A study of the human papillomavirus (HPV) vaccine in women in Manitoba, Canada, has found that the older a woman is when vaccinated, the less likely she is to be protected against developing precancerous lesions.

The study evaluated Gardasil (Merck), a quadrivalent vaccine that protects against HPV strains 6 and 11, which are linked with risk of genital warts, and strains 16 and 18, which are responsible for 70% of cervical cancers worldwide. The vaccine, which doesn't guarantee protection against cervical cancer, has been in use in Manitoba since 2006, the same year it was approved in the United States, says Salaheddin Mahmud, MD, PhD, Canada research chair in pharmacoepidemiology and vaccine evaluation at the University of Manitoba in Winnipeg and lead researcher on the study.

Gardasil has been evaluated at the population level in the United States and elsewhere, and such studies have shown that it decreases the prevalence of HPV infection, precancerous lesions, and genital warts. However, without data on individual women, the link between these decreases and vaccination is statistically weak. This is the first population-based study to evaluate protection against precancerous lesions in individuals since the vaccine received approval from the U.S. Food and Drug Administration.

In the Manitoba study, reported in the Journal of Clinical Oncology, Mahmud and colleagues used government health records to trace outcomes in 3,541 women vaccinated at age 15 or older between 2006 and 2010, and in 9,594 unvaccinated women. For women vaccinated between the ages of 15 and 17, there was a 35% reduction in the risk of high-grade squamous intraepithelial lesions and a reduction of 21% for low-grade lesions.

The vaccine proved less effective in women vaccinated at age 18 or older. These women had a 23% reduction in the risk of high-grade lesions. However, if they had had an abnormal pap smear prior to vaccination—indicating that they were likely already infected with the virus—there was no reduction in risk.

This kind of study in a real population is an important reality check, says Mahmud. Randomized clinical trials tell “the efficacy of a vaccine if everything went well—if you have the perfect patient and everything is perfect,” he says. This has led some to suggest that the cost of vaccination can be offset by reducing or eliminating cervical cancer screening. Mahmud says these results emphasize the need for continued vigilance in cervical cancer screening.

The results also support the recommendation to vaccinate girls when they are younger, before the onset of sexual activity, and before they have any abnormal pap smears. The vaccine is approved for women up to the age of 26, but it can be given as young as 9. The Centers for Disease Control and Prevention (CDC) in Atlanta, GA, recommends vaccinating girls at age 11 or 12.

“Hopefully people will be vaccinated before the onset of sexual behavior,” says Lauri Markowitz, MD, a medical epidemiologist at the CDC. “The vaccine is not therapeutic, it's preventive.”

Different populations have different rates of exposure to HPV by the time of vaccination, so the effectiveness of the vaccine may vary between populations. But the broader message applies everywhere, says Markowitz: girls should be vaccinated when they are young.