Using health databases in Ontario, Canada, researchers performed a population-based retrospective study comparing one cohort of all girls in grade 8 in 2007/2008 and 2008/2009 who were eligible for publicly funded quadrivalent human papillomavirus (HPV) vaccine, and a second cohort of girls in grade 8 in 2005/2006 and 2006/2007 who did not receive the vaccine. HPV vaccine was licensed in Canada in 2006.

Vaccine exposure was determined for girls in grades 8-9, with outcomes of cervical dysplasia and anogenital warts determined in grades 10-12. A quasi-experimental approach, regression discontinuity, was used to estimate absolute risk difference (RD), relative risk (RR), and the 95% confidence interval (CI) attributable to vaccination and intention-to-treat analysis. Observational studies of vaccine effects are vulnerable to confounding bias because individuals who choose vaccination tend to have different health histories and preventive behaviors than those who do not, and these characteristics are difficult to identify and quantify. Regression discontinuity evaluates the causal effects of interventions in a way that accounts for observed and unobserved confounding, thus facilitating reliable causal inference. Both cohorts were similar for vaccinations other than HPV.

In a total of 260,493 girls, including 131,781 vaccine-ineligible girls and 128,712 vaccine-eligible girls, there were 2,436 cases of cervical dysplasia and 400 cases of anogenital warts. HPV vaccination significantly reduced the incidence of cervical dysplasia with an RD of 5.70/1000 girls (95% CI 9.91 to 1.50), corresponding to a relative reduction of 44% (RR 0.56; 95% CI 0.36 to 0.87). There was a trend attributable to HPV vaccination to decrease anogenital warts (RD 0.83/1000 girls, 95% CI 2.54 to 0.88; RR 0.57, 95% CI 0.20 to 1.58).

COMMENTARY

The quadrivalent HPV vaccine provides protection against four types of HPV that cause 70% of cases of cervical cancer and at least 90% of cases of anogenital warts. The clinical benefit of HPV vaccination for young girls in preventing cervical dysplasia and cancer is generally thought to be observable only during adulthood and later life. This study of a real world population before and after routine HPV vaccination demonstrated that quadrivalent HPV vaccination of girls 13-14 years of age is highly efficacious in preventing vaccine-type cervical dysplasia and anogenital warts even by 17 years of age. Thus, the cost-benefit analysis of HPV vaccination may be even more favorable than previously thought.

Demonstration of benefits of HPV vaccination that are detectable even during late adolescence, before graduation from high school, is solid evidence of the benefits of HPV vaccination in young girls and provides strong justification for not delaying HPV vaccination until girls are older. Girls should be vaccinated at 9-13 years of age before the onset of sexual activity and the associated risk of exposure to HPV.

Some parents have delayed vaccination for their daughters until late adolescence, based on their perceptions of their daughter’s low likelihood of sexual activity. Delay of vaccination based on parent’s preferences is a flawed approach because parents underestimate their child’s sexual experiences. Delayed vaccination will result in missed opportunities for cancer prevention. Universal HPV vaccination of all girls at 9-13 years of age provides the best opportunity for reducing the incidence of cervical dysplasia and, hence, cervical cancer.