An Update on the HPV Vaccine GARDASIL

In the August 2007 issue of Worst Pills, Best Pills News, we reviewed Merck’s human papilloma virus (HPV) vaccine GARDASIL. We concluded that the vaccine had shown substantial effectiveness in preventing pre-cancerous lesions in the cervix due to the strains of HPV against which the vaccine is targeted (HPV 16 and HPV 18), provided that women were vaccinated before they became infected. We now revisit this controversial vaccine two years later. There have been a number of new developments in the field, which in aggregate support our prior view that the product is safe and effective.

Booster shots not necessary so far

Data currently available do not suggest a need for a booster shot, although this could change as vaccinated women are followed for longer periods of time. (Preapproval trials followed women for up to four years.)

Effectiveness apparently demonstrated in males

A clinical trial has reportedly demonstrated that the vaccine can prevent male genital warts caused by the strains of HPV against which the vaccine is directed (HPV 6 and HPV 11). While this supports the hope that the vaccine will prevent anal cancer in men and penile cancer, these cancers are relatively rare compared to cervical cancer, so vaccination for men is likely to be less cost-effective than for women.

An FDA advisory committee has recommended approval of GARDASIL for males aged 9 to 26, but Food and Drug Administration (FDA) approval has not yet occurred.

Second HPV vaccine likely to enter market

It is likely that GARDASIL will soon have a competitor: CERVARIX, produced by GlaxoSmithKline. This vaccine is active against the same cervical cancer-causing strains of HPV as GARDASIL. It does not, however, provide protection against the genital wart-causing strains that are included in GARDASIL.

An FDA advisory committee has recommended approval of CERVARIX for the prevention of cervical cancer in females aged 10 to 25. The agency has not yet acted on this recommendation. If the vaccine is approved, look for contentious debates over whether the protection against genital warts offered by GARDASIL (but not CERVARIX) justifies the likely more expensive price tag.

Safety data now available

More data on the safety of the vaccine have also been generated. Reviewing international safety data on both GARDASIL and CERVARIX in 2008, Prescrire, a drug company-independent medical journal, concluded that "Reports of serious adverse effects were rare or very rare and it is doubtful whether the vaccine was implicated. The risk/benefit balance for the papillomavirus vaccines in the prevention of high-grade cervical dysplasia [a pre-cervical cancer lesion] in uninfected women remains positive." In other words, the benefits outweigh the risks.

More recently, U.S. government researchers reviewed 12,424 GARDASIL-related adverse events submitted to the FDA by the end of 2008 and published their results in the August 19 Journal of the American Medical Association. Over 23 million doses of the vaccine had been distributed by the end of that year and about one-quarter of all girls aged 13 to 17 in the U.S. had received at least one of the three-shot series. Because of the known limitations of these so-called spontaneously reported data (underreporting, missing clinical details, difficulty in determining that the product caused the adverse effect), the results should be viewed with caution.

Seven hundred and seventy-two reports (6.2%) reports were considered serious. These included 32 deaths, many of which took place after of the patient received multiple vaccines or were clearly due to other causes. The death rate among vaccine recipients was not higher than expected in this age group and did not show a clear pattern that implicated the vaccine.

Most adverse effects, including perennial vaccine-related concerns such as Guillain-Barre Syndrome and autoimmune disorders, did not occur at higher-than-expected rates. However blood clots in the venous system (56 reports of which 31 had sufficient information for clinical review) were increased by five- to seven-fold compared to expected rates, perhaps because of oral contraceptive use and obesity in several cases. Reports of fainting among vaccine recipients were also more common than expected. These can be serious if they lead to falls or fractures, but can be prevented if the patient remains seated for up to 15 minutes following vaccination.

GARDASIL promotion misleading

The same issue of the Journal of the American Medical Association also provided an unfortunately predictable, reminder of the lengths to which Merck was willing to go to promote GARDASIL. The article focused on grants from Merck to professional medical associations such as the American Society for Colposcopy and Cervical Pathology, the Society of Gynecologic Oncologists and the American College Health Association.

Grants from the company encouraged the formation of speakers’ bureaus: physicians willing to go into the physician community and promote GARDASIL, often using company-supplied materials. According to the authors, these materials tended to exaggerate the dangers of cervical cancer, implying that everyone was at equal risk when it is disproportionately a disease of the poor. They also provided an unbalanced picture of the vaccine’s risks and benefits, stressing the benefits more than the risks.

However, even these unethical, if not illegal shenanigans mask the greatest injustice related to GARDASIL. The vast majority of cervical cancer deaths occur in developing countries and Merck’s pricing practices ensure that most women in such countries will never be able to enjoy the vaccine’s cancer-preventing benefits. That’s one thing that hasn’t changed since 2007.