Tuesday, January 29, 2008

The Virus/Cancer Connection (Part 4): Vaccines, Cervical Cancer, and a Recap

Everyone is familiar with the idea that getting vaccinated can keep viruses away. Every year millions of people get the flu shot for just that purpose. If viruses can cause cancer, can vaccines be used to prevent cancer? Of course they can! The best example of this is a pair of new vaccines called Gardasil and Cervarix which prevent cervical cancer.

Cervical cancer? The cancer women get Pap Smears to detect?

Yes, cervical cancer. It turns out that cervical cancer is caused by a virus called human papilloma virus, or HPV. There are more than 100 different strains of HPV, and at least 30 of them are transmitted through sexual intercourse. HPV infection is common, and by age 50 at least 80% of women will have acquired a genital HPV infection.

If 80% of women develop an HPV infection, why don’t 80% of women get cervical cancer? Most of these infections are cleared by the woman’s immune system with no long term consequences. Fortunately, only a small fraction of HPV strains are capable of causing cancer, and these only in the case of a persistent infection. So once again, it appears that a viral cause of cancer requires more than just exposure to the virus. For cancer to develop, it requires a complex interaction between the virus and the patient’s immune system.

Where do the vaccines fit in?

The vaccines cause the body to develop antibodies against 4 of the most common strains of HPV that are associated with persistent infection and with the development of genital warts and cervical cancer. These antibodies help the patient clear the viral infection before it becomes persistent, and thus prevent the development of cancer.

Why is this controversial?

Well, these vaccines are preventive, rather than therapeutic. So they have to be given before exposure to the virus. If the virus is spread through sexual intercourse, that means prior to the initiation of sexual activity. The Advisory Committee on Immunization Practices recommends the vaccine for girls as young as 11, and some school districts have begun to require HPV vaccination just as they require vaccination against chicken pox and whooping cough. One possibly troublesome issue about requiring an HPV vaccination is that some parents may have an issue with vaccinating their little girls against a sexually transmitted infection.

What about men?

Don’t sexually transmitted infections go both ways? Certainly they do. But because cervical cancer is a disease limited to women, all of the clinical testing was done on women, so the vaccines are currently only approved for women (and girls). Clinical trials are ongoing in men, but because they are not completed, there are no data regarding the safety or efficacy of the vaccine for men and no data about whether vaccinating men impacts the rate of cervical cancer in their partners. Also, HPV has been associated with penile and anal cancers in men, so there may be a direct benefit to vaccinating men, but this has not yet been studied either.

Recap: So what have we learned?

Although we don’t usually think about it this way, cancer can be caused by a viral infection. Many cancer-associated viruses, like EBV, are very common, and yet they rarely cause cancer. This is because the interaction between the virus and the patient is quite complex, and only in very rare circumstances does EBV (or HPV, for that matter) cause cancer. However, the fact that viruses can cause cancer teaches us a lot about the role of the immune system in controlling cancer, the impact of the environment on cancer risk, and a host of other lessons that are important in thinking about all forms of cancer.


kab625 said...

Hi Doctor David,

That's a great article. Too many people feel that vaccines are dangerous. The public may be minimizing past successes with polio, pertussis, cholera, rabies and tetanus due to concerns about vaccine safety - propagated by news media and the Internet. Many parents insist on natural immunity for diseases such as measles.
The CDC reported that between 1989 and 1991 there were 55000 measles cases due to underimmunization. Do we really want these diseases to re-emerge?
Parents need to consider the dangers of natural immunization.
In the case of HPV natural immunity is an impossibility.
HPV vaccine is 95 - 100% effective. Studies show that the rate of HPV in college age males is high so it's important to get the vaccine early. Thanks for the great information.
HPV vaccine not only prevents cervical cancer, but it's effective against vulva and vaginal cancers as well as genital warts.
I think it's important that you are lending your support and expertise to such a vital issue.

Doctor David said...

I'm glad you raised the issue of HPV infection in college age males... keep watching this space for a discussion of HPV infection (and vaccination) in men... coming soon!

Emily said...

Gardasil was developed at the medical school I attend. I have a couple of comments:

1) Cervarix is a politically motivated vaccine. While Gardasil protects against the 2 most common HPV strains that cause cervical cancer in america (HPV 16 and 18 cause 70% of cases), it also has vaccine against the two strains that cause the majority of genital warts (6 and 11). Cervarix only has the two HPV strains that cause cervical cancer, and the two that cause warts are not included so that the vaccine can more easily be marketed to conservatives who don't want to vaccinate their kids against an STD. This in some ways is positive (kids who may not have been vaccinated may have a chance now), however, it also means that even though they could be protected against warts, they won't be.

2) In america, this vaccine is really not needed (although it's great we have it). Women have access to pap smears, and the vast majority of women have precancerous lesions detected. The pap smear has dramatically reduced the risk of developing cervical cancer, and the number of women who die from cervical cancer is extremely low compared to before the pap smear. However, in developing countries where there is no access to paps (you need a clinic, someone to perform them, a lab to interpret them, and then a way to contact the patient when you get the results), cervical cancer is the number one cancer killer of women. These women need access to this vaccine. But even more so, they need a better vaccine. Gardasil prevents against the two most common HPV strains in the US, not the most common ones worldwide. We need to develop a better vaccine that has the right strains, and we need to be able to effectively distribute it in a cost effective way.

3) HPV causes anal cancer by the same mechanism as it does cervical cancer, and for all intents and purposes, the pathophysiology of the disease is the same (it occurs in the transitional zone, etc). Men who have sex with men are at a very steep increased risk for developing anal cancer, just as women are at a risk of developing cervical cancer. The HPV vaccine should be very effective in this population, and there is no indication that it will work any differently than it does in women (of course, the original trial was conducted only on women, hence the approval only for women). However, there are a number doctors giving the vaccine to this population of men off label. Eventually it will be approved for all men - but this particular population is especially vulnerable, and they should be encouraged to get the vaccine off label, and more doctors should be vaccinating them.

Doctor David said...


Thank you for your excellent comments. I agree with you wholeheartedly. My next post on this topic (in preparation) was actually going to be about HPV in men and why boys should also be vaccinated. You stole my thunder, but I'm going to post it anyway.

Mindy said...

Doctor David, I have enjoyed reading your blog, but have a question that is not clear. I know you have stated your opinion on Guardisil and the like, but is there anything wrong with trying natural treatments for the warts themselves first? I saw that some were recommended by the community at http://picturesofgenitalwarts.org/category/community/ but from what you are saying that doesn;t do anything for what's inside the body correct?

Thanks for your help!

Doctor David said...

Hi Mindy,

Great question! Most treatments for genital warts treat the skin overgrowth itself, but not necessarily the virus. But there is nothing wrong with trying them first, since sometimes warts that are removed by whatever means just don't grow back. But it is important to understand that unless you get rid of the virus itself, there is still a risk for new warts and for cervical cancer.

Also, Gardisil is for the prevention of HPV infection, not treatment.