To Vaccinate or Not Vaccinate (Sujatha)

Today's news of Texas governor Rick Perry's making it mandatory for all young girls in Texas to get the anti-cervical vaccine Gardasil has raised a storm of discussion on whether it is indeed desirable to mandate such a thing.
Criticism of the move to make it mandatory ranges from outrage of conservative parents who think it interferes with teaching their daughters how to be 'moral' and abstinent. 'It won't happen to my child, because I'll raise her to be chaste and therefore she can't get the HPV virus', they think."How dare the government force these medical decisions on my children!', to a concern by other groups that the vaccine has not been tested in the long term enough to ensure that the benefits truly outweigh the side effects. It doesn't help that the price of the vaccine is so high that some doctors are charging their patients upfront for the cost of the vaccine, especially since insurance isn't exactly rushing to cover this new vaccine.
As of now, the silver bullet for cervical cancer prevention still remains the humble and inconvenient pap smear test.  Will the vaccine help? Only time and a thorough study of the long term effects in a large population will tell... and the question arises as to whether parents should permit their daughters to be guinea pigs of sorts.

Comments

[stickdog]

The Facts About GARDASIL

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.

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.

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.

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.

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.

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.

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.

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.

These are simply the facts of the situation as presented by Merck and the FDA.

[stickdog]

There are two sides to every discussion, of course. This vaccine does appear to confer some benefits. If I were a sexually active woman who disliked condoms and liked to have multiple sex partners who had not yet been exposed to any of the four strains of HPV that this vaccine protects against, I just might sign myself up.

But that's not the same thing as making this vaccine MANDATORY for a preteen population it was not rigorously tested on a scant 8 months after its initial rush job FDA approval.

Aside from all the known risks of all vaccines, the unknown risks of this three shot regimen for preteens along with their other vaccine load, and the unknown long term risks of this vaccine for all populations, we have to look at cost vs. benefit.

7861 of the placebo subjects contracted 83 cases of HPV 6-, 11-, 16-, 18-related dysplasias during the testing period compared compared to 4 cases among the 7858 subjects who were given GARDASIL. That's after counting out every subject with any prior exposure to these strains. This includes 42 of the less serious HPV 6-, 11- related low grade dysplasias.

Merck has published no data for how many non-HPV 6-, 11-, 16-, 18-related dysplasias were contracted by these subjects over these periods, but some practitioners have commented that they expect the vaccine to protect against 40%-50% of all dysplasias.

In terms of every possible kind of dysplasia for which this vaccine confers protection, Merck's own clinical evidence suggests that this vaccine saved about 10 patients out of each 1000 injected from the painful process of having these dysplasias treated (over the entire course of follow ups which ranged from 18 months to 4 years). Note that the populations for these studies were not preteens but women at the height of their sexual activity. Further note that since the vaccine uses virus-like particles (a new vaccine technology) and is only about five years in testing now, there is no guarantee that it has any long term efficacy.

Of course, the pre-teen population is so less sexually active (and when active, so much less likely to be active with a previously contaminated partner) that I think it would be conservative to estimate that preteens are 5 times less likely to contract HPV dysplasias than the 16 to 26 year olds who were tested by Merck. So instead of saving 10 women per 1000 from painful treatments for HPV dysplasias, this vaccine would save perhaps 2 girls per 1000 from these procedures among the much younger population that Merck and Merck's politicians are targeting for mandatory vaccination.

Do we really want to pursue a public policy that costs $360,000 to vaccinate every 1000 girls while exposing each and every one of these thousand girls to the known adverse short term and largely unknown long terms side effects of three injections of a new vaccine just to save two of the more sexually active of these kids from having to have their dysplasias treated conventionally?

What kind of a risk and cost vs. benefit trade off is that?

Note that nowhere are we discussing actual incidences of cervical cancer because there is no clinical evidence whatsoever that GARDASIL reduces cervical cancer rates, and even if we place our hope in the the fact that it might, cervical cancer is simply not a meaningful health risk for any girl in the target vaccination population who is getting an annual pap smear.

While it is a widely accepted medical theory that HPV "causes" cervical cancer, it's not close to being a fact. Although the vast majority do, many cases of cervical cancer don't show any association with HPV. It's a very good guess that certain strains of HPV are necessary co-factors for certain highly prevalent types of cervical cancer to emerge. The two really bad strains protected for in GARDASIL go hand in hand with 70% of CURRENT cervical cancer cases. My point is that there are 36 nasty strains of HPV screened for currently, and the human body is an ecology. We have no idea how protection against the two strains of HPV that are CURRENTLY most prevalently associated with cervical cancer (typically decades after initial exposure) will affect overall cervical cancer rates far in the future.

What we instead DO know is that current practices of annual pap smears and screening for ALL bad strains of HPV continue to reduce rates of cervical cancer among the US population annually. If all US women received a pap smear every year and were then promptly treated for any abnormal growths encountered, both the cervical cancer contraction and mortality rates would plummet even further to the point where HPV-associated cervical cancer would kill no more than a handful of US women a year. Yes, that is a guess as well, but it's a far better guess than assuming that conferring protection against four of the myriad of current and future strains of harmful HPV will somehow do the trick.

Certainly GARDASIL's benefit data against the four strains of HPV it targets are compelling. HOWEVER, the benefit data against ALL forms of HPV are not published by Merck and estimated by OP-GYNs to be a mixed bag. The benefit data against cervical cancer itself are nonexistent. The long term risk data for any population are nonexistent. There are almost no risk data at all for pre-teens. The fact that the "placebo control" was a shot of alum that was recently shown to cause neural death in mice is particularly problematic in terms of interpreting the small amount of risk data that were gathered.

Studies of the long-term benefits of a new drug or vaccine take a long time. It would take several decades to prove conclusively that this vaccine prevents cervical cancer deaths. So why the rush to make these three injections COMPULSORY for preteens?

Perhaps this would be excusable if GARDASIL conferred protection against HPV generally, but it does not. We have absolutely no way of even guessing how conferring protection against four strains of HPV will affect cervical cancer rates decades down the line. If you do, please quantify the expected benefits in terms of the expected reduction of cervical cancer contraction and mortality rates for the population of US women who get annual pap smears. The only thing you can say about these numbers are that they are unknown and tiny.

I am not trying to stop anyone from signing up themselves or their kids for this. If you want to pay $360 to make your little girl one of Merck's test subjects, please do. As I said, the vaccine shows promise. It may be a life saver for a small segment of the population (especially those too poor or uninformed to get annual pap smears), and it offers protection against most genital warts and a good percentage of HPV dysplasias. The procedures to remove these warts and dysplasias are very painful, so these benefits are compelling. However, the risk and cost vs. benefit profile of this vaccine is not such that it is good public policy to mandate it -- especially not for a pre-teen population on which it has never been sufficiently tested -- even with an "opt out" clause. If Merck wants to make sure that women and parents who want it and can't afford it can get it, they should offer it to low income individuals and families on a sliding scale rather than lobbying state and federal governments to pony up the billions.

[Sujatha]

Stickdog,

Thanks for the exhaustive commentary;)
The red flag, for me, is that Merck is trying to get this vaccinated to be mandatory (legislated or not). That they choose to push it for young girls without additional testing and longer follow-up than 18 months in that specific subpopulation ( 100 or so girls in the 10 yr old age range) seems highly fishy to me. As Ruchira and you have pointed out, it's all definitely related to the Almighty Dollar that Merck hopes to rake in from widening the market for their product by pushing for it to be mandatory, as opposed to letting the free markets deal with it.

[Lorrie]

I am glad to see some support for parents who question this drug. I have an 11 year old who will not be getting the vaccine. I would hate for her to come to me 10-15 years from now and tell me she is sterile because of this drug. What scares me also is a whole generation could be sterile or give birth to babies with birth defects. We don't know because they don't know.