant
    You’re back! You were secretly lurking here all along! Like a worm on a rainy day, the minute Narad starts a new track away from the science, you crawl right out the ground to try to swim in the puddle. All those non-science arguments must really interest you. BTW, the judge down under had no illusions who brought in the “foreign scientists” — the ME sure looked to be a bit lacking in the science department — because he complimented the family in going to get other opinions. Did you even know that?

  9. #9 Mr Pink
    March 2, 2013

    @flip

    Mr Pink doesn’t live in Australia

    Wow, you are perceptive. You’re also right that the US vaccine delivery problems won’t necessarily apply to other countries. Do you want a high five for that perceptive observation too? The only thing Australian public health has to do is keep the faith and hope really hard that the vaccine actually works based on the laughable assumption of 100% efficacy.

    And now we’re off to the races… a nirvana fallacy to begin with.

    It wasn’t me who proposed herd immunity or eradication of HPV. That’s the nirvana fallacy.

    Strawman #2:

    “Here we quite clearly see that Mr Pink is not interested in confirming any analysis that agrees with his point of view, because one paper is enough;”

    I said “I think it is quite useful in pointing out an avenue for investigating some of the more serious reports of reactions.” That doesn’t even come close to meaning one paper is enough. Do they teach different english down under?

    Strawman #3:

    “But he knows it’s silly, so he equivocates with “No I’d not agree with you” but yes “replication is one of the steps”.”

    You said “So you’d agree with me that Lee’s paper is pretty useless until it’s replicated then?”
    There is one key assertion in that statement –> Dr Lee’s paper is pretty useless.
    My response “I think it is quite useful in pointing out an avenue for investigating some of the more serious reports of reactions.” That’s a clear disagreement –> I stated the report was quite useful.
    That’s not equivocating and it’s not ambiguous at all. Pointing out that replication is a natural next step does not weaken or change my position that you were completely wrong in your assertion.
    Claiming that’s equivocating is some dumb.

    “F*k but you walked into that one. Didn’t you bother to pay attention to my questions? Or was I too subtle for you to see the punch line coming?”

    High fives to flip for beating the tar out of that strawman argument! There is a big crater in the ground and the straw stuffing flew 10 feet high in all directions. Hoo-rah.

    Now that you’ve been supremely victorious and killed a whole series of strawmen (or were they strawwomen), do you want to get back to real life and bring a single substantial critique about the case report to the table?

  10. #10 Mr Pink
    March 2, 2013

    @Krebiozen

    “It is you who are suggesting that such RCTs should have been done before vaccine approval.”

    I suggested no such thing. Do you want to beat the tar out of the strawwomen too, because you’re just wasting time making up my arguments and then beating them down in a cloud of straw and dust. You and flip should take reading comprehension classes together.

    “With cervical cancer incidence at around 7 cases per 100,000 women per year in the US you would have to study a very large number of women for at least a year if you wanted to use invasive cancer as an endpoint and have enough statistical power.”

    Whine, whine, whine. HRT studies had 1 million women in the UK and the US based WHI study had 160,000 women. That should be more than enough to get good results on cervical cancer vaccination. Remember, the evidence part from evidence based medicine?

    “Prevention and early detection are two separate things. Using both should enable us to greatly reduce morbidity and mortality, and once incidence of cervical cancer is reduced enough no doubt screening protocols will be changed.”

    Screening is required because the vaccine only targets specific strains and other strains can cause cervical cancer. Screening already drastically reduces both the mortality and morbidity from cervical cancer. You saw the quote from Ian Frazer: the vaccine’s most obvious use is the developing world, not where people have good access to healthcare.

    If you really think that a condition that causes suffering and death in thousands of people every year is too rare for it to be worthwhile adopting measures to prevent it, then I can only disagree with you.

    Really, the pain and suffering gambit, from the same guy who stormed out here lecturing about public health needing to take gambles? What would happen if you applied that money to reduce medical error which causes way more suffering and death than cervical cancer and is one of the leading causes of death in the US? Which approach reduces more suffering and death? What causes more pain and suffering for others: an unnecessary death due to a mistake by the medical community, or death by disease?

    If you accept surrogate markers as viable, and you have presented no good reasons not to, then there is no circular reasoning.

    Aye, but that’s the point isn’t it? This core argument is about the validity of the choice of surrogate outcome. I’ve produced good evidence to support that CIN-2 is not a very accurate surrogate at all and certainly is not universally accepted as such. You’re the one bringing up the ethical argument to counter it. You can’t counter a lack of efficacy argument with ethics because that creates the circular reasoning.

    If we knew in advance which cases of HPV will progress to cervical cancer, we wouldn’t need to vaccinate against it or even treat it, except in those cases, would we?

    I am saying exactly that, we don’t need to vaccinate against it where you have good access to healthcare. There are many well known risk factors associated with cervical cancer. The real problem is none of them involve pharmaceutical profit. That’s the case with the most expensive chronic diseases as well in case you hadn’t figured that out yet.

    Use whatever figures you prefer, though gun deaths and medical errors are an irrelevant tu quoque here… Also, you may not be concerned about the health of those in the developing world, but I am.

    You are the one who brought public health into the argument at the beginning. High causes of death always involve public health (including guns, google it) so those stats are entirely relevant because the money you’re wasting on the vaccine could save a lot more people if spent elsewhere. There was no fallacy there.

    “Gardasil is recommended for 11- and 12 year-old girls, and also females 13 through 26-year-old who were not previously vaccinated”, remember? If this recommendation is followed then most girls will be vaccinated before they are exposed.

    In the poor states, you aren’t anywhere near 100% coverage. In the age range of 13-26 what percentage of girls and women have not been exposed to HPV?

    The statement that “Vaccination against HPV-16 and HPV-18 is expected to be economically attractive (i.e., <$50,000 per QALY) if high coverage can be achieved in the primary target group of 12-year-old girls and if vaccine-induced immunity is lifelong." supports my arguments, does it not? If there was less misinformation about vaccine safety being disseminated perhaps it would be easier to achieve greater vaccine coverage and it would be even more economically viable.

    You didn’t read my reference from Bach did you? He uses the Kim et al study and points out that unless you vaccinate the populations at high risk in the US (i.e. the poor states without access to health care) the initiative is no longer cost effective (I pointed out Narad’s foot-in-mouth by showing the large differences in cervical cancer mortality rates between wealthy and poor states). Unfortunately, you are not vaccinating the poor states properly, so the initiative is no longer cost effective. And since you clearly have problems with comphrehending this point I will spell it out for you: low rates of vaccination in poor populations in the US is due to lack of access to health care, NOT safety concerns so your false argument about misinformation is rhetorical musing, nothing more.

    I didn’t say that “half the efficacy is still cost effective”, I talked about “worth” in which I would include non-economic factors. Economic attractiveness is a subjective measure, and QALYs are a controversial way of quantifying human well-being.

    Slow down there fast one. QALY is the way public health quantifies the “worth” of a medical intervention. You invoked both public health and efficacy proving worth. You referenced the study that does the calculation using QALY!. You’re trying to move the goalpost AGAIN, and now I suppose you would choose to retract that reference now right?

    Are you really incapable of clicking on the links in the list of ‘Related Scientific Articles’ at the bottom of the CDC webpage that I linked to?

    I missed the Gee study on VSD, the other one you linked was VAERS which I already addressed. Did you read the study? (I sense a pattern here) They only looked for pre-determined outcomes (pre-specified ICD-9 codes) which is very different from a thorough safety analysis. This is what the CDC says on their site: “This is because pre-licensure trials are often too small to detect rare events and special populations may not be adequately represented.” So how does studying pre-determined outcomes help “detect rare adverse events that were not identified during pre-licensure clinical trials?”
    One single study which was limited to pre-determined adverse events + one study on VAERS which gets a small fraction of unreliable reports “plenty of post-marketing evidence to suggest HPV vaccines are remarkably safe…”
    Cognitive dissonance?

    BTW, Did you ever figure out why that systematic review you posted doesn’t count as post-marketing evidence?

  11. #11 Mr Pink
    March 2, 2013

    @Krebiozen

    Why is it a pipe dream to suggest that in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated?

    OMG, you have really exposed your ignorance on vaccination with that one. Do you have any idea how smallpox was actually eradicated? Are you even aware that herd immunity for pertussis (one of the older vaccine preventable diseases) is a pipe dream? It is true irony that the same poster who erroneously quipped that I invoked the nirvana fallacy, turns around and suggests that HPV could be eradicated through vaccination. It is such a ridiculous suggestion that Narad (the self appointed referee) had to politely come by and tell you to back away from that one because you’re making his side look really bad.

    “I don’t have an economic model, I am suggesting that HPV infection leads to economic costs and also causes unquantifiable human suffering that I believe is worth tackling through vaccination.”

    I see you’ve really shifted the goalpost now. Let’s take a trip back to Post #547:
    “Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality.” –> Apparently now, you’re claiming that this was a statement of opinion not based on any evidence at all.

    Your arguments are all over the place. You invoked public health by storming into this argument with definitive statements of confidence in the vaccine program lecturing about taking gambles in public health: “Public health decisions like this are always a gamble to some extent. … We never have the luxury of certainty in the arena of public health.” When you invoke public health the term “worth” is well defined. I suppose by your new argument (i.e. shifted goalpost), public health should be gambling — in an era with of scarce funding — without evidence, or even an economic model.

    Ignoring your over the top comments about safety, you assert that the vaccine is successful before a single shred of evidence has even been collected regarding the desired endpoint of cervical cancer.
    “We have every reason to believe the vaccine will reduce the incidence of cervical cancer.”
    “The evidence also shows beyond any reasonable doubt that the presence of precancerous cervical lesions is predictive of cervical cancer.”

    You use inaccurate and completely definitive terms to characterize the state of evidence.
    It has been proven to reduce the risk of cervical changes that are known to be associated with cervical cancer in the short term

    When shown that your surrogate outcomes are far from a sure thing, you back off the unscientific language and you invoke:
    False argument of authority –> The WHO and FDA says so, therefore it must be the right decision.
    False argument of popularity –> Everyone else is doing it
    Circular reasoning –> It must be effective because it’s unethical to study the endpoint

    None of these arguments are evidence based and they don’t support your notion that CIN-2 is a credible surrogate for cervical cancer. The first preliminary real life evidence of HPV prevalence in the population blows the confident predictions right out of the water.

    Now you’re furiously backpedalling and invoking emotional arguments like “pain and suffering” and caring for the developing world. I’ll take that as a concession because the program we’ve been discussing here isn’t focused on the developing world and public health decisions shouldn’t be based on emotional arguments. “Pain and suffering” will be reduced if public health spends it’s money in the most effective way, but that requires cost models and quantitative measures.

    I applaud your intentions on reducing morbidity and mortality, and I sincerely believe you have the right motives. The problem IMO, is that your faith (“We have every reason to believe the vaccine will reduce the incidence of cervical cancer.”) is misplaced in a program that is based on seriously flawed assumptions for the developed world. Because of that, it has a high probability of being an enormous waste of money. Money that would be far better spent elsewhere reducing morbidity and mortality in your developed country.

  12. #12 Narad
    March 2, 2013

    Many ISP’s have been blocking that port for years. The depths of igorance exposed by that inane observation is telling. Stick to your day job.

    Perhaps you don’t grasp the point. Perhaps you would like to try dropping him a line using a normal sendmail client.

  13. #13 Narad
    March 2, 2013

    (For those unfamiliar with Pink’s claim of “depths of ignorance,” many ISPs block outbound port 25 to prevent their clueless customers from functioning as botnet nodes.)

  14. #14 Narad
    March 2, 2013

    It is such a ridiculous suggestion that Narad (the self appointed referee) had to politely come by and tell you to back away from that one because you’re making his side look really bad.

    I didn’t tell K. to “back away from” anything, I said that eradication is a lofty goal, the practicalities of which he readily acknowledged.

  15. #15 Mr Pink
    March 2, 2013

    CORRECTION in Post 610:
    The parser ate my do not equal sign. It should read:

    @krebiozen:
    One single study which was limited to pre-determined adverse events
    + one study on VAERS which gets a small fraction of unreliable reports
    DOES NOT EQUAL
    “plenty of post-marketing evidence to suggest HPV vaccines are remarkably safe…”

  16. #16 Mr Pink
    March 2, 2013

    @Narad “Perhaps you don’t grasp the point. Perhaps you would like to try dropping him a line using a normal sendmail client.”

    Now that really is some dumb. Serious mail providers typically only accept traffic on port 25 from pre-approved MTAs, not personal mail servers. You should be originating your mail connecting through an MSA on port 587, unless you’re trying to hide something or spam email that is.

  17. #17 Mr Pink
    March 2, 2013

    @Narad “I didn’t tell K. to “back away from” anything, I said that eradication is a lofty goal, the practicalities of which he readily acknowledged.

    Lofty goal? I said it was a polite warning. He didn’t acknowledge the key missing ingredient of quarantine at all — which indicates he doesn’t understand how smallpox was really eradicated.

  18. #18 Grant
    March 2, 2013

    Narad,

    re, #605: MML is “a subsidiary of Milford Hospital”, then – so Lee has the work as being done entirely within Milford Hospital. OK, good that’s sorted. Not what I was expecting though given, I thought, Milford had disemployed him at an earlier date, but it makes the outcome of the legals more interesting I suppose (?)

    re, #607: “but it’s also normal to indicate (e.g., in a footnote) what the current affiliation is” – Originally wrote as much in my comment, but canned it.

  19. #19 LW
    March 2, 2013

    A key difference between smallpox and HPV is that smallpox spreads through the air and HPV does not. Hence, one person with smallpox could infect an entire jumbo jet full of passengers during one trans-Atlantic flight, whereas it would be relatively uncommon for a person to infect an equivalent number of other people with HPV even over the course of a lifetime. Hence, the need for quarantine with smallpox does not necessarily imply an equivalent need for quarantine with HPV.

  20. #20 Narad
    March 2, 2013

    Now that really is some dumb. Serious mail providers typically only accept traffic on port 25 from pre-approved MTAs, not personal mail servers. You should be originating your mail connecting through an MSA on port 587

    This betrays extreme stupidity. Do you even actually know what an MTA is? Don’t try to teach your grandmother how to suck eggs.

  21. #21 Narad
    March 2, 2013

    Hence, the need for quarantine with smallpox does not necessarily imply an equivalent need for quarantine with HPV.

    True enough, but commensurately, tactics such as ring vaccination are out. This will be a long-term endeavor, as K. has noted. You just don’t know where it “is.”

  22. #22 Narad
    March 2, 2013

    Lofty goal? I said it was a polite warning.

    You said no such thing. Your words were that I “had to politely come by and tell [Krebiozen] to back away from that one because you’re making his side look really bad.”

    I issued no “warning,” and I did not tell K. to “back away from” anything.

  23. #23 Narad
    March 2, 2013

    Serious mail providers typically only accept traffic….

    /Users/narad> telnet gmail.com 25
    Trying 74.125.142.83…
    ^C
    /Users/narad> telnet gmail.com 80
    Trying 74.125.142.83…
    Connected to gmail.com.
    Escape character is ‘^]’.
    ^C
    /Users/narad> telnet gmail.com 587
    Trying 74.125.142.83…
    ^C

    Get it yet?

  24. #24 Narad
    March 2, 2013

    Allow me to clarify further.

    /Users/narad> telnet smtp.gmail.com 25
    Trying 74.125.133.108…
    Connected to gmail-smtp-msa.l.google.com.
    Escape character is ‘^]’.
    220 mx.google.com ESMTP dy5sm4338538igc.1 – gsmtp
    ^]
    telnet> close
    Connection closed.

  25. #25 LW
    March 2, 2013

    “True enough, but commensurately, tactics such as ring vaccination are out.”

    Oh, granted. Mr Pink was sneering at Krebiozen for not mentioning quarantine in connection with potential eradication of HPV. I was pointing out that quarantine isn’t as relevant to HPV as it was to smallpox so there wasn’t really any reason for Krebiozen to bring it up.

    Also, Mr Pink doesn’t grasp the meaning of “thought experiment.”

  26. #26 Narad
    March 2, 2013

    To close the position,

    /Users/narad> dig -t mx snet.net

    ; <> DiG 9.3.6-APPLE-P2 <> -t mx snet.net
    ;; global options: printcmd
    ;; Got answer:
    ;; ->>HEADER< telnet nb-mx-vip1.prodigy.net 25
    Trying 207.115.36.20…
    Connected to nb-mx-vip1.prodigy.net.
    Escape character is ‘^]’.
    220 nlpi167.prodigy.net ESMTP Sendmail 8.14.4 IN/8.14.4; Sat, 2 Mar 2013 16:28:34 -0600
    ^]
    telnet> close
    Connection closed.

    See? I was wrong, but in kneejerk response, you were even wronger.

  27. #27 Narad
    March 2, 2013

    Hmph, that got oddly truncated midway. Anyway, the ‘dig’ yields the prodigy.net MXs that happily answer on port 25; it’s easy enough to test for oneself.

  28. #28 Krebiozen
    March 2, 2013

    I will reply to Mr. Pink anon, though I get the feeling we are going in ever diminishing circles. Meanwhile, I am not the only person to suggest it might be possible to eventually eliminate HPV and cervical cancer.

    There’s an interesting webcast on the subject here as well if anyone’s interested.

  29. #29 Krebiozen
    March 2, 2013

    Humph. WordPress chewed up that URL. Try this page, ‘Cervical cancer and vaccination- an overview’.

  30. #30 Shay
    March 2, 2013

    . I will spell out the point since it apparently wasn’t obvious enough: It’s a waste of money to vaccinate the people with good access to health care but that’s exactly what you’re doing in the US. You are not actually vaccinating the people who the vaccine was designed to help.

    I don’t know where to start…Adam, I feel your pain.

    It’s a waste of money to vaccinate people with access to health care? Holy steamin’ pile o’ stupid. Yes, my friends, let yourselves and your kids risk genital warts, RRP, and vulvar, vaginal, anal or oropharyngeal cancer because treating these is so much cheaper than a shot.

    We’re not actually vaccinating the people that the vaccine was designed to help? Per the CDC, HPV is now so common that all sexually active adults are at risk, not just the po’ folks.

    FYI, the vaccine is now offered by many health departments as part of the vaccination program for children from low-income families.

  31. #31 Krebiozen
    March 2, 2013

    There are some interesting snippets in that webcast. For example a 50% reduction in genital warts has already been seen in younger (vaccinated) women in Melbourne, but not in older (unvaccinated) women, so it must be due to the vaccine. A similar reduction has been seen in genital warts in young heterosexual men (unvaccinated), presumably due to the herd immunity that Mr. Pink claims is a pipe dream. Also, you need to vaccinate 31 girls to prevent a case of CIN-2/3, 639 girls to save 1 life, and 14 girls to save 1 year of life, figures that are much lower than for other vaccines, which rather elegantly expresses what I have been trying to explain, perhaps somewhat inarticulately, about the value of the vaccine. Finally, polyvalent vaccines were in Phase 3 clinical trials in 2009 so presumably will be within a few years.

  32. #32 Krebiozen
    March 2, 2013

    “presumably will be available within a few years”

  33. #33 Antaeus Feldspar
    March 2, 2013

    Let it be noted that Mr. Pink definitely saw the ultimatum question, even quoted from it, but posted three comments without even attempting to answer. As warned, Pink’s attempts to avoid the question will be taken as an admission that Lee’s supposed “evidence” against Gardasil is utterly meaningless until and unless Lee’s methodologies become accepted, verified science.

    Of course, Pink will claim that Lee’s methodologies already are accepted, verified science. This is false.

    This paper reports the experience in developing a method for the detection and validation of minute quantities of HPV-16 L1 gene DNA in the postmortem blood and spleen obtained at autopsy.

    That’s from Lee’s own paper; Lee himself is admitting that his methodology is novel. Any fool who claims that Lee’s results must be as solid as those obtained through standard techniques of nested PCR because Lee’s newly developed method also employs nested PCR, doesn’t understand Lee’s own paper and has no credibility when assuring us how very convincing it is.

  34. #34 Krebiozen
    March 3, 2013

    LW,

    I was pointing out that quarantine isn’t as relevant to HPV as it was to smallpox so there wasn’t really any reason for Krebiozen to bring it up.

    I would suggest that it is HPV antibody testing and the use of safe sex or abstention in those who test positive that will be analogous to the use quarantine in the eradication of smallpox. It wasn’t that long ago I was trying in vain to explain to Th1Th2 that it was the use of surveillance, isolation and vaccination together that eliminated smallpox, with her insisting that the vaccination part was unnecessary.

  35. #35 LW
    March 3, 2013

    I think you need to get the prevalence down via vaccination before antibody testing is practical. If something like half the adult population is exposed, you can’t very well test everyone and urge safe sex or abstention just on the exposed. Anyway, everyone should be encouraged to act in ways that reduce the spread of HPV, as well as other such diseases.

  36. #36 Krebiozen
    March 3, 2013

    LW,

    I think you need to get the prevalence down via vaccination before antibody testing is practical. If something like half the adult population is exposed, you can’t very well test everyone and urge safe sex or abstention just on the exposed.

    I agree. Eradication in this way this would require a long-term strategy over the next 50 years or more.

    Anyway, everyone should be encouraged to act in ways that reduce the spread of HPV, as well as other such diseases.

    True, but that’s not entirely practical if you want to reproduce.

    BTW I would add an effective treatment for HPV infection to my expectations (or perhaps utopian wish-list) for future medical developments.

  37. #37 Mr Pink
    March 3, 2013

    @Krebiozen “There are some interesting snippets in that webcast. For example a 50% reduction in genital warts has already been seen in younger (vaccinated) women in Melbourne, but not in older (unvaccinated) women, so it must be due to the vaccine.”

    If you read that graph carefully, each datapoint was 3 months, making it look like a much longer study than it was. I followed the reference. That data was from a clinic that treats a specific population. After they vaccinated the population starting in 2007, they saw a decrease in genital warts in 2008 (that’s when the data ends). I would certainly hope to see some vaccine efficacy during in the period of one year! If you didn’t see anything, the vaccine would immediately be declared a dismal failure. These results are hardly startling. It’s long term efficacy that matters across a large population. Most of the rest of the slide deck regurgitates the data from the clinical trials which we’ve already covered to death. One thing that jumps out is the amount of ADRs from the Placebo. Do you think that it might just be because their “placebo” isn’t really one?

    @Krebiozen “Also, you need to vaccinate 31 girls to prevent a case of CIN-2/3, 639 girls to save 1 life, and 14 girls to save 1 year of life, figures that are much lower than for other vaccines, which rather elegantly expresses what I have been trying to explain, perhaps somewhat inarticulately, about the value of the vaccine.”

    You didn’t factor in the cost. That’s like saying I want to build and buy the safest car regardless of the cost. CDC Cost: Gardasil costs ~$300, DTaP ~$60, MMR ~40. That’s almost an order of magnitude more expensive than MMR. Public health can’t ignore cost as a criteria for deciding on initiatives.

    @Krebiozen “I would suggest that it is HPV antibody testing and the use of safe sex or abstention in those who test positive that will be analogous to the use quarantine in the eradication of smallpox.”

    I think the odds of success there are close to zero. People still engage in unsafe sex, even when the penalty is/was death from HIV/AIDS. Why would the fear of genital warts have a greater chance of success? People don’t require proof of an AIDS test today, let alone an HPV test. Call me a sceptic, but I just can’t see that flying unless you decided to create a police state where everyone had to carry around ID with test results on it.

    @Shay “It’s a waste of money to vaccinate people with access to health care?…”

    If you disagree with the Bach reference, then post an alternate financial model which supports your rhetorical fury.

    @Shay “FYI, the vaccine is now offered by many health departments as part of the vaccination program for children from low-income families.”

    Do you have stats to show it’s working? The state numbers from the CDC still don’t look so good. The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money. Hopefully they can clean up their early failure.

  38. #38 Narad
    March 3, 2013

    CDC Cost: Gardasil costs ~$300, DTaP ~$60, MMR ~40. That’s almost an order of magnitude more expensive than MMR.

    You’re now reduced to whining about the cost of the vaccine while simultaneously, in effect, advancing the “Pap smears are better” argument? The incremental lifetime cost is effectively nothing. What’s the cost of treating cervical cancer?

  39. #39 herr doktor bimler
    March 4, 2013

    You’re now reduced to whining about the cost of the vaccine while simultaneously, in effect, advancing the “Pap smears are better” argument?

    If I understand correctly, the cost comparison is between (a) a vaccine of some form or (b) the SaneVax / Sin Hang Lee business model of “Pap smears plus regular payments from every woman regularly through her lifetime to SaneVax for a dodgy PCR test “.

  40. #40 Julian Frost
    NOYDB
    March 4, 2013

    @Mr Pink:

    You didn’t factor in the cost. CDC Cost: Gardasil costs ~$300…That’s almost an order of magnitude more expensive than MMR. Public health can’t ignore cost as a criteria for deciding on initiatives.

    Seriously?!?! Have you never heard of the expression “Prevention is better than cure”? It can cost tens of thousands of dollars to treat just one case of cervical cancer. Even if the patient survives, there can still be lasting damage. I read that Brooke Shields’s battle with cervical cancer permanently damaged her uterus and consequentially, her two daughters had to be delivered by C-Section. In addition, HPV has been implicated in cancers in males, and in cancers of the mouth and throat.
    A $300-00 jab is looking like a very good, cost effective option.

  41. #41 herr doktor bimler
    March 4, 2013

    don’t you think it’s a little disingenuous that Lee declares no conflicts of interest despite the fact the he has a clear financial interest in the LoTemp PCR system?

    A thorough conflict-of-interest declaration would also include the direct competition between (a) vaccination campaigns that Lee and SaneVax have worked so hard to undermine, and (b) the program of regular PCR screening offered by Lee and SaneVax at $50 per person per test (possibly reimburseable).
    http://www.businesswire.com/news/home/20100920005586/en/S.A.N.E.-Vax-Sin-Hang-Lee-MD-Offers

  42. #42 Shay
    March 4, 2013

    If you disagree with the Bach reference, then post an alternate financial model which supports your rhetorical fury.

    Which would you rather purchase — a smoke detector or a brand-new house?

    Prevention costs less than treatment. I have insurance and can afford to get treatment for diabetes and high cholesterol but I’d rather keep my weight under control; it’s cheaper in the long run. However, if you can’t be made to see how this makes sense from a medical standpoint, I’m not sure an argument from a business perspective is going to convince you.

    You didn’t factor in the cost. CDC Cost: Gardasil costs ~$300…That’s almost an order of magnitude more expensive than MMR. Public health can’t ignore cost as a criteria for deciding on initiatives.

    Are you seriously arguing that treatment for cervical or oropharyngeal cancer costs less than $300?

  43. #43 Mr Pink
    March 4, 2013

    @Julian Frost “Seriously?!?! Have you never heard of the expression “Prevention is better than cure”? It can cost tens of thousands of dollars to treat just one case of cervical cancer. “

    @Shay “Which would you rather purchase — a smoke detector or a brand-new house?”

    Two almost identical strawmen. Did you people not read the context of the discussion? Krebiozen was comparing various vaccines and the vaccination/prevention ratio compared to other vaccines. Do I really need to point out that cost and ROI is one of the most important criteria when choosing public health initiatives? Arguing that I am against preventative measures is a strawman.

    The Bach reference clearly outlines that in order for the preventative measure to be cost effective (i.e. positive ROI) we need to vaccinate the populations without access to health care because they have a higher risk of cervical cancer.

    Unlike far more targeted preventative measures — like providing screening to high risk groups — you are advocating we pay for an unnecessary procedure for the whole population, the vast majority of whom are not at risk of anything.

    Of course, if you people want to continue living in a fantasyland where you assume infinite funding — apparently you are in good company in America today — go ahead and keep drinking the kool-aid corporate america is feeding you.

    @Krebiozen “I would suggest that it is HPV antibody testing and the use of safe sex or abstention in those who test positive that will be analogous to the use quarantine in the eradication of smallpox.”

    That would not work. From the CDC: “As HPV infection is confined to the epithelium and infected cells are shed before cell death, natural HPV infection results in minimal host immune response and not all those infected have detectable antibodies”

    @Grant “If Lee’s was done without the hospital’s approval, or in a way that the hospital did not approve, then perhaps the hospital would be less than happy with their name being on the papers. You’d have to ask them, really.”

    Any luck getting a public statement from the “affiliated party” yet? All those allegations of fraud sound like a lot of hot air.

  44. #44 Narad
    March 4, 2013

    Unlike far more targeted preventative measures — like providing screening to high risk groups — you are advocating we pay for an unnecessary procedure for the whole population, the vast majority of whom are not at risk of anything.

    I award you no points, and may G-d have mercy on your soul.

  45. #45 Grant
    March 4, 2013

    Mr Pink,

    Regards “@Grant […] Any luck getting a public statement from the “affiliated party” yet? All those allegations of fraud sound like a lot of hot air.”

    I wasn’t the person asking for a public statement. Nor did I make an “allegation of fraud”. You need to read more carefully. (It’s pretty rich how you accuse others of not reading carefully when you certainly aren’t yourself!)

    I would remind you—again—that accusing people writing here of things they haven’t done and the various other silly put-downs you do with regularity won’t make you or Lee right.

  46. #46 Julian Frost
    March 5, 2013

    @Mr Pink:

    Do I really need to point out that cost and ROI is one of the most important criteria when choosing public health initiatives?

    How ironic. You accuse me and Shay of strawmanning and yet you yourself straw man. The ROI on the HPV vaccine is excellent. We accused you of miscalculating the ROI.

    The Bach reference clearly outlines that in order for the preventative measure to be cost effective (i.e. positive ROI) we need to vaccinate the populations without access to health care because they have a higher risk of cervical cancer.

    A higher risk of cervical cancer, or a higher risk of dying from it? Also, treating a case of cervical cancer costs a ton of money, whether or not the patient has access to health care. It’s still cheaper to vaccinate.

  47. #47 Krebiozen
    March 5, 2013

    A quick response to Mr. Pink as I am currently otherwise occupied:

    That would not work. […] not all those infected have detectable antibodies

    Not all, but most do. I am suggesting this as part of a larger strategy to eradicate HPV. As I wrote before, it would require a long time, and quite probably technologies not yet developed. In theory all we have to do is reduce the average number of people each infected individual infects to less than one for long enough; there are several different and complementary ways of doing this. They have to be tailored to HPV and its modes of transmission just as the different complementary methods used to eradicate smallpox were.

  48. #48 Shay
    March 5, 2013

    @Pink

    Nice dodge. I say again, are you seriously arguing that a $300 vaccination is more expensive than treatment for cancer?

  49. #49 JGC
    March 5, 2013

    Since not veryone infected with HPV will develope cancer as a results, I think he’s arguing that $300 dollars per person to vaccinate enough people to prevent a case of crvical cancer costs more than treating that case of cancer.

    I don’t know if that’s true–the cost of treating cancer can easily run into 6 figures–but even if it were that >isn’t an argument against HPV vaccination: it’s instead an argument in favor of reducing the per person cost of HPV vaccination.

  50. #50 herr doktor bimler
    March 5, 2013

    All those allegations of fraud sound like a lot of hot air.

    I don’t know; Sin Hang Lee’s activities as a cancer scammer are not in question.
    I particularly liked the part of the story where he demanded that the FDA should shut down rival (non-medicinal) tea traders.

  51. #51 Narad
    March 5, 2013

    Since not veryone infected with HPV will develope cancer as a results, I think he’s arguing that $300 dollars per person to vaccinate enough people to prevent a case of crvical cancer costs more than treating that case of cancer.

    It’s still a drop in the bucket amortized against the extant cost of screening.

  52. #52 Grant
    March 5, 2013

    herr doktor bimler,

    Just to be clear, my previous objections (#645) were to Mr Pink getting confused about who wrote what again.

  53. #53 Mr Pink
    March 5, 2013

    @Julian Frost “We accused you of miscalculating the ROI.” … “It’s still cheaper to vaccinate.”… “A higher risk of cervical cancer, or a higher risk of dying from it? “

    It wasn’t my calculation, that came from the reference which you didn’t read very carefully. It says: “Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective.” That’s disease, not death.

    @shay “Nice dodge. I say again, are you seriously arguing that a $300 vaccination is more expensive than treatment for cancer?”

    You appear clueless on how to measure the ROI of a public health measure. Read the post from JGC who gets it.

    @jgc “I don’t know if that’s true–the cost of treating cancer can easily run into 6 figures–but even if it were that isn’t an argument against HPV vaccination: it’s instead an argument in favor of reducing the per person cost of HPV vaccination.”

    The model was just below the threshold of economically attractive (< 50K) if only 12 year olds were vaccinated. It's over 6 figures if you catch up to age 26. That's why Bach points out that ineffective delivery makes the program not economically attractive. Also, that number was based on the rosy assumption of lifelong immunity. The cost is well over 6 figures if immunity lasts only 10 years as they project only a marginal reduction of 2% over current screening in that scenario.

    This is just a model based on a whole host of assumptions because there is no efficacy data available yet. I don't think there has been a single early vaccine cost model (i.e. prior to seeing actual efficacy in real life) that didn't grossly underestimate the cost. 1 shot of MMR was supposed to give immunity for life too. Even 2 shots still don't prevent a mumps outbreak today blowing the older cost calculations out of the water.

    Given that Merck just lost patent protection on one of their biggest drugs (Singular @ 5.5B annual revenue in 2011), I doubt they will be dropping the price anytime soon.

  54. #54 Mr Pink
    March 5, 2013

    @Krebiozen “Not all, but most do. I am suggesting this as part of a larger strategy to eradicate HPV. As I wrote before, it would require a long time, and quite probably technologies not yet developed.”

    LOL, most? Did you check the confidence interval on that 51% number? A more accurate term would have been half. The “technologies not yet developed” make this sound an awful lot like wishful or magical thinking. According to our host, that puts it right up there with homeopathy.

  55. #55 Narad
    March 5, 2013

    Tell us what the nudists do on port 587, Pink.

  56. #56 Narad
    March 5, 2013

    Oh, sorry, “LOL.” I’d hate to appear not to have a measure of technological sophistication.

  57. #57 Narad
    March 5, 2013

    It wasn’t my calculation, that came from the reference which you didn’t read very carefully. It says: “Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective.” That’s disease, not death.

    You didn’t read the underlying reference, did you?

  58. #58 Narad
    March 5, 2013

    I suppose I should add, from the original (PDF),

    Overall, Blacks and non-Hispanic whites have
    been noted to have the highest cervical cancer screening rates among all ethnic groups, whereas Hispanics and AA/AN/PI women are less likely to have ever had a Pap or to have been screened within the past 3 years.

    [Footnotes omitted, emphasis added.]

  59. #59 Julian Frost
    NOYDB
    March 6, 2013

    @Mr Pink:

    “Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective.”

    A pap smear detects the disease in the early stages where treatment is cheapest and most likely to be effective. However, it’s still more expensive than the vaccination. The ROI still favours the vaccine.

  60. #60 Krebiozen
    March 6, 2013

    Mr. Pink,
    I’m starting to simply repeat myself, which is a waste of everyone’s time. I think there is ample evidence to support the assumption that Gardasil will prevent cervical and other cancers, and that it will prove to be a safe, effective and cost-effective intervention in the long term. Perhaps we should reconvene here in a decade or two to assess how well it has done.

    Anyway, I note that you appear to have changed your position from:

    There isn’t an ounce of quality evidence showing the vaccine has or will ever reduce the incidence of cervical cancer. That’s why people should avoid Gardasil, not because of one linked death.

    To:

    The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money. Hopefully they can clean up their early failure.

    Which is progress of sorts.

    I will address this cheap shot:

    The “technologies not yet developed” make this sound an awful lot like wishful or magical thinking. According to our host, that puts it right up there with homeopathy.

    I originally wrote, “in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated”. I have stated that I might be being “unrealistically optimistic” and that this might require “technologies not yet developed” . We know that polyvalent HPV vaccines are currently undergoing RCTs, and that antiviral drugs targeting HPV are under development. As I pointed out above, I am not alone in thinking it might be possible to eradicate HPV eventually.

    Wishful thinking? Perhaps.
    Magical thinking? Certainly not .

  61. #61 Krebiozen
    March 6, 2013

    One more thing – I was getting HPV testing confused with HPV antibody testing earlier. Testing for HPV is considerably more sensitive than cytology though less specific. There’s a recent paper on the future of cervical cancer screening here if anyone’s interested. It concludes:

    It is entirely conceivable that women will no longer die from cervical cancer in the near future, thanks to global effective screening and preventive efforts through widespread HPV vaccination.

    I think that’s worth pursuing.

  62. #62 JGC
    March 6, 2013

    Mr. pink, just for teh record I don’t agree that the ROI for the vaccine is insufficient–quite the opposite. One doesn’t have to prevent very many cases of cervical cancer to achieve cost effectiveness.

    As for Bach’s claims that ineffective delivery making the program economicallu unattractive, that’s again not an argument against immunization–it’s an argument in favor of optimizing the delivery program.

    with regard to pap smears versus immunization, fail to see the relevance to this discussion. Regular pap screening is capable only of detecting cervical cancer once it arises, while immunization prevents its occurrence. Would you similarly argue that there’s no need to expend resources preventing the sale of guns to convicted felons, long as we can accurately determine after the fact when a felon has purchased a firearm?

  63. #63 Shay
    March 6, 2013

    You appear clueless on how to measure the ROI of a public health measure. Read the post from JGC who gets it.

    Yes, JCG gets it…you, on the other hand, don’t.

  64. #64 Grant
    March 6, 2013

    Krebiozen, “I’m starting to simply repeat myself, which is a waste of everyone’s time.” – similar for me. I felt sometime ago (what is it now, two weeks ago?) that it got to the point where all I could suggest was for him to re-read earlier comments as he clearly wasn’t taking things in and was just pushing his own barrow.

  65. #65 Mr Pink
    March 6, 2013

    @narad “You didn’t read the underlying reference, did you?”

    You stopped reading after you found the quote you wanted. In the same paragraph: “Other studies have suggested that [b]race/ethnicity is likely not the primary mediator of disparities in cervical cancer screening rates[/b]… This is evidenced by the fact that the effect of race is significantly reduced or eliminated after controlling for these factors.”

    Further down in the study: “In a number of these studies, socio-economic position has been noted to explain differences in cervical cancer screening rates better than race/ethnicity.”

    Of course, the heart of the matter is put to rest further down: “Lack of access to health care has been correlated with reduced cervical cancer screening and treatment. In most studies, health care access is measured by insurance status or having a usual source of care. Having insurance, particularly private insurance, has been positively associated with cervical cancer screening, earlier stage at diagnosis, receipt of guideline-based therapy, and improved survival.”

    Or further: “An evaluation of three interventions to increase cervical cancer screening rates in a multi-ethnic sample found that having private insurance and/or a usual source of care were the strongest predictors of cervical cancer screening behavior.”

    Of course, the study starts out by saying: “Screening conducted every 3 years among women aged 20 to 64 reduces the cumulative incidence of ICC by 91% according to data from the U.S. Preventive Services Task Force.”

    This all fully supports the Bach quote that used the reference: “Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective.” Again, I’ll repeat my original assertion, it reduces BOTH disease and mortality, NOT only mortality as Julian Frost suggested.

    @Julian Frost “A pap smear detects the disease in the early stages where treatment is cheapest and most likely to be effective. However, it’s still more expensive than the vaccination. The ROI still favours the vaccine.”

    To keep insisting that in the face of evidence to the contrary is pretty illogical. I’m sure the authors of the financial model would be happy to address the concerns of Julian Frost based on the fact that “he says so”.

    @JGC “As for Bach’s claims that ineffective delivery making the program economicallu unattractive, that’s again not an argument against immunization–it’s an argument in favor of optimizing the delivery program.”

    Bach does make the argument for better delivery, but the argument for cancellation is also valid for consideration. In post #565 I raised this to point out how marginal the ROI was for the whole program, and that given the failure of distribution it was providing negative ROI.

    @JGC “Regular pap screening is capable only of detecting cervical cancer once it arises, while immunization prevents its occurrence. Would you similarly argue that there’s no need to expend resources preventing the sale of guns to convicted felons, long as we can accurately determine after the fact when a felon has purchased a firearm?”

    Not true. Pap smears with proper followup is a preventative measure which reduces the incidence of ICC (invasive cervical cancer). “Screening conducted every 3 years among women aged 20 to 64 reduces
    the cumulative incidence of ICC by 91% according to data from the U.S. Preventive Services Task Force.”
    (Akers AY, Newmann SJ, Smith JS. Factors underlying disparities in cervical cancer incidence, screening, and treatment in the United States. Curr Probl Cancer 2007; 31: 157–81.) That’s why the ROI on the vaccine is so marginal and is also highly sensitive to several factors including efficacy and length of immunity.

    @Shay “Yes, JCG gets it…you, on the other hand, don’t.”

    That’s ironic coming from the person who inferred that the cost of preventing a case of cervical cancer is $300 based on vaccination. You’re only off by a couple of orders of magnitude on that one.

  66. #66 Mr Pink
    March 6, 2013

    @Krebiozen

    “Which is progress of sorts.”

    Thanks for pointing out my ommision: “The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money by their own calculations. Hopefully they can clean up their early failure.”

    ” I am not alone in thinking it might be possible to eradicate HPV eventually.”

    All he did was say that it was theoretically possible but he doesn’t express any confidence in it. He can’t even forsee a future where screening is not required. You might note that he also confirms that screening requirements won’t change based on the current vaccines. That borders on magical.

    “One more thing – I was getting HPV testing confused with HPV antibody testing earlier. Testing for HPV is considerably more sensitive than cytology though less specific. There’s a recent paper on the future of cervical cancer screening here if anyone’s interested. It concludes: “It is entirely conceivable that women will no longer die from cervical cancer in the near future, thanks to global effective screening and preventive efforts through widespread HPV vaccination.””

    The expert you noted above was also quite vehement that screening was required to eliminate the incidence of cervical cancer.

    I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination.

    Thank you very much for making that point crystal clear for all to see.

    One last thought for you: Since the vaccine will only prevent some of the incidence of cancer (certain strains), your quote above implies that the screening will be 100% effective for the rest. Why do you suppose that screening wouldn’t be as effective for vaccine strains? Cognitive dissonance anyone?

  67. #67 Mr Pink
    March 6, 2013

    CORRECTION:
    I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has NO competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination.

  68. #68 Narad
    March 6, 2013

    Pink, do you recall saying this?

    Cervical cancer is primarily a disease of the poor. In the US, the cervical cancer mortality rates in the poor states can be double that of the wealthy ones. The cost justification of the program assumes that the poor get the vaccine…. Unfortunately health care distribution in the US is skewed to the wealthy and the vaccine distribution is the same making calling into question the cost justification.

    Now, do you remember this?

    Overall, Blacks and non-Hispanic whites have been noted to have the highest cervical cancer screening rates among all ethnic groups….

    Black in America directly correlates with lower socioeconomic status. (Nationwide, however, there is a slight disproportionality toward Whites in Medicaid coverage.)

    Now, please explain the figure within the framework of your reasoning. You are plainly arguing against Gardasil, now with a slapdash economic construction, but what are you arguing for?

  69. #69 Narad
    March 6, 2013

    Blockquote faiil. I take it that what’s what is discernible.

  70. #70 Narad
    March 6, 2013

    I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs.

    Are you insane? You think that “community hospitals” are going to start performing some weird-ass nested PCR?

  71. #71 Narad
    March 6, 2013

    Moreover, what does this even have to do with HPV screening? As you may recall, Lee’s “technology” is for detecting deadly Gardasil DNA brain residues.

  72. #72 Narad
    March 6, 2013

    Oh, right, I forgot that he’s selling it by way of “SaneVax”:

    Submit the specimen or its residues (at least 5% of the original collection) in a Cytyc or SurePath liquid-based cytology vial in a small zip-lock bag with this requisition in a padded envelope…. Specimens without a valid SaneVax No. will not be processed.

    The point remains elusive.

  73. #73 Julian Frost
    NOYDB
    March 7, 2013

    @Mr Pink:
    “A pap smear detects the disease in the early stages where treatment is cheapest and most likely to be effective. However, it’s still more expensive than the vaccination. The ROI still favours the vaccine.”
    To keep insisting that in the face of evidence to the contrary is pretty illogical. I’m sure the authors of the financial model would be happy to address the concerns of Julian Frost based on the fact that “he says so”.
    It’s not just I who says so.
    Cost of treating early -stage cancer: $ 7,370.
    Cost of the jab: $360.
    Source (PDF): http://www.michigancancer.org/pdfs/mdchfactsheets/cervcainmichfact%20sheet-jan07.pdf
    The maths says that 20 Gardasil vaccinations are cheaper than one early-stage treatment. But introduce the fact that HPV has been implicated in numerous other cancers and the ROI is even better.
    It’s still cheaper to vaccinate.

  74. #74 Julian Frost
    NOYDB
    March 7, 2013

    Please bring back the edit button.

  75. #75 herr doktor bimler
    March 7, 2013

    Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has NO competition

    This seems to be Mr Pink’s response to my penultimate comment (#641) –a link to a press release from Lee and SaneVax in which they complain about the existence of competition.

  76. #76 flip
    March 7, 2013

    @Narad

    You are plainly arguing against Gardasil, now with a slapdash economic construction, but what are you arguing for?

    Dr Lee is awesomesauce, quite obviously.

  77. #77 Narad
    March 7, 2013

    This seems to be Mr Pink’s response to my penultimate comment (#641) –a link to a press release from Lee and SaneVax in which they complain about the existence of competition.

    If only they would glom onto fan death. (Yes, I know, wrong nationality, but still.)

  78. #78 Krebiozen
    March 7, 2013

    Mr. Pink,

    Thanks for pointing out my ommision: “The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money by their own calculations. Hopefully they can clean up their early failure.”

    You have moved from suggesting that, “people should avoid Gardasil”, to complaining that the problem is the CDCs failure to vaccinate enough people. Who was it that mentioned cognitive dissonance?

    ” I am not alone in thinking it might be possible to eradicate HPV eventually.”

    All he did was say that it was theoretically possible but he doesn’t express any confidence in it. He can’t even forsee a future where screening is not required. You might note that he also confirms that screening requirements won’t change based on the current vaccines. That borders on magical.

    Did you read the article I linked to at #628?

    “There are new vaccines being planned that will vaccinate against nine types. If they are successful, there should be no need to screen women that have been vaccinated at all. That’s the long-term future: vaccination and no screening. After about 50 years, we could see cervical cancer disappearing”.

    That seems pretty confident to me, about an eventual end to screening too. How does expecting the polyvalent vaccines currently undergoing clinical trials and the antiviral treatment for HPV currently under development to be successful even border on “magical thinking”?

    The expert you noted above was also quite vehement that screening was required to eliminate the incidence of cervical cancer.

    Where have I ever suggested that it would not be? If you are so concerned about the costs, look at them over the very long-term when HPV and cervical cancer have been eradicated and there is no longer any need for screening, treatment and, ultimately, vaccination. How much would smallpox have cost over the last 35 years if it hadn’t been eradicated?

    One last thought for you: Since the vaccine will only prevent some of the incidence of cancer (certain strains), your quote above implies that the screening will be 100% effective for the rest. Why do you suppose that screening wouldn’t be as effective for vaccine strains? Cognitive dissonance anyone?

    You appear to have an odd habit of rigid black and white thinking. I am suggesting that neither vaccination nor screening would be 100% effective on their own, but together with technologies currently being developed they could result in HPV eradication. Even if efforts to achieve this “pipe dream” fail, they can be expected to result in a dramatic fall in incidence of cervical cancer.

  79. #79 Krebiozen
    March 7, 2013

    Missed an apostrophe in “CDC’s”. Better than a superfluous one, but I isn’t illiterate, honest.

  80. #80 Julian Frost
    NOYDB
    March 7, 2013

    @Krebiozen:

    How much would smallpox have cost over the last 35 years if it hadn’t been eradicated?

    I read somewhere (don’t remember) that the elimination of smallpox pays for itself every 26 days. So, billions of dollars would be my guess.

  81. #81 LW
    March 7, 2013

    Mr Pink’s reasoning seems to be that poorer women are less likely to get regular screening for cervical cancer, therefore there is no reason for then to be vaccinated since that would only reduce the number of cancers that they aren’t being screened for.

    Do I have that right?

  82. #82 Shay
    March 7, 2013

    That’s ironic coming from the person who inferred that the cost of preventing a case of cervical cancer is $300 based on vaccination. You’re only off by a couple of orders of magnitude on that one.

    That’s ironic coming from someone who keeps using “ROI” and “orders of magnitude” with no indication you understand what they mean.

    As has been pointed out already, you have shifted your argument from Gardasil doesn’t work to other things work better and besides it’s too expensive. Citations needed, as what you have provided so far doesn’t support your argument.

    (Pap smears as a cancer treatment. Hoo, boy).

  83. #83 Renate
    March 7, 2013

    Cookie please.

    Still waiting for mr. or mrs Floyd in addition to mr. Pink.

  84. #84 Denice Walter
    March 7, 2013

    @ LW:

    I might argue the reverse: they need it more because they can’t access screening.
    But then, that’s just me.

  85. #85 Lawrence
    March 7, 2013

    I don’t understand the reasoning here – since pap smears & even testing doesn’t actually prevent cervical cancer………yet the vaccine does prevent the disease (so people who don’t have access to screening or just don’t screen, are less likely to get cervical cancer in the first place).

    Mr. Pink – care to explain what the hell you’re talking about? Because if there was a vaccine against breast cancer, it sounds like you’d be arguing that more mammograms would be better than prevention…….

  86. #86 LW
    March 7, 2013

    @Denise Walter, “I might argue the reverse: they need it more because they can’t access screening.  But then, that’s just me.”

    That’s what you think. It’s what I think too. But it doesn’t seem to be what Mr Pink thinks. 

  87. #87 Krebiozen
    March 7, 2013

    While pondering this I found something interesting, from a 2008 article, ‘The World Health Organization and global smallpox eradication’

    Strikingly, not all public health and medical officials were supportive of smallpox eradication, as many considered the goal an impossible one and, therefore, a misguided waste of scarce resources.

    The World Health Assembly Resolution WHA11.54, an undertaking to eradicate smallpox globally was accepted in 1959. The last case of wild smallpox was in 1977. I’m not saying that HPV can be eradicated in less than 20 years, but without the vision and determination shown by public health officials (and many others), we would still be seeing millions dying from smalllpox.

  88. #88 Krebiozen
    March 7, 2013

    Another interesting (to me, anyway) snippet of history, from a review of ‘Smallpox—The Death of a Disease: The Inside Story of Eradicating a Worldwide Killer’ by D. A. Henderson, the sacrificial lamb described here:

    Because the WHO director-general believed that eradication was impossible, he insisted on putting an American in charge so that when the program failed, the United States would be held responsible for the debacle. Henderson was chosen as the sacrificial lamb, and in October 1966, aged 39 and with only 10 years of experience in public health, he flew to Geneva to lead what looked to be a quixotic effort.

    I’d say the WHO DG shot himself in the foot.

  89. #89 Mr Pink
    March 8, 2013

    @Lawrence “I don’t understand the reasoning here – since pap smears & even testing doesn’t actually prevent cervical cancer………yet the vaccine does prevent the disease (so people who don’t have access to screening or just don’t screen, are less likely to get cervical cancer in the first place).
    Mr. Pink – care to explain what the hell you’re talking about? Because if there was a vaccine against breast cancer, it sounds like you’d be arguing that more mammograms would be better than prevention…….”

    Lawrence, this isn’t my argument, it’s the argument of the evidence I’m quoting. Read the Akers reference I provided in post #665. Screening (pap tests) and followup reduces the INCIDENCE of cancer by an average of 91%. Good screening is even more effective at reducing the incidence of the disease. The vaccine is projected (since it hasn’t be shown to reduce any cancer yet) to reduce the incidence of cancer. Since the vaccine only covers several strains, the experts all recommend implementing the best screening available (which consists of HPV genotyping) to reduce the incidence of cancer caused by non vaccine strains. There is a huge overlap between pap tests and the vaccines, in that they both prevent the same types of cancer. The difference is that screening actually prevents cancer from all strains, while the vaccine is theoretically supposed to prevent a few more cases of vaccine strains only. But even this conclusion is dubious because the better screening which is available today (HPV genotyping) will further improve the rates of screening and prevention. At that point, the few extra cases vaccination might theoretically prevent, will only come true if the most optimisitic assumptions of efficacy and 100% lengevity are true. The early population data comparing vaccinated and unvaccinated populations in real life (2012 Athena study) gives us a hint that the vaccine prevents only a few percent of infections which is a huge deviation from the efficacy estimates.

    If the strategy seems confusing — confusing is a generous word IMO — it’s because it doesn’t make a whole lot of sense unless you’re the one selling the vaccine.

    @narad “Are you insane? You think that “community hospitals” are going to start performing some weird-ass nested PCR?”

    Just because you don’t understand it doesn’t mean it’s weird or complicated. The heavily downloaded article describes both the methods and the efficacy show that there is quite a bit of interest and others get it even if you don’t.

    @narad “Now, please explain the figure within the framework of your reasoning. You are plainly arguing against Gardasil, now with a slapdash economic construction, but what are you arguing for?”

    Are you dense? Re-read #665. Your graph is followed by the revelation that the correlation disappears when confounding factors are corrected. Bach’s reference of Ackers et al is completely valid.

    @LW “Mr Pink’s reasoning seems to be that poorer women are less likely to get regular screening for cervical cancer, therefore there is no reason for then to be vaccinated since that would only reduce the number of cancers that they aren’t being screened for. Do I have that right?”

    No you do not. Denice has it right. The vaccine was designed primarily for treatment of the developing world and people who do not have access to good screening and followup. Read Ian Frazer’s quotes. He’s the guy who kicked the whole thing off and he did it for the developing world (God’s gift to women: The HPV vaccine). The Bach reference describes that the US program is inefficient (i.e. won’t be cost effective) because it’s vaccinating the women who need the vaccine the least (those with access to good screening and followup). There is a correlation between low average income and low vaccine uptake by state. That means that the people who need the vaccine the most (i.e. the ones for whom it is most cost effective) aren’t getting it. That’s the failure of the US vaccine program by it’s own measured objectives. Read the Bach reference for more details. According to Bach, the failure is even more embarrassing because it was predicted prior to the start of the program.

    @Shay “As has been pointed out already, you have shifted your argument from Gardasil doesn’t work to other things work better and besides it’s too expensive. Citations needed, as what you have provided so far doesn’t support your argument.”

    I did not shift my argument. I made three independent ones. My first argument is that Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes. A second argument is that even using the most ROSY projections (from the reference I provided), the vaccine program in the United States has a negative ROI due to a failure in the delivery system (they have not vaccinated the highest risk populations). A third argument, is that even if the ROSY projections are all true, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.

    I have provided references for those arguments. Your implication that it costs $300 to prevent a case of cervical cancer indicates that it is you who have no clue on the cost justification of the program. I’ll also note that you have not provided a single reference for your fantastical claim. My references start in comment #565. You might actually learn something if you read them.

  90. #90 Mr Pink
    March 8, 2013

    @Krebiozen

    You have moved from suggesting that, “people should avoid Gardasil”, to complaining that the problem is the CDCs failure to vaccinate enough people.

    No, I have provided three independent arguments all of which are valid. My first argument is that Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes. A second argument is that even if we assume it works and use the most ROSY projections (from the reference I provided), the vaccine program in the United States has a negative ROI due to a failure in the delivery system (they have not vaccinated the highest risk populations). A third argument, is that even if we assume it works and the ROSY projections are all true and the delivery failure is corrected, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.

    There is no conflict between those arguments.

    That seems pretty confident to me, about an eventual end to screening too. How does expecting the polyvalent vaccines currently undergoing clinical trials and the antiviral treatment for HPV currently under development to be successful even border on “magical thinking”?

    Really? He says “IF they will be successful”. He doesn’t even indicate if he thinks they will be successful or not. In fact, he follows up with this: “Even for girls vaccinated before this age with the current vaccine, there will be a need for some screening to protect from cancers caused by HPV types not in the vaccine, so screening is here to stay for the foreseeable future.
    He can’t even foresee a future without screening! That doesn’t sound too confident to me.

    Where have I ever suggested that it would not be?

    I didn’t say you suggested it. That sentence led into the next paragraph: “I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination.

    How much would smallpox have cost over the last 35 years if it hadn’t been eradicated?

    Your analogy is invalid. Smallpox is not at all like HPV. If you want to use prior vaccination as evidence, it is far more likely HPV will NOT be eradicated given the vast number of vaccination programs and only 1 successful eradication. I don’t accept an argument based on wishful thinking and no plausible mechanism for success, and neither should you.

    You appear to have an odd habit of rigid black and white thinking. I am suggesting that neither vaccination nor screening would be 100% effective on their own, but together with technologies currently being developed they could result in HPV eradication. Even if efforts to achieve this “pipe dream” fail, they can be expected to result in a dramatic fall in incidence of cervical cancer.

    You misread my argument — now I’m repeating myself. I pointed out the quote from the reference YOU provided states that the combination of vaccination and screen could eliminate cervical cancer: “If vaccination were to be combined with HPV screening (which is much more sensitive than the currently used Pap smear test), then eventually the cancer would disappear in those countries that had successfully implemented national programmes.” It seems you miss a lot of little important details in your own references. Don’t accuse me of being black and white, when I’m actually reading the references you’re providing.

  91. #91 Bill Price
    March 8, 2013

    #686, LW:

    doesn’t seem to be what Mr Pink thinks.

    Objection? Assumes facts not in evidence (that Mr Pink actually thinks).

  92. #92 Narad
    March 8, 2013

    Are you dense?

    I’m a Bose condensate, baby. I am not ionized and I possess not valence. Nothing “disappears.”

  93. #93 LW
    March 8, 2013

    So vaccination doesn’t get to the poorest women in America (even though it’s provided by county health departments) but instead of implementing a better vaccination program what we should do is to provide *much* more screening, including piping plenty of work to Dr Lee.

  94. #94 Krebiozen
    March 8, 2013

    Mr. Pink,

    My first argument is that Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes.

    That’s not an actual argument, is it? I agree that “Gardasil has no demonstrated efficacy against the target endpoint” for the reasons you list and that we have discussed ad nauseam. My argument is that it is perfectly reasonable to expect Gardasil to demonstrate efficacy against the target endpoint, invasive cervical cancer, in the long term because (i) Gardasil prevents HPV-16 and HPV-18 in those not already infected, (ii) HPV infection is a necessary precursor of all, or almost all, CIN (and AIS) and cervical cancer and (iii) treating those surrogate outcomes (CIN and AIS) prevents invasive cervical cancer (as you yourself have pointed out). There is a large body of evidence that supports all three of these assertions.

    A second argument is that even if we assume it works and use the most ROSY projections (from the reference I provided), the vaccine program in the United States has a negative ROI due to a failure in the delivery system (they have not vaccinated the highest risk populations).

    Again, I don’t see an actual argument. The vaccine has a negative ROI due to poor delivery therefore what? We should throw up our hands in despair and abandon HPV vaccination entirely? Or should we make efforts to improve vaccine delivery to those who need it the most? Personally I am in the UK so the CDC’s failings don’t matter as much to me as the NHS’s implementation of Gardasil (now replacing Cervarix) which is going very well.

    The same goes for the fact that Gardasil protects mostly against 70% of the cancer-causing strains. That’s an argument for polyvalent vaccines, not against vaccination.

    A third argument, is that even if we assume it works and the ROSY projections are all true and the delivery failure is corrected, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.

    At last an actual argument! I agree that you could argue that the money might be better spent elsewhere, though I (and public health authorities around the world) disagree with you. As I pointed out somewhere above, public health is fraught with uncertainty and is always a gamble to some extent; it is very rare, if it ever occurs, that you have hard evidence to definitively prove what the outcome of public health measures will be in the long term, and the unexpected does sometimes occur. That’s one reason I find public health so interesting.

    BTW, as I have also pointed out, there is more to preventing disease than ROI. The way you equate a case of CIN or AIS treated surgically with one prevented by vaccination suggests you don’t quite appreciate this.

    There is no conflict between those arguments.

    The only actual argument I can see there is about cost efficacy. You did initially suggest that “people should avoid Gardasil”, and you do now appear to be suggesting that the problem with Gardasil is that too few, not too many, are getting it. Perhaps you would like to clarify your position..

    That seems pretty confident to me, about an eventual end to screening too. How does expecting the polyvalent vaccines currently undergoing clinical trials and the antiviral treatment for HPV currently under development to be successful even border on “magical thinking”?

    Really? He says “IF they will be successful”. He doesn’t even indicate if he thinks they will be successful or not. In fact, he follows up with this: “Even for girls vaccinated before this age with the current vaccine, there will be a need for some screening to protect from cancers caused by HPV types not in the vaccine, so screening is here to stay for the foreseeable future.” He can’t even foresee a future without screening! That doesn’t sound too confident to me.

    There’s that black and white thinking again. I originally wrote, “in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated”. You claimed this is “a pipe dream” i.e. that it is impossible, equivalent to a drug-induced delusion. It is quite clear that Professor Cuzick agrees with me. What do you think he meant by, “That’s the long-term future: vaccination and no screening”?

    Where have I ever suggested that it would not be?

    I didn’t say you suggested it. That sentence led into the next paragraph: “I will point out now that Dr Lee’s technology provides […]

    I see, so it was just a non sequitur you used as an excuse for plugging Dr Lee’s products.

    How much would smallpox have cost over the last 35 years if it hadn’t been eradicated?

    Your analogy is invalid. Smallpox is not at all like HPV. If you want to use prior vaccination as evidence, it is far more likely HPV will NOT be eradicated given the vast number of vaccination programs and only 1 successful eradication.

    It wasn’t intended as an analogy, it is an example of how public health measures can have very much greater ROI over the long term than they do in the short term. Clearly smallpox and HPV are very different and strategies to eradicate HPV will differ greatly from those that succeeded with smallpox. I don’t see that as a reason not to attempt it, especially when the most likely outcome, even if we fail, is a large reduction in morbidity and mortality.

    I don’t accept an argument based on wishful thinking and no plausible mechanism for success, and neither should you.

    My argument was that “in the future we may be able to […] eliminate HPV” (my emphasis). That is based on the development of polyvalent vaccines that already exist and are going through clinical trials, screening technologies that already exist and antiviral drugs that are under development. Those are extremely plausible mechanisms, not wishful thinking.

    You appear to have an odd habit of rigid black and white thinking. I am suggesting that neither vaccination nor screening would be 100% effective on their own, but together with technologies currently being developed they could result in HPV eradication. Even if efforts to achieve this “pipe dream” fail, they can be expected to result in a dramatic fall in incidence of cervical cancer.

    You misread my argument — now I’m repeating myself. I pointed out the quote from the reference YOU provided states that the combination of vaccination and screen could eliminate cervical cancer: “If vaccination were to be combined with HPV screening (which is much more sensitive than the currently used Pap smear test), then eventually the cancer would disappear in those countries that had successfully implemented national programmes.”

    I don’t follow your argument here. To clarify this, what you wrote was:

    Since the vaccine will only prevent some of the incidence of cancer (certain strains), your quote above implies that the screening will be 100% effective for the rest. Why do you suppose that screening wouldn’t be as effective for vaccine strains? Cognitive dissonance anyone?

    A minor niggle, the “quote above” you referred to was actually:

    “It is entirely conceivable that women will no longer die from cervical cancer in the near future, thanks to global effective screening and preventive efforts through widespread HPV vaccination.””

    Not, “If vaccination were to be combined with HPV screening (which is much more sensitive than the currently used Pap smear test), then eventually the cancer would disappear in those countries that had successfully implemented national programmes.” The current vaccine doesn’t cover all cancer-causing strains, but future vaccines will. Testing for HPV is considerably more sensitive than pap screening but it is less specific. Clearly eradication will require an ongoing and responsive strategy as progress against HPV is made.

    It seems you miss a lot of little important details in your own references. Don’t accuse me of being black and white, when I’m actually reading the references you’re providing.

    It is possible I have missed some details, as I waded through most of the HPV vaccine literature a couple of years ago and have only skimmed through them to refresh my memory more recently. However, you do appear to have a habit of focusing on unimportant details while missing the bigger picture.

  95. #95 Shay
    March 8, 2013

    A third argument, is that even if the ROSY projections are all true, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.

    Taking into consideration that in the US, public health ROIs are outcome-based, not revenue-based, what other program offers a better ROI with regard to protection against HPV?

  96. #96 Mr Pink
    March 8, 2013

    @LW “So vaccination doesn’t get to the poorest women in America (even though it’s provided by county health departments) but instead of implementing a better vaccination program what we should do is to provide *much* more screening, including piping plenty of work to Dr Lee.”

    Don’t take my word for it. The latest stats (at the CDC) show some improvement in overall coverage, but there is still a large disparity between the states. As for screening, just follow the expert recommendations. Krebiozen linked to one expert. Ackers et al says the same thing. Improved screening based on HPV genotyping is pretty much a unanimous recommendation. WRT Dr Lee, you don’t seem to understand the technology or the motives. Dr Lee doesn’t want the work, he wants it to be done at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more.

    @Shay “Taking into consideration that in the US, public health ROIs are outcome-based, not revenue-based, what other program offers a better ROI with regard to protection against HPV?”

    I’m not sure where you are getting your definitions. Check out slide 12. http://works.bepress.com/cgi/viewcontent.cgi?article=1083&context=glen_mays
    HPV screening (vs pap tests) is universally recommended and has a very high ROI.

  97. #97 Mr Pink
    March 8, 2013

    @Krebiozen

    That’s not an actual argument, is it?

    It was originally stated in the context of your original assertion and you argued against it in post 525. “Disingenous nonsense (PDF)”.

    My argument is that it is perfectly reasonable to expect Gardasil to demonstrate efficacy against the target endpoint, invasive cervical cancer, in the long term because (i) Gardasil prevents HPV-16 and HPV-18 in those not already infected, (ii) HPV infection is a necessary precursor of all, or almost all, CIN (and AIS) and cervical cancer and (iii) treating those surrogate outcomes (CIN and AIS) prevents invasive cervical cancer (as you yourself have pointed out).

    I have summarized the issues with your assumptions:
    i) You are relying on historically unreliable regulatory studies AND the initial real population data differs significantly
    ii) Most CIN2 (which is the only outcome they actually measured) regresses naturally. You don’t know why some small number of cases progress so you can’t assume those cases would have been vaccine preventable.
    iii) Treatment of CIN2 has no bearing on your argument. Like I said in ii) it’s not a good surrogate.

    Again, I don’t see an actual argument.

    In post #547, you stated: “Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality.” My response is an argument against that now proven ridiculous assumption from a public health perspective. However, I can also independently make the argument that Public Health is wasting money on the program and that is the supporting point.

    Personally I am in the UK so the CDC’s failings don’t matter as much to me as the NHS’s implementation of Gardasil (now replacing Cervarix) which is going very well.

    You make the statement but bring no evidence to the table. Who is at greatest risk in the UK (i.e. those that aren’t taking advantage or getting good screening and followup) and are they getting the vaccine? You own public health’s decision to originally go with Ceravix is baffling — unless you consider who was selling it of course — to say the least so I hardly have confidence they’re making any good decisions. I also understand that NHS has bungling some VERY expensive programs over the past few years, so trusting them to spend your money wisely is hardly a good choice.

    As I pointed out somewhere above, public health is fraught with uncertainty and is always a gamble to some extent; it is very rare, if it ever occurs, that you have hard evidence to definitively prove what the outcome of public health measures will be in the long term, and the unexpected does sometimes occur.

    Yes, you talked about gambles early on. You sound more like a wealth manager selling someone on an IPO of a new company that has no history or background. Even worse, your best case scenario is an outcome that is so narrowly positive that there is no contingency. That’s a bad gamble in most books.

    That’s one reason I find public health so interesting.

    Your being the UK lends some insight into why you seem argue for public health decisions without consideration of cost. In the UK you have a heavily funded public programs and people often forget that it’s coming out of your taxes. I won’t even go into the money the NHS wastes.

    BTW, as I have also pointed out, there is more to preventing disease than ROI. The way you equate a case of CIN or AIS treated surgically with one prevented by vaccination suggests you don’t quite appreciate this.

    I certainly do. You brought up the topic of public health, and they should be making decisions based on data, not emotion. One of the most important constraints in public health is money. To continually complain about it is baffling.

    The only actual argument I can see there is about cost efficacy. You did initially suggest that “people should avoid Gardasil”, and you do now appear to be suggesting that the problem with Gardasil is that too few, not too many, are getting it. Perhaps you would like to clarify your position..

    My position has not changed. On an individual basis, one should focus on screening since it is universally recommended. I would not recommend the vaccine because it has no demonstrated efficacy for cancer, and if you have good screening, the vaccine will at best theoretically reduce your risk a couple of percent and only if the regulatory data holds true in real life (which it never does). Public health should stay away since it’s not cost effective and the money better spent elsewhere.

    You claimed this is “a pipe dream” i.e. that it is impossible, equivalent to a drug-induced delusion. It is quite clear that Professor Cuzick agrees with me. What do you think he meant by, “That’s the long-term future: vaccination and no screening”?

    “Pipe dream” is not incongruent with “not in the foreseeable future” or “wishful thinking”.

    I see, so it was just a non sequitur you used as an excuse for plugging Dr Lee’s products.

    No, it was an observation based on your reference.

    Clearly smallpox and HPV are very different and strategies to eradicate HPV will differ greatly from those that succeeded with smallpox. I don’t see that as a reason not to attempt it, especially when the most likely outcome, even if we fail, is a large reduction in morbidity and mortality.

    We already have a very effective way to reduce mortality and morbidity thanks to improved screening. In a way you’re right, relying on a deux ex machina is reason enough not to attempt eradication so we don’t have to bother talking about smallpox.

    Those are extremely plausible mechanisms, not wishful thinking.

    It’s the quarantine part which requires the wishful thinking as you already acknowledged. Vaccination is only one half of the equation as you well know.

    The current vaccine doesn’t cover all cancer-causing strains, but future vaccines will. Testing for HPV is considerably more sensitive than pap screening but it is less specific. Clearly eradication will require an ongoing and responsive strategy as progress against HPV is made.

    Neither statement was predicated on future vaccines. Screening is here to stay for the foreseeable future and still he thinks mortality can be eliminated with the technology we have today. That means that screening is expected to be highly effective and we already know it works for all strains.

    However, you do appear to have a habit of focusing on unimportant details while missing the bigger picture.

    If, treating cost as a key constraint in public health, basing decisions on real evidence of desired endpoints, and making assumptions based on known technology, is considered small thinking, then I guess we’ll just have to leave the big stuff to wishful thinkers like you.

    If you were in the US, I’d say enjoy your March break.

  98. #98 Narad
    March 9, 2013

    Dr Lee doesn’t want the work, he wants it to be done at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more.

    Have you ever been to the type of facility to which you refer? I sorely doubt that you’re based in the U.S.

  99. #99 Narad
    March 9, 2013

    I’m not sure where you are getting your definitions. Check out slide 12. http://works.bepress.com/cgi/viewcontent.cgi?article=1083&context=glen_mays
    HPV screening (vs pap tests) is universally recommended and has a very high ROI.

    Are you fυcking kidding? This gruel, which has nothing whatever to do with HPV anywhere, is the best you can muster?

  100. #100 Krebiozen
    March 9, 2013

    Mr. Pink,

    That’s not an actual argument, is it?

    It was originally stated in the context of your original assertion and you argued against it in post 525. “Disingenous nonsense (PDF)”.

    There is a significant difference between, “There isn’t an ounce of quality evidence showing the vaccine has or will ever reduce the incidence of cervical cancer” (my emphasis) which is what I was arguing against, and “Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes.”

    I have summarized the issues with your assumptions:
    i) You are relying on historically unreliable regulatory studies AND the initial real population data differs significantly

    So we can’t believe the studies that show Gardasil is almost 100% effective at preventing HPV-16 and 18 in those not already exposed? Any particular reason why? There is barely any real population data yet – the study you mentioned above looked at 1000 women who were too old to have been given Gardasil at age 12 so we can’t come to any conclusions based on that.

    ii) Most CIN2 (which is the only outcome they actually measured) regresses naturally. You don’t know why some small number of cases progress so you can’t assume those cases would have been vaccine preventable.

    That’s a strange reverse logic. HPV infection is recognized as the immediate and necessary precursor of all (or almost all) cases of invasive cancer, therefore preventing HPV infection must prevent invasive cancer. The fact that not all HPV infections progress to cancer doesn’t mean that not all cervical cancer started as HPV infection.

    iii) Treatment of CIN2 has no bearing on your argument.

    So you are arguing that treating CIN2 surgically prevents cervical cancer, but preventing CIN2 occurring in the first place with a vaccine does not? That makes no sense at all. I could paraphrase what you wrote above to, “You don’t know why some small number of cases progress so you can’t assume those cases would have been treatment preventable” which would be equally nonsensical. As I have stated before, if there is some small group of women in whom vaccination is ineffective and in whom HPV is more likely to cause cancer, reducing the prevalence of HPV infection will reduce the chances of them becoming infected, and therefore their chances of getting cancer, through the herd efffect.

    Like I said in ii) it’s not a good surrogate.

    It’s not a good surrogate for treatment, as you will end up treating too many women whose CIN would not have progressed to cancer, but if you prevent CIN you will prevent cancer.

    In post #547, you stated: “Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality.” My response is an argument against that now proven ridiculous assumption from a public health perspective.

    It’s not a “now proven ridiculous assumption” at all. It depends on what economic model you use, what time frame you look at, what assumptions you make and what you set as a threshold for cost effectiveness. This review of cost effectiveness found (ICER is incremental cost-effectiveness ratios and QALY is quality-adjusted life year):

    Each model produced a range of cost-effectiveness ratios, dependent on variables included in sensitivity analyses and model assumptions. Sensitivity analyses revealed the lowest ICER to be $997 per QALY gained and the highest ICER to be $12,749,000 per QALY gained. This enormous range highlights the need to clarify what model assumptions are being made.

    If Gardasil costs less than $1,000 per QALY my “now proven ridiculous assumption” is definitely true, since even $2,000 per QALY would make Gardasil extraordinarily good value for money. If it costs more than $12 million per QALY, not so much. As I wrote before it’s arguable. In every area of this arena there is a great deal of uncertainty, and very little is definitively proven at all.

    However, I can also independently make the argument that Public Health is wasting money on the program and that is the supporting point.

    You have made that argument and I, and apparently most of the world’s public health authorities, disagree with you.

    Personally I am in the UK so the CDC’s failings don’t matter as much to me as the NHS’s implementation of Gardasil (now replacing Cervarix) which is going very well.

    You make the statement but bring no evidence to the table.

    It isn’t exactly difficult to find. Here’s some data (PDF) that shows better than 80% average uptake of 3 doses of vaccine in 12-13 year-old girls in 2008/9. More recent data is similar.

    Who is at greatest risk in the UK (i.e. those that aren’t taking advantage or getting good screening and followup) and are they getting the vaccine?

    Most younger girls are vaccinated in schools, so delivery is very effective. From the link above:

    For the routine cohort, 94.2% of 12-13-year-olds were vaccinated in school (see figure 1). For the 17-18-year-old catch-up cohort a more mixed approach was taken by PCTs – 31.4% were vaccinated in the school setting, 60% in GP practices and 8.6% in community clinics and other settings (see figure 2).

    Uptake of cervical screening remains high with about 80% of women being screened every 3 or 5 years as appropriate – I won’t link to the data as it will put this into moderation, but I’m sure you can find it easily enough. I agree with you about some poor decisions made by the NHS, but I don’t think that introducing HPV vaccines is one of them.

    Yes, you talked about gambles early on. You sound more like a wealth manager selling someone on an IPO of a new company that has no history or background.

    I’m excited about HPV vaccines: I think the technology is extraordinary, the efficacy impressive and the safety record remarkable. For the first time ever we have a vaccine that looks very likely indeed to prevent a common cancer. Of course there will be many obstacles to overcome in reducing and ultimately eradicating HPV, but I find your (and others’) negative attitude about such a powerful tool to pursue this goal incomprehensible.

    Even worse, your best case scenario is an outcome that is so narrowly positive that there is no contingency. That’s a bad gamble in most books.

    My best case scenario is global eradication of HPV, cervical and other related cancers. That’s “narrowly positive”?

    Your being the UK lends some insight into why you seem argue for public health decisions without consideration of cost. In the UK you have a heavily funded public programs and people often forget that it’s coming out of your taxes. I won’t even go into the money the NHS wastes.

    Since I have spent several decades working for the NHS, and continually trying to do more with ever dwindling annual budgets, as well as paying taxes that pay for it, I am very well aware of how it works. You could argue that value for money is even more important here, as it is public money that will be saved on the treatment of CIN, AIS, cervical and other cancers if the vaccine program is successful. In the US it is mostly individuals and insurance companies who will have to foot the bill, or not.

    You brought up the topic of public health, and they should be making decisions based on data, not emotion. One of the most important constraints in public health is money. To continually complain about it is baffling.

    You are the one complaining! I’m quite happy with the introduction of Gardasil and the pharmacoeconomic models that decision has been based on. It is you who seems to think that it is better for a woman to be treated for CIN or AIS than it is to prevent her from getting it in the first place.

    My position has not changed. On an individual basis, one should focus on screening since it is universally recommended.

    There we agree, though that may change when HPV becomes less common.

    I would not recommend the vaccine because it has no demonstrated efficacy for cancer, and if you have good screening, the vaccine will at best theoretically reduce your risk a couple of percent and only if the regulatory data holds true in real life (which it never does).

    You would seriously advise the parent of a 12-year-old girl (or boy) against her (or him) having Gardasil? You really think that preventing invasive cancer through surgery is just as good as never getting CIN at all? That’s incomprehensible to me, unless you buy into the sort if misinformation SaneVax propagates, and you seem too well informed to swallow that nonsense.

    Public health should stay away since it’s not cost effective and the money better spent elsewhere.

    “Pipe dream” is not incongruent with “not in the foreseeable future” or “wishful thinking”.

    You can play with semantics all you like, Prof. Cuzick still clearly agrees with me, not you.

    We already have a very effective way to reduce mortality and morbidity thanks to improved screening.

    CIN and AIS count as morbidity, even if successfully treated. Even the most improved screening does not prevent them. Which is better, the vaccine or cervical ablation/excision? If I were a woman I know which I would prefer, even at $120 a shot..

    It’s the quarantine part which requires the wishful thinking as you already acknowledged. Vaccination is only one half of the equation as you well know.

    If vaccination uptake in 12-year-olds is high enough, we will have a generation in which HPV-16 and 18 will be rare. If polyvalent vaccines are introduced, other strains will also become rare. If antiviral drugs targeting HPV are successful they will become even rarer, and eradication will become a real possibility. As has been noted, because of its mode of transmission you don’t really need quarantine for HPV, just some way of successfully treating it and/or preventing those infected from infecting others. There are lots of ifs there I grant you, but I still maintain it is a good bet that this gamble will pay off.

    Screening is here to stay for the foreseeable future and still he thinks mortality can be eliminated with the technology we have today. That means that screening is expected to be highly effective and we already know it works for all strains.

    You’re nitpicking, since he stated, “That’s the long-term future: vaccination and no screening” so he clearly doesn’t mean “never” by “the foreseeable future”.

    If, treating cost as a key constraint in public health, basing decisions on real evidence of desired endpoints, and making assumptions based on known technology, is considered small thinking, then I guess we’ll just have to leave the big stuff to wishful thinkers like you.

    Don’t forget those wishful thinking public health authorities in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Iceland, Israel, Ireland, Italy, Kenya, Latvia, Luxembourg, Macedonia, Mexico, Netherlands, New Zealand, Norway, Panama, Portugal, Romania, Slovenia, South Korea, Spain, Sweden, Switzerland, the United Kingdom and the United States 😉

    If you were in the US, I’d say enjoy your March break.

    If you are in the US, consider it reciprocated.

  101. #101 Melissa G
    March 9, 2013

    Arguing that treatment is preferable to vaccine is heartless, and obviously comes from someone who has never had to experience a colposcopy, or the anguish of waiting years to be pronounced free of HPV displasia and its resulting risk of cervical cancer. The emotional cost is very different when it’s your own body you’re arguing about.

    For the record, my son is getting the Gardasil jab when he turns eleven.

  102. #102 herr doktor bimler
    March 9, 2013

    Dr Lee doesn’t want the work, he wants it to be done at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more.

    Dr Lee doesn’t want the work so much, he is trying to shut competitors out:
    http://www.businesswire.com/news/home/20100920005586/en/S.A.N.E.-Vax-Sin-Hang-Lee-MD-Offers
    I particularly like the appeal to patriotism as the reason to shut out the competing laboratory : “NCI Pays a Foreign Laboratory for Similar Testing”.

    “at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more”

    Apparently Milford’s business model involves undercutting the large public hospitals.

  103. #103 Narad
    March 9, 2013

    While we’re at it, one might note that Norma Erickson has flatly asserted that “the human papillomavirus does not cause cervical cancer.”

  104. #104 Mr Pink
    March 9, 2013

    @Melissa G “Arguing that treatment is preferable to vaccine is heartless, and obviously comes from someone who has never had to experience a colposcopy…”

    You have no clue as to my medical history or that of my family. Arguing for universal experimental vaccination where the treatment holds little discernable benefit for the recipient, obviously comes from someone who has never had a child disabled by a vaccine. For the record, none of my boys will ever get any experimental vaccine.

    @Narad “Are you f…ing kidding? This gruel, which has nothing whatever to do with HPV anywhere, is the best you can muster?”

    Your density is showing, that slide talks about ROI measurements and includes a lot more than outcomes as Shay asserted. Why would I need a reference for the HPV screening recommendations, when K and I already discussed them at length?

    @Krebiozen “So we can’t believe the studies that show Gardasil is almost 100% effective at preventing HPV-16 and 18 in those not already exposed? Any particular reason why?”

    Because the efficacy rates in real life are always lower than the rates observed during regulatory trials. Real life and large populations offer up a lot more complicated environments and individuals than controlled studies do. At the most basic level, regulatory studies for this type of pharmaceutical are designed to screen out anyone with any type of known health problem, and that is becoming less and less representative of the general population.

    @Krebiozen “My best case scenario is global eradication of HPV, cervical and other related cancers. That’s “narrowly positive”?”

    Not with the current vaccine it’s not, which is the context from which you took the quote.

    @Krebiozen “You would seriously advise the parent of a 12-year-old girl (or boy) against her (or him) having Gardasil?”

    I would never recommend for anyone to participate in a medical experiment let alone a child. Until the outcomes are actually measured, it’s still an experiment. I don’t think there is enough data to confidently get a safety profile. It takes decades for problems with pharmaceuticals to be recognized and action taken to address them.

    IMO, attempting to eliminate more and more pathogens through brute force strategies is bound for failure and will cause all sorts of unforeseen side effects. Cervical cancer is clearly caused by more than HPV, and those other factors are undoubtedly involved in other serious diseases. I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet, but there shouldn’t be an expectation for everyone to accommodate or fund what amounts to a big experiment.

    @Krebiozen “You could argue that value for money is even more important here, as it is public money that will be saved on the treatment of CIN, AIS, cervical and other cancers if the vaccine program is successful. In the US it is mostly individuals and insurance companies who will have to foot the bill, or not.”

    I agree and I believe your system is way more efficient, but the immense waste from several NHS debacles over the past few years is immensely disappointing. Our fundamental differences appear to be based on how we project the available data and how much faith we have in the system. The source of our bias’ are obvious: You work in the system, whereas I work with it from the outside.

  105. #105 Narad
    March 9, 2013

    I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet

    Oh, great, now we’ve gotten to both sexual and food ritual purity.

  106. #106 Melissa G
    March 9, 2013

    “Little discernable benefit?”… Yeah, we flat-out disagree.

    “Experimental vaccine?” …Yeah, we double-dog-disagree.

    “I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet”… So, you think diet has something to do with cancer? Do tell us all about it, please.

  107. #107 Krebiozen
    March 9, 2013

    Mr. Pink,

    I would never recommend for anyone to participate in a medical experiment let alone a child. Until the outcomes are actually measured, it’s still an experiment. I don’t think there is enough data to confidently get a safety profile. It takes decades for problems with pharmaceuticals to be recognized and action taken to address them.

    We are all participating in a medical experiment of sorts whether we like it or not. If Gardasil was not approved until its impact on invasive cervical cancer had been proven in RCTs the likely result would be that up to 30,000 women would die unnecessarily, and up to 4 million would require treatment for CIN or AIS that could have been prevented. Once an intervention like Gardasil is available, even opting out is an experiment, an experiment which in this case I think puts the child at far greater risk than opting in.

    IMO, attempting to eliminate more and more pathogens through brute force strategies is bound for failure and will cause all sorts of unforeseen side effects.

    Most of the inflammatory diseases we suffer from are due to processes that are designed to protect us against pathogens. Once those pathogens are eliminated, by “brute force” or otherwise, we will inevitably see more diseases on the inflammatory end of the scale, such as cardiovascular diseases, autoimmune disorders, allergies and cancer. That doesn’t mean that our brute force strategies cause the inflammatory problems, just that a century ago little Jimmy would have died of pneumonia but today he survives to get asthma and prostate cancer.

    Cervical cancer is clearly caused by more than HPV, and those other factors are undoubtedly involved in other serious diseases.

    Now I’m bracing myself for Beauchamp or Pasteur’s (bogus) deathbed recantation, “Terrain is everything!” I’m not sure I buy any of the kinds of ideas I think you are hinting at. “Eat, not too much, mostly plants” is about as far as I would go in that direction.

    I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet, but there shouldn’t be an expectation for everyone to accommodate or fund what amounts to a big experiment.

    One thing I think we should have learned about vaccination is that it is an all or nothing venture. When rubella vaccination was introduced in Greece poor vaccine uptake meant that girls who contracted rubella tended to do so later than before vaccination, resulting in more of them getting it when pregnant and an increase in congenital rubella syndrome. That makes vaccines problematic when it comes to personal freedom, and I don’t have any easy answers. When you consider being infected by a virus turns a person into a walking virus manufacture and distribution system, so I think it is reasonable to expect people to take measures to prevent this. How far we should go in coercing people into vaccination, I’m not sure.

    I agree and I believe your system is way more efficient, but the immense waste from several NHS debacles over the past few years is immensely disappointing.

    I agree. I have personally felt extremely frustrated by problems in the NHS, such as the hospital I work for purchasing different incompatible computer systems in different departments, a half-assed internal market, and constantly being kept from doing useful work by being expected to attend pointless meetings. I once was asked to attend a meeting and realized when I got there that I hadn’t the faintest idea what it was about, and spent half the meeting quietly trying to figure it out from what was being discussed (it turned out to be about developing a computerized staff record which was a total waste of my time). Large bureaucracies evolve organically over time into unwieldy and inefficient edifices that don’t resemble anything anyone (except perhaps a committee) would design from scratch. The Peter Principle doesn’t help matters – I have often seen a person good at their job get promoted into a management position that they were utterly incompetent at, where they stayed until they could swing early retirement. I could go on, but I won’t.

    Our fundamental differences appear to be based on how we project the available data and how much faith we have in the system. The source of our bias’ are obvious: You work in the system, whereas I work with it from the outside.

    I do both actually, as a healthcare worker and from time to time as a patient. A couple of times I have felt badly let down by the NHS, which was a very unpleasant experience since I support its principles passionately, and have worked for it for most of my life.

  108. #108 Krebiozen
    March 9, 2013

    I meant to add that my statement, ” up to 30,000 women would die unnecessarily, and up to 4 million would require treatment for CIN or AIS that could have been prevented” is based on an assumption that it would take 10 years to see if invasive cervical cancer is prevented by Gardasil, and refers to the US alone.

  109. #109 LW
    March 10, 2013

    “I would never recommend for anyone to participate in a medical experiment let alone a child.”

    And if we all adopt this attitude, then there will never be any medical experiments at all.

  110. #110 herr doktor bimler
    March 10, 2013

    [romantic story] Participating in a medical experiment was how I met the Frau Doktorin!
    [/ romantic story]

  111. #111 Narad
    March 10, 2013

    [bladder pride story] Hey, participating in a medical experiment is how I set a record for largest urine sample the PET lab had ever encountered (seriously, this was around 1.3 liters). [/bladder pride story]

    In an unrelated development, the fellow behind the absinthe FAQ caused the IRB to take a second look at the experiment (straight fenfluramine), so I was paid for my sessions despite not completing all five.

  112. #112 herr doktor bimler
    March 10, 2013

    Did someone say bladder pride?

  113. #113 Grant
    March 10, 2013

    hdb – I was wondering when you’d link to that 😛

  114. #114 Narad
    March 10, 2013

    Did someone say bladder pride?

    At least I didn’t say rubber biscuit.*

  115. #115 Narad
    March 10, 2013

    * You don’t want to know what was in the deleted footnote anyway.

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