A report by the Costa Rican HPV Vaccine Trial Group published in the Journal of the American Medical Association (Aug. 15) describes a controlled randomized trial sponsored by the National Cancer Institute testing GlaxoSmithKline's HPV vaccine. The subjects included 2,189 Costa Rican women aged 18 to 25 who had tested positive for HPV DNA at the time of recruitment.

The study sheds light on the very limited potential benefit of the vaccine--given that most HPV infections clear spontaneously within 6 months to 2 years. [1] [2] The authors acknowledge this, as they report the negative finding of the study:

"There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group."

Their conclusion the HPV vaccine does not offer a therapeutic benefit for women already infected with HPV: "In women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections." Of equal interest is disclosure that the U.S. government has a financial interest in the HPV vaccine. The following Financial Disclosures are reported: "Drs Schiller and Lowy report that they are named inventors on US government-owned HPV vaccine patents that are licensed to GSK and Merck and are entitled to limited royalties as specified by federal law. Dr Dubin is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial. No other financial disclosures were reported." [Link]

This raises serious questions about the abuse of power to mandate a vaccine in which the government has a financial interest.

The safety issues of the vaccine remain unclear: "Since the trial is ongoing and investigators and site personnel have no access to safety data by treatment group, we also did not evaluate the safety profile of the vaccine in this analysis."

This study finding validates one of the concerns raised by the vaccine's primary investigator, Dr. Diane Harper, from Dartmouth, who strongly disapproved of Merck's effort to persuade states to mandate the vaccine for school age girls because of safety and efficacy concerns--including the consequences of vaccinating women already infected.

Dr. Harper's more detailed concerns were validated by an important JAMA editorial in May, 2007. The JAMA editors weighed in against mandatory HPV vaccination for the following reasons:

1. Human papillomavirus is not a highly infectious airborne disease, which is the paradigm for the exercise of compulsory vaccination. There is no immediate risk of rapid transmission of HPV in schools, as is the case, for example, with measles.

2. High risk types of HPV--such as 16 and 18--have a relatively low prevalence in the U.S. (3.4% of all HPV infections),

3. The HPV vaccine does not create herd immunity. Because the HPV vaccine is not immediately necessary to prevent harm to others, it does suggest that compulsory measures need to be more carefully thought through.

4. Not all women who are infected with high-risk HPV types will develop cervical cancer. Approximately 90% of women with new HPV infections clear the infection within 2 years.

5. It is important to emphasize that the vaccine is supported by limited efficacy and safety data. Clinical trials have thus far involved a relatively small population (2,000 participants) for a limited period of follow-up (5 years).

6. The vaccine has not been evaluated for efficacy among younger girls (aged 9 to 15 years). Yet, if the vaccine were required nationwide, it would be administered to some 2 million girls and young women, most of them between 11 and 12 years old and some as young as 9 years old.

7. The longer-term effectiveness and safety of the vaccine still need to be evaluated among a large population, and particularly among younger. A clinician can honestly provide only the following information to a 12-year-old girl to obtain her assent: "The 3 injections will probably protect you from an infection that you can only get from sexual contact, but research has not shown how long the protection will last or whether it might have bad effects on your health."

8. Another important consideration is how vaccine recipients would be compensated if they incurred serious adverse effects in the future as a result of a vaccine that the state required.

9. The rush to make HPV vaccination mandatory in school aged girls presents ethical concerns and is likely to be counterproductive. Legislation to make HPV vaccine mandatory has undermined public confidence and created a backlash among parents.

10. Merck, the manufacturer of the HPV quadrivalent vaccine, lobbied legislatures to make the vaccine mandatory before withdrawing its campaign when it became controversial. Since the manufacturer stands to profit from widespread vaccine administration, it is inappropriate for the company to finance efforts to persuade states and public officials to make HPV vaccinations mandatory, particularly so soon after the product was licensed.

11. Private wealth should never trump public health.

12. There is also the question of cost - who will pay for the mandated HPV vaccine? What other public health services would society have to forgo because of the cost?

The estimated cost of quadrivalent HPV vaccine is $360 for a 3-course series, making it among the most expensive of all vaccines. [Link]

Reference:

1. Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423-428. 2. Schiffman M, Herrero R, Desalle R, et al. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005;337(1):76-84