Sunday, February 04, 2007

Questioning Gardasil

Maia at Alas, A Blog, as well as brownfemipower at Woman of Color Blog, are voicing some concerns about the idea of requiring the new HPV vaccine Gardasil for entry into public school, and as someone with a little training and knowledge in biology and public health, I thought I might weigh in with a few ideas.

Consider this from Maia's post:
As I understand it the only way a vaccine can be available to all, and publicly funded in America is if it is compulsory before a child can attend school (there are exemptions available to parents for conscience reasons). I can understand the public health argument which says that a kid must be immunised from certain infectious diseases before they start school (I don’t necessarily agree with it, but I understand it), disease can travel very quickly among unorganised children at school and this can cause an epidemic. But this logic does not apply to the HPV vaccine, HPV is a lot harder to contract than measles, so it isn’t going to spread round a school in the same way (it is clear that the vaccine is as important for later in life as it is for 6th grade, unlike other vaccines) and any genuine worry about the disease spreading would require both boys and girls to be immunised. There appears to be two reasons to support compulsory vaccination, either because your in the pay of the drug company, or you believe that it’s important that poor women get access to the vaccine (or both). Neither of these are based on genuine health concerns.
There are a couple of reasons to vaccinate children against HPV before they enter school. It's a good way to reach most children, and as they're entering school, they're young enough and have been isolated enough that it's not likely they've been exposed to the diseases they're going to be immunized against. Maia's right that going to school isn't what exposes a kid to HPV, but most kids go to junior high, and most kids haven't been exposed to HPV as they're entering junior high. We don't know whether Gardasil will confer lifetime immunity, but from what we know now, it is likely to have a protective effect on a woman through the time in her life when she is most likely to have multple partners.

Maia is also right that if we're going to try for herd immunity against the strains of HPV against which Gardasil protects, the most effective way to do it would be to vaccinate everyone - but there's also the consideration of cost, too. You can see my post I wrote about it earlier for details, but last month there was a study released that looked at the costs versus benefits of different vaccination strategies with Gardasil, and it was in fact vaccinating only girls that had the best cost-to-benefit ratio. It wasn't perfect, but they did predict a 78% reduction in HPV transmission, at a fraction of the cost of vaccinating people of all genders.

An example from the field I work in - animal health - would be vaccination against Brucella abortus in cattle. B. abortus is a bacterium that causes abortion in cattle (and is also transmissible to humans; Florence Nightengale is thought by some to have suffered from Brucellosis, aka "undulant fever," during her last decades as an invalid), and is transmitted through fluids such as milk or semen. Female calves are the only ones vaccinated against Brucella, and through this regimen all but two states in the US are considered Brucellosis-free by the USDA. One, Texas, is a state that imports many animals from countries that have different animal health requirements. The other, Idaho, borders on Yellowstone park, whose bison populations carry Brucella.

brownfemipower wonders why we're simply accepting the idea that HPV causes cervical cancer, and I think the answer is pretty simple: we have good data backing up the assertion, as well as a good idea of how it could be true. If HPV is a virus that can direct your body's cells to divide uncontrollably but benignly as genital warts, it's not a difficult leap to the idea that other strains could cause your body's cells to multiply uncontrollably and malignantly, as is cancer's m.o. She says that she suspects her use of Depo-Provera as contributing to her own cervical cancer, but I don't think that Depo-Provera in itself could reasonably be suspected to cause cervical cancer. There are higher incidences of cervical cancer in users of Depo - and of oral c0ntraceptives - but it's widely suspected that this statistical finding reflects the fact that people already using one type of contraception are less likely to use condoms. If you're still having sex but you're not using condoms, you're still at risk to contract std's.

In the comments to my post about vaccination strategies, I attracted some sort of push-spammer (who came by after looking up Gardasil on Technorati) who left me a nice, organized, bulleted list about the "dangers" of Gardasil that actually left me feeling a little more secure about Gardasil to begin with. I imagine that "stickdog" has been spreading this list all over the blogosphere, so I'll go ahead and address the points one by one, just to have it on the record.
1. GARDASIL is a vaccine for 4 strains of the human papillomavirus (HPV), two strains that are strongly associated (and probably cause) genital warts and two strains that are typically associated (and may cause) cervical cancer. About 90% of people with genital warts show exposure to one of the two HPV strains strongly suspected to cause genital warts. About 70% of women with cervical cancer show exposure to one of the other two HPV strains that the vaccine is designed to confer resistance to.

Well, great. Gardasil is targeted towards the most virulent strains of HPV, the ones most likely to cause cervical cancer and genital warts.
2. HPV is a sexually communicable (not an infectious) virus. When you consider all strains of HPV, over 70% of sexually active males and females have been exposed. A condom helps a lot (70% less likely to get it), but has not been shown to stop transmission in all cases (only one study of 82 college girls who self-reported about condom use has been done). For the vast majority of women, exposure to HPV strains (even the four "bad ones" protected for in GARDASIL) results in no known health complications of any kind.
So far, so good.
3. Cervical cancer is not a deadly nor prevalent cancer in the US or any other first world nation. Cervical cancer rates have declined sharply over the last 30 years and are still declining. Cervical cancer accounts for less than 1% of of all female cancer cases and deaths in the US. Cervical cancer is typically very treatable and the prognosis for a healthy outcome is good. The typical exceptions to this case are old women, women who are already unhealthy and women who don't get pap smears until after the cancer has existed for many years.
Here's where things veer off course. It is true that cervical cancer deaths have declined sharply due to widespread detection of precancerous lesions through pap smears, but cervical cancer is still the second-most common cancer amongst women. Cervical cancer is treatable, though treatment can be drastic, with removal of the cervix and/or uterus, and I don't see any reason to worry less about "old women, women who are already unhealthy and women who don't get pap smears."

4. Merck's clinical studies for GARDASIL were problematic in several ways. Only 20,541 women were used (half got the "placebo") and their health was followed up for only four years at maximum and typically 1-3 years only. More critically, only 1,121 of these subjects were less than 16. The younger subjects were only followed up for a maximum of 18 months. Furthermore, less than 10% of these subjects received true placebo injections. The others were given injections containing an aluminum salt adjuvant (vaccine enhancer) that is also a component of GARDASIL. This is scientifically preposterous, especially when you consider that similar alum adjuvants are suspected to be responsible for Gulf War disease and other possible vaccination related complications.

No, not really. It is difficult to do drug testing involving children, so I don't think that the small proportion of young people involved is very unusual, nor do I think that using a component of Gardasil that is not the active ingredient is a poor control. Test controls need to be selected such that they isolate variables, and removing only the components that confer immunity seems to me the ideal control to use in the test.

5. Both the "placebo" groups and the vaccination groups reported a myriad of short term and medium term health problems over the course of their evaluations. The majority of both groups reported minor health complications near the injection site or near the time of the injection. Among the vaccination group, reports of such complications were slightly higher. The small sample that was given a real placebo reported far fewer complications -- as in less than half. Furthermore, most if not all longer term complications were written off as not being potentially vaccine caused for all subjects.

Okay - so what? Injection-site irritation or infection are very minor complications and were apparently distributed across the control and test subjects.
6. Because the pool of test subjects was so small and the rates of cervical cancer are so low, NOT A SINGLE CONTROL SUBJECT ACTUALLY CONTRACTED CERVICAL CANCER IN ANY WAY, SHAPE OR FORM -- MUCH LESS DIED OF IT. Instead, this vaccine's supposed efficacy is based on the fact that the vaccinated group ended up with far fewer cases (5 vs. about 200) of genital warts and "precancerous lesions" (dysplasias) than the alum injected "control" subjects.
Is this capitalized because it's good news? Cervical cancer is a very preventable disease, and we're seeing exactly how that's true with the point above. It would have been extremely unethical for doctors to have allowed any precancerous lesions to have progressed to cancer or even death, no matter how much more convincing the data would have been for stickdog. The fact is that cervical cancer is not satisfactorily prevented by the CDC recommending that all women have yearly pap smears. Some can't afford to go; some don't want to go, some precancerous lesions fall through the cracks. Women are still dying of cervical cancer, with women of color and poor women represented disproportionately amongst the dead. If Gardasil stands to have a better effect than what we've been able to manage with our flawed health care system and pap surveillance, let's go with Gardasil.
7. Because the tests included just four years of follow up at most, the long term effects and efficacy of this vaccine are completely unknown for anyone. All but the shortest term effects are completely unknown for little girls. Considering the tiny size of youngster study, the data about the shortest terms side effects for girls are also dubious.
As a highly skeptical reading of the data, this is fair enough, though it can be said for any number of drugs that are approved in the US. Vaccines do have the advantage of being small doses that aren't taken every day or every week, so they avoid some of the potential problems that are present with drugs that are used continuously.
8. GARDASIL is the most expensive vaccine ever marketed. It requires three vaccinations at $120 a pop for a total price tag of $360. It is expected to be Merck's biggest cash cow of this and the next decade.
Pap smears are also expensive, and need to be undertaken every year. Additionally, they do not have the advantage of taking possible disease vectors out of the game. I have medical insurance and have been able to have yearly pap smears since I became sexually active. Once, a smear came back with bad results, and while things worked out okay for me, there's really no telling who might have contracted HPV from me, and maybe given it to someone who wasn't insured and doesn't have the opportunity to get yearly pap smears. If I'd been vaccinated against HPV, I would be just as safe, but so would my past sexual partners, and my partners' partners.

Furthermore, the sad fact is that large drug companies deal only in cash cows, and that drug manufacturing is a business that demands profit. It's entirely possible that there are cheaper ways of preventing the spread of HPV, but Gardasil has the advantage of being available right now.

Skepticism is healthy, and I'm sympathetic to Maia and bfp's perspectives. Both of them must know a lot more about racism in medicine and race and gender issues when it comes to reproductive rights than they do about how vaccines work and public health practices. That's fine - we can't specialize in everything. My training in science and inexperience with race and class issues probably make me a little Polyannaish about these issues. Luckily, each of our perspectives can inform the others', and we can thank the blogosphere for facilitating that.

Thoughts?

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