Over and over I see people concerned about the long term implications of only vaccinating against High-Risk HPV types:
If we vaccinate against types 16 and 18, wont other HPV viruses evolve to fill that empty niche? Wont other HPV step up to cause cancer?
This is a valid concern. With viruses, you need to get rid of it all, or you get rid of nothing. Say we figure out a perfect vaccine for HIV-1 Subtype C. We get rid of all HIV-1 Subtype C on this planet. Other subypes of HIV-1 will step up to fill that void... and youre back to where you started. Ugh.
But the answer to the question about HPV and cancer, specifically, is: NOOOO.
And by that, I mean: NOOOOOOOO.
One thing that I dont even think other biologists appreciate is that especially with viruses, sometimes, 'shit just happens'. Sometimes viruses do shit that has no adaptive value. Just do to their randomness and HUGE numbers, shit just happens.
There is no evolutionary benefit to HPV causing cervical cancer. None. Technically, its a negative, as transformed cells produce no virus.
Its an accident.
Its a mistake.
There is no adaptive advantage to an HPV that causes cancer.
It could be that 'any' HPV can cause cancer, by accident, its just that HPV 16 and 18 are the most prevalent HPVs, so they get the most 'chances' to make a mistake.
But thats not the case. 16 and 18 cause a teeny-tiny minority of all HPV infections.
Getting rid of them is not going to create an ecological vacuum that will necessarily be filled. While 'shit might happen' again, there is no evolutionary 'reason' to fill the 'HPV cancer' void.
Get your vax against HPV 16 and 18. Obliterate those assholes from the planet.
(Washington, D.C.)-- The White House today announced noted virologist and D-list blogger Abbie Smith as directory of the National Institutes of Health. Smith was named the replacement for religiobot and all-around fuddy-duddy Francis Collins after Smith "womped him good" in an arm-wrestling match, according to unnamed sources.
Smith, a reality-based human, has long been an advocate of doing the right thing when it comes to vaccines and general health issues, and has a noted disdain for creationists, religious intolerance, and those who deny live-saving solutions for women. She also has a "Puppy!" named Arnie.
Hey! Abbie, you just said that HPV 16 and 18 were making mistakes. And then you call them assholes? That's not nice! If we've just established they aren't doing it deliberately. You are mean scientist!
This is actually something I was wondering about though. Thanks for educating us. Even if you are a meany to the poor defenseless viruses.
Get your vax against HPV 16 and 18. Obliterate those assholes from the planet.
Abby, that's a damned unfortunate phrasing. HPV 16 and 18 also infect the anus and cause anal cancer -- with, frankly, rather more impact on the lives of most victims than cervical cancer does.
Stephanie isn't looking forward to the removal of a big chunk of her cervix, but doesn't have much in the way of other plans for it. Her anus? Different story.
Also, more serious and sobering, Stephanie has an update on her status http://almostdiamonds.blogspot.com/2009/10/good-news-but-complicated.ht… .
Do you know/care enough to do a post on what differentiates the different strains of HPV and why it's only been possible to hit 16 and 18 so far?
It's not ONLY been possible to hit 16 and 18. Infact gardasil covers 6, 11, 16, and 18. It's that 6 and 11 are very prevalent (i think 90% of genital warts), and 16 and 18 cause the most cervical cancer (i think 70%)
Hmmm..Wait. Cancer cells produce no virus..you mean cancer is immune to viral infections? All cases? what's the 2-bit explanation?
I hadn't given any thought to warts. But presumably it would still be desirable to hit more strains, particularly since there isn't any chance of benign strains outcompeting malignant ones, if I understand Abbie correctly.
So I'd like to know what it is in the vaccine that the immunesystem hits, and why we haven't been able to 'catch' that bit on the remaining strains.
I am not sure I understand your reasoning for why selective pressure from the vaccine may not have an impact on the freqeuncy of non-16, non-18 HPV infection. Given that a substantial number of other high risk strains of HPV already exist(currently causing ~30% of cervical cancers) it is conceivable that the incidence of dyplasia caused by these strains could increase in number (even while the absolute incidence of dyplasia/cervical cancer goes down since 70% of cases were HPV 16 or 18 related). This is especially true if there were co-incident changes in behavior in the population that favored transmission.
An analogy from the bacterial world would be the increasing emergence of cases bacterial infection caused by Serotype 19A Pneumococcus (not covered by the current Prevnar-7) even while the vaccine has been effective in reducing overall disease.
While not necessarily a reason to forgo immunization, I am not sure that we have a good handle on what changes in HPV strain distribution and frequency will arise from the deployment of the vaccine.
Short answer is that the Gardasil vaccine is comprised of the primary capsid protein from each of the four target HPV strains which assemble into virus like particles.
While there may prove to be technical issues associated with the development of analgous vaccines for the ~15 other high risk HPV strains in circulation, the primary reason that there is not broader coverage in the current vaccine is the difficulty in developing, testing, and manufacturing such a complex vaccine (especially when the basic safety and efficacy of even a narrowly focused vaccine had yet to be established).
ERV: Good one.
Well said. Cancers caused by viruses are biological accidents just as cancers that do not have an infectious cause are biological accidents. Getting rid of these two assholes would be just fine for everyone.
Abbie, you rock.
D. C., I think that actually makes the wording choice more apt. And we shouldn't forget that HPV may also be implicated in cancers of the penis, mouth and throat as well.
Take a look at the question ERV quoted again. It specifically relates to the causation of Cancer by HPVs - "Won't other HPVs step up to cause cancer?"
The majority of other HPVs do not cause Cancers, and types 16 and 18 are a minority of cases. They have a maladaptation that causes Cancers in infected patients that also reduces the reproductive potential of the virus as the cancerous cells do not produce any viral bodies. This trait, therefore, is significantly less likely to re-emerge than a positively selected trait.
Eliminating these strains will reduce the incidence of this dangerous affliction (the Cancers, that is) in both the short and long term.
I am not a Biologist, but I believe that cancerous cells caused by these strains occur because of faulty genome injection, negating the potential to hijack cellular functions to reproduce the virus.
It is funny to read about faith in current scientific explanations. Thanks.
Thanks Pseudonymous. I'm thinkin I have to get my hands on a good book on viruses.
Hey, Willy's back, smugly pitying us for our faith that the earth isn't flat and disease isn't caused by demons.
Keep in mind that Wallaids is also an anti-vax nutcase.
I am not sure what you mean by "faulty genome injection", but HPV is not a retrovirus. It is maintained episomally in the cell. Although all the process of cancer development is not completely understood, key contributors include the expression of the oncogenic viral proteins E5, E6, and E7 in the cell. E5 leads to disruption in several cell signalling pathways and may also favor avoidance of the immune system through MHC downregulation. E6 and E7 inactivate endogenous tumor suppresors. All of these are favorable for viral replication at least prior to transformation of the epithelial cells (I cannot comment regarding the erv's assertion that the viruses no longer replicate in transformed cells).
I appreciate your comment to me to help clarify the original post, but I am afraid that I still do not understand erv's response to the "Won't other HPVs step up to cause cancer?" question, specifically, because there are already 15 other HPV subtypes that do cause cancer. We are fortunate that none of these are as widespread and/or oncogenic as 16 and 18, but that is not necessarily a static condition.
With regards to the argument that selective pressures will be biased against cancer causing strains I would like to hear more. It is my understanding that the most important factor contributing to cancer development is the ability of the virus to avoid detection and clearance by the immune system (i.e., chronically infect the host). This seems like a useful adaptation for the virus even if it has deleterious consequences in the very long term.
Your post ignores that there are already a whole basket of non-16/18 oncogenic strains circulating in the population.
A virus doesn't have to suddenly start causing cancer to be of concern, it could just get better at what its supposed to be good at - circulating in the population.
There is an excellent and concise letter in the NEJM regarding this topic.
As an aside, what is the proper internet etiquette for posting a link to a journal article?