Oh, Discover. You’re such a tease. You have Ed and Carl and Razib and Phil and Sean, an (all-male, ahem) cluster of science bloggy goodness. But then you also fawn over HIV deniers Lynn Margulis and Peter Duesberg. Why can’t you just stick with the science and keep the denial out?*

But no, now they’ve let it spill into their esteemed blogs. I was interested to see a new blog pop up there, The Crux, a group blog “on big ideas in science and how these ideas are playing out in the world. The blog is written by an outstanding group of writer/bloggers and scientist/writers who will bring you the most compelling thoughts throughout the world of science, the stuff most worth knowing.” Sounds ok, let’s see what stories are up…oh, one on HPV! Right up my alley. And hey, a woman! Bonus.

*Reads story*

Ohhhhh, it’s actually one on HPV vaccine misinformation, written by the author of the fawning Duesberg article referenced above. Faaantastic.

The author, Jeanne Lenzer, poses the question, Should boys be given the HPV vaccine? and answers herself that “the science is weaker than the marketing.”

What does she base this conclusion on? A recent paper examining HPV vaccine in boys, maybe? No, of course not. She uses the 4-year-old NEJM study demonstrating the efficacy of the then-new vaccine as the main basis of her claim, and it’s a house of cards from there. Let’s look at what she says, shall we?

First, let’s start with the 2007 NEJM paper. This paper tested the multivalent HPV vaccine, which contains HPV types 6 and 11 (these cause warts and aren’t further examined in this particular paper) and 16 and 18 (cause cancer, focus of this research). The goal was to “assess the prevention of cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, and cervical cancer caused by HPV-16 or HPV-18.” This makes sense that they’re looking at cancer outcomes only due to types 16 and 18–after all, while other HPV strains can cause cancer, HPV 16 and 18 are the only cancer-causing types included in the vaccine. They even note in the introduction that HPV 16 and 18 cause about 70% of all HPV-related cervical cancers, but that’s still not 100%. I mean, they state this right in the paper: “The primary hypothesis stated that, as compared with placebo, the vaccine would reduce the incidence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 in the per-protocol susceptible population.” I spell this out because this is one of Lenzer’s criticisms, which I’ll come to in a bit.

So they have this vaccine. Who did they test it on? In this trial, it was women ages 15-26, and the mean age of this group was approximately 20 years old. Age at sexual debut was 16–so on average, women in this trial had been having sex for about 4 years with 2 sexual partners by the time they were vaccinated. Now, for those of you familiar with the vaccine, that age range may seem a bit odd–because the vaccine is currently recommended to be given to girls starting at around age 11. But you see, this is one way they ended up at that recommendation–because of SCIENCE! (I’ll also come to that in a minute).

All right, they have young women, initially just a bit over 12,000 of them in 13 countries. Let’s look at their eligibility criteria (who could actually participate):

Women were eligible to participate in the study if they were not pregnant, did not report abnormal results on a Papanicolaou smear, and had had a lifetime number of no more than four sex partners.

That’s it, and it’s an important thing to note. For initial enrollment, they didn’t have to be HPV negative. This becomes important later.

The eligible women were randomized into the treatment or placebo groups, and then received 3 doses of the vaccine (or placebo), and were asked to report any serious adverse events for up to 15 days post-vaccination. The women also underwent pap smears and HPV testing at this point. They also had a number of follow-up visits to be re-tested, up to 4 years post-vaccination.

About those baseline tests. Even though they enrolled a bit over 12K women, they found that at baseline, pap smears were abnormal for 11.8% of subjects in the vaccine group and 11.1% in the placebo group. In other words, they were already infected with a strain of HPV at the beginning of the study. They further examined everyone using both DNA and serological testing for HPV 16 and 18, and found that about 10% of their cohort was already positive for HPV 16, and about 3-4% for HPV 18. Thus, they analyzed their data in several different ways, including doing an analysis including the pre-existing HPV 16 & 18 positive participants, and another one without them.

They also analyzed by eliminating participants who hadn’t fully followed or completed the protocol, including getting only one or two doses instead of the targeted three; having missing samples; or “general protocol violations,” which apparently consisted largely of not getting the month 7 swab at the right time, or administration of IgG, immunosuppressive drugs, or blood products–all things that could affect study outcomes.

Now the numbers. When they looked at women who’d followed protocol *and* were susceptible (ie not already infected with HPV 16 or 18 upon entry into the study), efficacy was 98% at preventing HPV-16/18-related high-grade cervical lesions. And what are “high-grade cervical lesions,” you might ask? According to the NCI:

High-grade means that there are more evident changes in the size and shape of the abnormal (precancerous) cells and that the cells look very different from normal cells. HSILs are more severe abnormalities that have a higher likelihood of progressing to cancer. HSILs include lesions with moderate or severe dysplasia or carcinoma in situ.

This is basically the step before cancer, and as noted above, one of the endpoints of the study, yet Lanzer calls them “innocent cellular abnormalities” and cites this paper, which doesn’t match her claim. If she’s referring to the line that “most HPV infections are easily cleared by the immune system,” I hate to break it to her that the ones that are “easily cleared” aren’t usually the ones causing the more serious dysplasia and carcinoma in situ. Rather, those HPV-caused lesions typically are examined via colposcopy and biopsy of the area to check for cancer. (Bonus scavenger hunt for the phrase “coffee ground-like discharge!”). Next, a woman with abnormal cells can expect to undergo a LEEP procedure, where portions of your cervix are removed with a burning electric wire under local anesthetic, and the foul smoking remains of your cells are sucked up into the smoke shark, “a sleep, powerful, smoke-eating machine.” After that one, side effects include infection, hemorrhage and possibly cervical incompetence. These are rare, but if we’re talking vaccine side effects versus possible outcomes from HPV infection, these types of outcomes need to be considered as well–not just death from cervical cancer.

What I’m trying to say here is that Lanzer may be minimizing these “innocent” non-cancer findings just a wee bit.

OK, so 98% efficacy in their target population who followed the study perfectly. What about if they included everyone? For that, they do what’s called an “intent to treat” analysis, basically putting everyone back in the pot. As Lanzer notes, this is when efficacy falls to a reported 44%, but she completely fails to note that the bulk of this was because the women had pre-existing HPV 16/18 infections and/or lesions. Like almost all vaccines, getting it isn’t going to help you if you’re already infected and showing symptoms. As I mentioned before, SCIENCE! This is why it’s so strongly recommended now to get the vaccine prior to the onset of sexual activity–if you’re already HPV-infected, the vaccine will not do you as much good. Hence, the current recommendation to receive the vaccine prior to the onset of sexual activity (ages 11-12ish).

OK, I’ve had about all I can take and this is getting to be a post of Oracian lengths. To jump to the end–why didn’t they just wait 20 years or so to see if there would be more cancers in the placebo versus unvaccinated group? Besides the whole waiting 20+ years thing, maybe because that would be totally unethical? I’ll take this right from the discussion section:

Although prevention of invasive cervical cancer is the main goal of prophylactic HPV vaccination, it is ethically unacceptable to use invasive cancer as the end point in efficacy trials. Cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ, which the International Federation of Obstetrics and Gynecology classifies as stage 0 noninvasive cervical cancers, are clinically important outcomes because they are likely to persist and may become invasive without treatment.

Thing is, even if they had followed these women for 20 years, doing checkups say every 6 months, they would have to follow standard treatment protocols (like the LEEP nastiness I mentioned above) and as such, would be doing everything they could to prevent cervical cancer in any case. So, these precancer endpoints are more ethical substitutes, and still show the ability of the vaccine to prevent abnormal cell changes that can lead to cancer.

Finally–Lenzer uses her supposed refutation of HPV vaccine efficacy in girls to then argue that we’re looking to give this vaccine to boys unnecessarily. She cites first that there are only 300 anal cancer deaths in the US every year (one of the cancers the HPV vaccine should reduce in men–and women, I might add). Small potatoes–why give the vaccine to boys over 300 deaths, right? But oddly enough (or, not?), she gives the barest of lip service to a group of HPV-associated cancers which affect men more than women, head and neck cancers. Guess what–there’s a lot more of those than anal cancers, and several studies suggest that HPV-associated head and neck cancers are actually increasing in incidence.

Even when she does mention oral cancers, she asks rhetorically, “what about the claim that Gardasil might prevent anal and oral cancers men may get from having sex with other men?” Um….why focus only on men having sex with men? Perhaps it hasn’t occurred to Lenzer that oral and anal cancers in men can also be transmitted to them by female partners, and vice versa–so we’re not just talking about “gay” cancers in men. I wonder if her wording was purposeful, though, as it’s easier for many in society to dismiss concerns about diseases that are transmitted via homosexual sex acts.

To wrap up, some drama. Lenzer frets about the possibility of developing Guillain-Barré syndrome from the HPV vaccine:

Given this, is it worth the risk of exposing millions of youth to the as yet uncertain harms of the vaccine? The CDC states that in rare instances, some vaccines may trigger the potentially fatal and paralyzing condition Guillain-Barré, and Nizar Souayah, MD, of the University of Medicine and Dentistry of New Jersey in Newark, says he and his colleagues found “clear evidence from our database of an increased incidence of Guillain-Barré syndrome in the first six weeks, especially the first two weeks, after [HPV] vaccination.” Guillain-Barré is very rare, even among people who are HPV vaccinated, but the problem is emblematic of the downsides of subjecting millions of people to any medical treatment.

The link takes you to a WebMD article from the 2009 American Academy of Neurology meeting reporting on a study by Nizar Souayah. The WebMD article states:

Overall, the vaccine does not raise the odds of developing Guillain-Barre syndrome (GBS), a disorder of the peripheral nervous system, says Nizar Souayah, MD, of the University of Medicine and Dentistry of New Jersey in Newark.

“But there is clear evidence from our database [the VAERS database–TS] of an increased incidence of Guillain-Barre syndrome (GBS) in the first six weeks, especially the first two weeks, after vaccination,” he tells WebMD.

Still, the risk is extremely low: 26 in 10 million in the first two weeks and 30 in 10 million in the first six weeks after vaccination. That compares to 5 in 10 million odds in the general population, Souayah says.

Leznar bills herself as an investigative reporter, but didn’t even bother to dig up the published version of this research. The numbers are fairly similar, so even if we accept that your chance of developing GBS from the HPV vaccine are 30 in 10 million (which are a bit sketchy coming from the VAERS database), that would still be only 3-6 times higher than those who didn’t receive the vaccine, with a condition that’s extremely rare to begin with. (To put it in perspective, the likelihood that you’d be struck by lightning in any year are about 1 in 750,000 according to NOAA). You have much better odds of contracting GBS from eating a poorly cooked chicken breast, as Campylobacter infections are a bigger cause of GBS than vaccinations. Even influenza infections cause more GBS than vaccines.

To sum up, in case it’s not painfully obvious by now, Leznar’s article is full of half-truths and omitted facts–so many that it would take me an entire series of articles to go through the rest of her post, and I haven’t even gotten into any post-2007 HPV vaccine research! To top it all off, she doesn’t even try the “fair and balanced” journalist approach, instead quoting only vaccine “skeptics” but not those who are in favor of HPV, and of then ends on the “I’m not anti-vaccine” note–she can’t be, as she thinks smallpox is bad! (Of course you’re not, neither is anti-vaccine advocate Barbara Loe Fisher. Is there a drinking game for that somewhere?)

I’ll end with my own addendum.

My 11-year old daughter is vaccinated for HPV. My 9-year-old son will be vaccinated. I wish they’d had the vaccine when I was younger, so I didn’t have first-hand knowledge of the Smoke Shark, who still haunts my dreams.

*And yes, I know that Discover is owned by the Gucciones, who have ties to another HIV denialist besides Duesberg and Margulis. [UPDATE: Turns out Guccione doesn’t appear to own Discover any longer, and that it was sold last year to Kalmbach publishing. Thanks to Ed & Razib for the correction.]

Comments

  1. #1 Nathan
    November 15, 2011

    I hadn’t read the Discover post, but this is a good critique of the common pseudoscientific arguments that I see time and again about HPV. Thanks. You have a great blog.

  2. #2 Leilah
    November 15, 2011

    Thanks so much for this – I saw her article and it puzzled the hell out of me. Without the background info, though, I couldn’t see what was going on. Much appreciated!

  3. #3 Orac
    November 15, 2011

    Jeanne Lenzer was co-author with Shannon Brownlee on a highly deceptive pseudoskeptical article in The Atlantic about the H1N1 vaccine back in 2009 at the height of the H1N1 worries:

    http://scienceblogs.com/insolence/2009/10/when_methodolatry_strikes_over_h1n1_influenza.php

    http://www.sciencebasedmedicine.org/index.php/yes-but-the-annotated-atlantic/

  4. #4 Orac
    November 15, 2011

    Oops. Last comment ended up in moderation, but I can’t resist adding that our very own revere demolished Lenzer and Brownlee’s article on H1N1 two years ago:

    http://scienceblogs.com/effectmeasure/2009/10/journalists_sink_in_the_atlant.php

    Lenzer strikes me as a bit of a hack who’s “skeptical” of vaccines; so seeing this sort of nonsense about HPV coming from her is not surprising. It’s a shame she’s on the same blog network as Ed, Carl, Razib, Phil, and Sean. Perhaps they should take it up with Discover’s editors, because if her history is any indication we can expect a lot more nonsense like this from Lenzer. What’s next? An article praising Barbara Loe Fisher?

  5. #5 Amos Zeeberg
    November 15, 2011

    Hi. I think some of these points are subjective, nearly philosophical questions–how closely should an experiment mirror real-world conditions; what ratio of risk/benefit should a treatment be shown to have before it’s widely adopted–that can’t be settled in a couple of blog posts. Some of the other claims are narrower and fact-based; Jeanne’s looking into them and will respond soon.

    -Amos Zeeberg
    Managing Editor, Online
    Discover

  6. #6 Tara C. Smith
    November 15, 2011

    Hi Amos,

    I disagree strongly that much of it is philosophical, but will wait to see the response.

  7. #7 JR Hoffman
    November 15, 2011

    Your smug, ad hominem and holiler-than-thou blog is full of all sorts of anti-scientific claims that should make an epidemiologist blush. While not everything in the Lenzer article was 100% accurate, its overall points are completely correct — this vaccine has NOT been shown to prevent actual CANCER (as opposed to cellular neoplasia) in any meaningful way, it has dramatically decreased value for the target HPV serotypes when given to females even as young as their teens (because so many already carry those serotypes), it has far less value for ALL cervical neoplasia (not limited to these serotypes — which ended up being substantial in the company’s own trials), and cervical cancer is not a disease of adolescent women (no less children).

    Cervical cancer is also a disease for which there are excellent public health approaches widely available (with which reliance on this vaccine might interfere). No — they don’t work perfectly, in the real world … which makes it ironic that you wish to discard all the real-world ways in which the vaccine also doesn’t work, and insist instead on looking only at the best possible results achieved in ideal patients under ideal conditions.

    You conveniently ignore all this by adopting a stance that violates the fundamental tenets of scientific reasoning, by ASSUMING, uncritically and without evidence, that vaccinating 7 year olds will solve any or all of these problems. (There are indeed many reasons to suspect this wouldn’t solve anything — but absent evidence, we can’t really know, one way or the other.) Yes, the vaccine MIGHT work well if given to young children — but it MIGHT not; it MIGHT also have to be given repeatedly, it MIGHT ended up causing substantial long-term advice effects, and these MIGHT be even far worse after repeated doses. There is no might, however, regarding the enormous costs (and profits) that would derive from its being given universally to little girls (and/ or boys) — and it is anything but scientific to suggest we shouldn’t wait for EVIDENCE of real benefit, and of absence of substantial harm, before employing it widely.

    There are many other issues about this vaccine that should raise further large questions and concerns, but I won’t address them here, since your post is so inappropriate, in both tone and content. I would ask one final question, however — what if any conflicts of interest might you have?

  8. #8 Ian Musgrave
    November 15, 2011

    Amos, Misrepresenting the study endpoints, misrepresenting the diseases that can be prevented and their seriousness, misrepresenting the relative frequency of side effects is NOT “philosophical” in the slightest.

  9. #9 Cath of Canberra
    November 15, 2011

    Smoke Shark???

  10. #10 Dan
    November 15, 2011

    Nice summary. I do some research in the area, specifically oral HPV and head and neck cancer, and have a few points to add.

    *Rates of anal cancer are very high especially among HIV+ Men who have sex with men (MSM) and recently evidence suggests anal HPV infection is much more common in MSM than men who have sex with women (MSW)(Nyitray JID 2011). However, this paper also suggests MSW also have anal HPV and it potentially suggests auto-inoculation as the source of transmission. Still, I hypothesize that the majority of anal cancers in men are likely among MSM, but not sure if we have enough data to back that up yet.

    *In terms of HPV+ oral cancers – I think it’s fair to say most of these cancers are likely among MSW. There’s also pretty strong evidence that the cancer is more commonly detected in males and increasing as you say (Chatervedi JCO 2011 provides the strongest evidence). The HPV+ oral cancer rate may actually be greater than cervical cancer soon.

    *There has not been any published data showing the vaccine protects against oral HPV infection and subsequently oral cancer. There is strong biological feasibility here, but I prefer to be cautious before having at least observational data showing protection.

    *There are clear evidence based benefits of vaccinating males – protecting against anal HPV (primarily benefiting future MSM), protection against genital warts (benefiting all males), and protecting females of cervical HPV via herd immunity.

    *The strongest case against vaccinating males is probably it’s lack of cost effectiveness. (See Kim JJ Annals of IM 2009) However I think it’s possible that vaccinating males may be cost effective given the low uptake in US girls (~33%) and if the vaccine protects against the recently increasing HPV+ oral cancer.

  11. #11 Mutant Dragon
    November 15, 2011

    Nice post! and yes, shame on Discover (AGAIN). Their post was misleading to say the least.

  12. #12 Matthew Cline
    November 15, 2011

    and of then ends on the “I’m not anti-vaccine” note–she can’t be, as she thinks smallpox is bad

    All it takes to be non-anti-vaccine is to think that smallpox is bad?

  13. #13 Henry Linneweh
    November 15, 2011

    Will it kill genotype1 virus, permanently? Or just remiss for a while?

  14. #14 Tara C. Smith
    November 16, 2011

    Jerome, I find it hilarious that the first thing you accuse me of is ad hominem attacks, and then end your post with attacks on my credibility via accusations of conflict of interest. I have zero pharmaceutical funding. The only industry funding I’ve ever received is from the National Pork Board, and this isn’t exactly their area of concern. My research funding comes from AHRQ, NIOSH and USDA, none of which is in any way related to cancer or any pharmaceutical drugs beyond antibiotics (and my research suggests controlling use of them, not exactly winning me drug industry friends). All of this is easily searchable if you’re so very interested and not just seeking to make rhetorical points.

    You also make accusations not in evidence. I’ve never suggested an either/or approach for cancer control. I think the vaccine should be yet another tool in the arsenal. Certainly you realize how many women already lack access to primary preventative care in the US, and as a global health issue, that issue is magnified a thousand-fold. Indeed, screenings are great, treatment often works well, but as I note in the post, even those are not without their own pain and side effects.

    I’m also not in any way arguing against real world issues. I’m merely pointing out that many of these have been taken into account via the target group for the vaccine–the biggest issue was prevalent HPV infections at entry into the study, something that should be low to non-existent in 11-12 year old girls. (Where you got the age of 7, I’m unclear as I never said that). Getting all required doses may certainly be an issue, but at least for the bivalent vaccine, it seems that even a single dose may be effective–so perhaps that won’t be as much of a problem as thought. (Remember that many of your unknowns can work both ways).

    I’m curious–what would you suggest as far as waiting for “EVIDENCE of real benefit, and of absence of substantial harm, before employing it widely.” Millions of girls have now been vaccinated with minimal side effects. The worst Jenzen could come up with was a slightly elevated risk of GBS, which was still incredibly rare, so absence of substantial harm seems to be already in evidence. Yes, true cancer outcomes remain to be seen, but I really don’t understand why reduction in pre-cancerous lesions and neoplasia themselves aren’t also an important endpoint. Certainly you must know how much procedures like biopsies and LEEP cost, both in terms of actual dollars spent as well as in time off work, anxiety/mental health issues, and recuperation/pain. We already know that HPV vaccines prevent these from several clinical trials–why aren’t these outcomes valued? With every other vaccine-preventable disease, we look at reduction in both morbidity and mortality–why is HPV being treated so much differently than, say, chickenpox, pneumo or Hib?

  15. #15 Kavinace
    November 16, 2011

    The Food and Drug Administration has approved one HPV vaccine and indications are that a second vaccine will be approved in the near future. HPV is a sexually transmitted virus which is known to cause multiple types of cancer and other diseases.

    Kavinace Ostaderm

  16. #16 Joshua Nicholson
    November 16, 2011

    “Lenzer strikes me as a bit of a hack who’s “skeptical” of vaccines; so seeing this sort of nonsense about HPV coming from her is not surprising. It’s a shame she’s on the same blog network as Ed, Carl, Razib, Phil, and Sean. Perhaps they should take it up with Discover’s editors, because if her history is any indication we can expect a lot more nonsense like this from Lenzer. What’s next? An article praising Barbara Loe Fisher”?

    Dear “Orac,”
    First, why do you hid behind an anonymous name? Second, why do you do so and suggest censorship of another writer because you disagree with them?

  17. #17 Orac
    November 16, 2011

    Point one: I am hardly “anonymous” anymore, although I do still use a nom de blog on ScienceBlogs. In fact, one of the links I included contains a strong hint to my identity (no, I”m not Mark Crislip, although it would be cool if I were), and my real identity is one of the worst kept secrets in the blogosphere. It’s not my fault if you don’t know it, nor do I feel obligated to help you along. Indeed, complaints about my supposedly being “anonymous” amuse me, given how many times cranks have found my real identity and tried to harass me. (My post on my own blog today even mentions how last year an anti-vaccine crank tried to get me fired from my academic job.)

    Point two: No one is suggesting “censorship.” I merely suggested that the bloggers whose work I respect should keep an eye out for more shoddy blog posts and act accordingly (as in complaining to their editor, given that their complaints would probably have more heft than complaints from random readers). No one has an intrinsic right to write for a large blog network or a magazine, and if they promote distorted information said blog network or magazine has every right (nay, duty) to enforce editorial standards.

    Point three: One can’t help but note that you have not refuted a single one of Tara’s points about Lenzer’s most recent post or any of the points made about her Atlantic article two years ago by Mark Crislip, revere, or myself. Instead, you complain about “anonymity,” which is basically an ad hominem, rather than a a substantive, argument.

  18. #18 Joshua Nicholson
    November 16, 2011

    Dear “Orac”,

    “This is basically the step before cancer, and as noted above, one of the endpoints of the study, yet Lanzer (sic) calls them “innocent cellular abnormalities” and cites this paper, which doesn’t match her claim.”

    This is not basically the step before cancer. And Lenzer is correct in that they are largely “innocent cellular abnormalities” Only 5% of the time do they progress to bona fide cancer.1

    1.
    Andrew G. Ostor, International Journal of Gynecological Pathology 12, 186 (1993).

  19. #19 hadron
    November 16, 2011

    *grabs popcorn*

  20. #20 Tara C. Smith
    November 16, 2011

    I don’t have access to that paper, but progression to cancer depends on many variables, including treatment/removal of the pre-cancerous lesion. I don’t know if that was included in your paper’s 5% figure or not. Here in the US we do have routine screening which means we have less actual “bona fide” cervical cancer diagnosed; as I mentioned above, this is not so globally. According to the American Society for Colposcopy and Cervical Pathology, “HSIL lesions have significant malignant potential. It is estimated that 30 to 50% of HSIL lesions will progress to invasive disease if left untreated.” I will note that saying it’s the step before cancer doesn’t mean that *every* lesion will progress to cancer–again, many are treated, some will remain at the pre-cancer stage indefinitely, some will regress, and some will progress to cancer. This really isn’t controversial.

    I do again disagree strongly with the “innocent” comment. This description is incredibly minimizing to every woman who’s ever had to deal with treatment/removal of a lesion, which as I described in the post, is no laughing matter. I wonder how much more men would support a vaccine like this if they had to get treated for a vaccine-preventable infection by burning off a piece of their penis or scrotum, which happens to the cervix as treatment for what Lezner calls an “innocent cellular abnormality.”

  21. #21 Tara C. Smith
    November 16, 2011

    This is also a nice overview of screening and cervical cancer.

  22. #22 jre
    November 16, 2011

    It depends on the atypicality. Here’s the abstract for Ostor (1993):

    The literature dealing with the natural history of cervical intraepithelial neoplasia (CIN) since 1950 is reviewed, in particular from the viewpoint of regression, persistence, and progression. When stratified into the various grades of severity, the composite data indicate the approximate likelihood of regression of CIN 1 is 60%, persistence 30%, progression to CIN 3 10%, and progression to invasion 1%. The corresponding approximations for CIN 2 are 40%, 40%, 20%, and 5%, respectively. The likelihood of CIN 3 regressing is 33% and progressing to invasion greater than 12%. It is obvious from the above figures that the probability of an atypical epithelium becoming invasive increases with the severity of the atypia, but does not occur in every case. Even the higher degrees of atypia may regress in a significant proportion of cases. As morphology by itself does not predict which lesion will progress or regress, future efforts should seek factors other than morphological to determine the prognosis in individual patients.

    So, contra Joshua Nicholson, abnormalities in the CIN 2 and 3 categories (clinical endpoints of the HPV vaccine Phase 3 trials) progress to invasive cancer at a rate quite a bit higher than 5%, since CIN 3 progresses to cancer 12% of the time, and CIN 2 progresses to CIN 3 20% of the time. “[I]nnocent cellular abnormalities”, my ass.

  23. #23 Mike Olson
    November 16, 2011

    Holy Cats!

  24. #24 Matthew Cline
    November 16, 2011

    Yeah, something which has a 1 in 20 chance of becoming cancer doesn’t seem “innocent” to me.

  25. #25 Anna-Lise Williamson
    November 20, 2011

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1840339/?page=5
    This article describes a trial in New Zealand where doctors tried to prove that premalignant cervical lesions did not progress to cancer. Some women died because they did not get treated.

  26. #26 dt
    November 21, 2011

    Wow! That NZ info is a real eye-opener.
    I just hope all these antivax people and the promoters of ideas like “HPV is “innocent” it will all just disappear” get a look at it.

  27. #27 dt
    November 21, 2011
  28. #28 Amos Zeeberg
    November 23, 2011

    Hi. Jeanne’s response is up. http://blogs.discovermagazine.com/crux/2011/11/23/how-effective-is-the-hpv-vaccine-at-preventing-cancer-a-closer-look/

    I think it presents an accurate, forceful, detailed argument for questioning how much we know about the real-world effectiveness of the HPV vaccine. Note that I’m not saying Discover officially agrees with her on this–we’re presenting her piece in our blog because it represents a legitimate viewpoint based on solid evidence and rational analysis, and is backed by many experts. While this is her personal take, it’s a scientifically solid and interesting one, so we’re happy to help get it out.

    I also want to respond to your implication that Lenzer tried to minimize oral and anal cancer by framing it as a gay disease. (I’ll keep this short; arguing about arguing is pretty tiresome.) Her wording may have been imprecise there (see the new post for clarification), but there’s little justification for imagining such a nefarious intent on her part. You shouldn’t profess to read what’s going on in other people’s minds, especially when it’s to accuse them of playing on society’s homophobia.

  29. #29 Wzrd1
    November 23, 2011

    Amos, JR, you’re absolutely right on all counts!
    BRING BACK SMALLPOX!!!!!!!!
    Vaccinating 7 year old children never eliminated disease, smallpox died out naturally, right?
    To use Amos’ filter, smallpox SHOULD be re-introduced, as the studies aren’t up to snuff to his lunatic standard.
    Come to think of it, using Amos’ standard is WHY polio still plagues the world.
    So, with no due respect, sirrah, I’ll file your opinion with my used toilet paper and flush it.
    Right along with JR’s opinion.
    For, what counts is what is proved: VACCINATION WORKS, *NOT* vaccinating spreads disease and regardless of WHICH witchdoctor you consult, the disease continues to spread.
    Of course, I’m relying on the unscientific method of proved results and the science that backed THEM.
    Indeed, as the smallpox vaccine had an alarmingly high rate of progressive vaccinia, we should re-introduce the disease and ban the vaccine until 20 years of testing proves the vaccine, by the standards of idiots like yourselves.
    As I’m as for re-introducing an extinct in the wild disease (unless you wish to claim that smallpox is still extant) as I’d be for playing Russian roulette with artillery, no disease will be re-introduced and no vaccine against said disease will be banned. Unlike you, I am sane and have some degree of intelligence.
    And experience has taught me long ago to trust the epidemiologists, THEIR data sets are far more reliable than the data sets of folks like you.
    But, I AM blocking all traffic now for Discovery’s networks at my network connections.
    I’ll miss Bad Astronomer!
    But, quarantine has proved effective in preventing the spread of many diseases, including idiotic notions.

  30. #30 Wzrd1
    November 23, 2011

    Full disclosure, I’m extremely prejudiced against antivax lunacy due to SF duties in remote areas where antivax sentiments were high, as was the polio rate.
    My favorite aunt also died from cervical cancer.
    And the block on Discovery networks will remain. We’ll determine on a case by case basis if our clients networks will permit the traffic, but as it’s not business related, it’s highly likely that the block will spread.
    Because, as the Taliban noticed, I’m also very, very, very vindictive against those who attempt to cause harm to innocent people.
    But, I’m being far, far, far, far nicer here than what was done over there.

  31. #32 dt
    November 24, 2011

    @Amos Zeeberg, who said about Jeannes latest comment:

    While this is her personal take, it’s a scientifically solid and interesting one, so we’re happy to help get it out.

    Jeanne has tackled none of the science, and her response is hardly scientifically “solid”. It consists of sleight of hand evasions of the issue of vaccine efficacy, cherry-picked quotes to support her confirmation bias, and multiple strawmen. Read the responses.

  32. #33 Wzrd1
    November 25, 2011

    Small update. ALL traffic from Discover’s networks has been successfully blocked at our network borders, save for Phil Plait’s blog. That has the ONLY traffic permitted to our networks.
    NEVER PO someone who naturally THINKS in regex!

  33. #34 DaveC
    November 26, 2011

    Link surfing related to this lead to Marketing HPV Vaccine, 2009 JAMA. (Couldn’t get to any of the full text). I accept your conclusion the clinical effectiveness of the HPV vaccine, but I think the post would be stronger with some concession to the some of the real world public health issues of cervical cancer, particularly the tension between aggressive vaccine marketing and established pre-vaccine public health approaches. Merk funding Gardasil promotional/ educational campaigns doesn’t make the vaccine ineffective, but it makes me leery. I’ll bet somewhere along the way you tell your vaccinated daughter she should still be getting pap smears even if she has already been vaccinated, seems like that would fit in your personal note.

    Being a guy, I am more interested in the effectiveness of the vaccine in men. My impression from more link surfing is that the public health severity of HPV infection in men isn’t going to be enough to justify investment in trials by big pharma. That weakens the argument for vaccinating men and boys. It would be particularly sad if men rationalize promiscuity (bestiality?) based on HPV vaccination. I could have missed it, but I didn’t see any reports of HPV vaccination trials with men. (So on that personal note, you or some appropriate authority figure should really have a meaningful conversation with your son about HPV, his sexuality, and the vaccine).

    Sorry to be late to the party, great read.

  34. #35 Tara C. Smith
    November 27, 2011

    Catching up–had family issues over the holiday and heavy class load until Wednesday, but will read the new post and respond likely late this week.

  35. #36 Nathan
    November 29, 2011

    DaveC, I’m surprised you haven’t come across HPV vaccine studies in males. Here is one in the NEJM earlier this year that I had bookmarked.

    http://www.nejm.org/doi/full/10.1056/NEJMoa0909537

  36. #37 Nathan
    November 29, 2011
  37. #38 Rokujolady
    December 22, 2011

    Only tangentially related…I had to go read the Duesberg article. Yeah it’s a bit shockingly forgiving even to someone who knows nothing about the history of AIDS denial. If you’ll excuse a little evidence-free fantasy, he seems like he is so ashamed of his parents that he’s decided it’s his duty to be the lone wolf against the establishment, even if the establishment killed, buried, and built a parking lot on top of his alternate theory years ago. In doing so, he has become morally reprehensible,callous and egotistical.
    That being said, I’m perfectly willing to believe that good ideas can and do sometimes come from unexpected places and that the politics of academia and the emphasis placed on scholarly reputation could result in those ideas being lost.

  38. #39 medschneverends
    February 5, 2012

    Hey.

    Just for comparisons sake, does any one have information about clinical trials for men that is not funded by Merck?

  39. #40 cal crilly
    March 14, 2012

    HPV is endogenous and caused by hypomethylation just like all the other viruses.
    This is why folate is the biggest factor in both HPV emerging in keratin tissue and the emergence of cervical cancer.
    The correlation works with brain tumours and herpes infections too.
    Viruses are transmitted from one genome to another but they are still endogenous and caused by chromatin and histone instability.
    The other big factors in cervical cancer are sexual lubricants, the pill, HRT and just plain simple things like candida which cause hypomethylation.
    HPV vaccine is very simplistic propaganda to sell a useless product.

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