Questions on the Cervical Cancer Vaccine - Updated

Howdy, folks. My name is Mrs. Peel, and Ace invited me to guest-blog this weekend (which doesn't make him responsible for anything I write, incidentally). I'd like to take advantage of the opportunity to reach a larger audience to discuss the new "cervical cancer vaccine" that has just been approved by the FDA.

First of all, to explain my scare quotation marks, the vaccine is actually against four strains of human papillomavirus (HPV). Not all cases of cervical cancer are caused by HPV. According to Science Daily, the four strains against which this vaccine protects include the two that cause roughly 70% of all cases of cervical cancer. All four strains cause about 90% of cases of genital warts. So, referring to this vaccine as a "cervical cancer vaccine" isn't entirely accurate, and is somewhat misleading, as it implies that the vaccine completely prevents cervical cancer in the same way that the mumps vaccine completely prevents mumps.

By the way, I'm not suggesting that Merck is deliberately attempting to mislead the public. Merck is not responsible for the phrasing reporters and editors choose.

I've found that the news articles on the vaccine are somewhat lacking in scientific depth, so I've been checking the science news for more information. In the New Scientist article, I ran across something I hadn't noticed before:

Four different clinical trials involving 21,000 women around the world demonstrated Gardasil was "nearly 100% effective" in preventing HPV-caused precancerous cervical, vaginal and vulvar lesions. It also prevented genital warts effectively, the FDA said.

"While the study period was not long enough for cervical cancer to develop, the prevention of these cervical precancerous lesions is believed highly likely to result in the prevention of those cancers," the FDA said. [Emphasis added.]

This was a fast-track clinical trial that lasted six months, according to that same article. Merck, as I've read in several articles, is going to continue to perform follow-up testing and study the long-term effectiveness of the vaccine, including evaluating the need for booster shots. They will also be testing the vaccine in men.

I have a number of questions, most of which were answered in Merck's prescribing information, and some of which will be answered by the long-term studies. But some remain unanswered.

Update: Craig answered these in the comments, so I'm putting his answers here, in italics. Thanks, Craig!

1. As the FDA acknowledged above, the study wasn't long enough for cervical cancer to have developed. On what is the belief that prevention of precancerous lesions equals prevention of cancer based?
   The reason we know that precancerous lesions lead to cervical cancer is through many studies that have followed these cells. The proof is in the pudding of pap smears preventing cancer by detecting these early lesions. Carcinoma type cancers usually evolve from an abnormal cells in the single cell lining of the cervix that multiplies, then it can become a carcinoma in situ or CIS, a precancerous lesion. When it moves into the cervical tissue, below the single cell lining it is then a cancer. It can get access to other systems and spread.
2. Considering that thalidomide, for example, is teratogenic in humans and in rabbits but not in rats, why was teratogenicity studied only in rats?
   The chances of the proteins used in vaccinces causing mutations like thalidomide, are very low since they are protein based and not small chemicals.
3. The patient populations are large enough (roughly 8500 in each group, drug and placebo) to suggest that we can assume similar levels of sexual activity in each group, and therefore similar levels of HPV exposure. However, I would like to see the statistical analysis that validates these assumptions.
   Yes, it would be nice to have the measured sexual activity, but it is pretty safe in this large sample to assume the groups are similar.
4. Reading the study, I see that the populations were tested for the relevant strains of HPV via PCR and serum testing prior to vaccination, and through the series of shots (there are three, costing $120 apiece) up to one month after receiving the last shot. There's no reference to further PCR and serum testing being performed thereafter - just examinations for warts and lesions. Considering that HPV can remain dormant in the human body, with what statistical certainty does the lack of warts and lesions over the duration of the study signify a lack of HPV?
   PCR after the vaccine would show that a virus got into the system, which may still be possible after having the vaccine. As someone else pointed out the virus may be knocked down better with the vaccine and not eliminated. Serum tests would probably be for antibodies, which the vaccine would result in, so they wouldn't mean much about infection.

I should clarify that I'm not a medical professional or a statistician, and the decision to be vaccinated or have your children vaccinated should be based on your discussion with your doctor. But as a woman in the target age group, I'd want these questions answered before I got vaccinated.

posted by Mrs Peel at 02:40 PM

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