The Dollars and Sense of Vaccination for Cervical Cancer

Dollar for dollar, vaccinating U.S. girls age 11 or 12 against human papillomavirus (HPV) is a better health investment than vaccinating boys or women older than 30, concluded the authors of two recent cost-­effectiveness studies.

Published in October, the studies were timed to inform U.S. guidelines, said lead author Jane Kim, HSPH assistant professor of health decision science. They also coincided with U.S. approval of a second HPV vaccine.

Soon after the studies were published, the Advisory Committee on Immunization Practices (ACIP) for the U.S. Centers for Disease Control and Prevention (CDC), voted to permit but not recommend routine vaccination of males age 9 to 26, Kim said.

“In the U.S., there is a movement toward evidence-based healthcare practice and comparative effectiveness,” said Kim, who presented the study results to the ACIP in June 2009. “Cost-effectiveness is one of many important inputs into the decision-making process.”

Since 2007, the ACIP has recommended routine vaccination for girls age 11 or 12 and catch-up shots for females age 13 to 26, ideally before potential exposure to HPV, which is transmitted through sexual contact.

The results of the two studies apply to the two available vaccines, Gardasil (manufactured by Merck) and Cervarix (GlaxoSmithKline Biologicals). Both vaccines protect against the two strains, HPV 16 and 18, estimated to cause 70 percent of all cervical cancers, and Gardasil also protects against two noncancerous strains, HPV 6 and 11, which cause genital warts. The U.S. Food and Drug Administration approved Gardasil in 2006 for females. In October 2009, the FDA approved Gardasil for males and Cervarix for females only.

Both vaccines show promising results in protecting unexposed females against precancerous lesions caused by the HPV types targeted by the vaccines. But the vaccines do not work in people who already have infection with those HPV types. At the population level, the cost-effectiveness of HPV vaccination diminishes in older females, Kim and HSPH colleague Sue Goldie reported in the Aug. 21, 2008, New England Journal of Medicine, because the probability of being sexually active—and therefore exposed to HPV—increases as women age. About one quarter of U.S. girls are sexually active by age 15, increasing to 70 percent by age 18 and more than 90 percent by age 26, according to the 2002 National Survey of Family Growth.

It will be decades before anyone will be able to measure the real impact on cervical cancer or on other HPV-linked genital, oral and throat cancers. In the absence of sufficient evidence, scientists can use computer models of the natural history of the disease to test the impacts and costs and benefits of health strategies, as well as harness the uncertainties to predict possible future scenarios. The results help policymakers come to rational choices about medical interventions.

In the latest two studies, Kim and Goldie, who is the Roger Irving Lee professor of public health at HSPH, extended their modeling and cost-effectiveness analyses of HPV vaccination to U.S. boys and women older than 30. In one study, adding HPV vaccination to regular cervical cancer screening for women age 35 to 45 years costs anywhere from $116,950 to $381,590 per quality-adjusted life year (QALY), the researchers report in the Oct. 20, 2009, Annals of Internal Medicine. A rough threshold of good value for the money ranges from $50,000 to $100,000 per QALY, Kim said, but can vary depending on other considerations.

These findings reflect that although HPV infection is quite common in sexually active women, cervical cancer risk is low in the U.S., in part because of the aggressive screening policy of Pap smears every one to three years, Kim said. Regular testing helps prevent cervical cancer by finding it at an early, treatable stage. Even with effective vaccines, cervical screening will still be necessary since 30 percent of cervical cancers are caused by HPV types not protected by the vaccines.

In the study comparing males and females, boys generally had cost-­effectiveness ratios higher than $100,000 per QALY, Kim and Goldie reported in the Oct. 8, 2009, online British Medical Journal (BMJ).

The findings are consistent with another independent study by Austrian researchers, but differ from a Merck study that found vaccinating boys was cost-effective. New information may change results, Kim said, including how long immunity lasts, how many people receive vaccinations, and what happens if people do not finish the full three-dose course of vaccination.

“The health economic implications are clear—good coverage of females obviates the need to vaccinate boys,” wrote Philip Castle of the National Cancer Institute, and Isabel Scarinci of the University of Alabama at Birmingham, in an accompanying editorial in BMJ. They write, “The best policy is to ensure that preadolescent females are vaccinated worldwide.”

For more information, students may contact Jane Kim at jkim@hsph.harvard.edu or Sue Goldie at sgoldie@hsph.harvard.edu.

Conflict Disclosure: The authors declare no conflicts of interest

Funding Sources: The National Cancer Institute, Centers for Disease Control and Prevention, American Cancer Society, Bill and Melinda Gates Foundation; the authors are solely responsible for the content of this work.