Quadrivalent HPV vaccine effectiveness against anogenital warts: A registry-based study of 2,2 million individuals

In 2009, Norway initiated routine quadrivalent HPV (qHPV) vaccination for girls at 12-13 years of age to protect against virus types causing cervical cancer, HPV16/18, and HPV6/11 which cause anogenital warts (AGW). We wanted to investigate qHPV vaccine effectiveness (VE) against AGW in females before and after first AGW episode and to assess the impact of female vaccination in males.

QHPV vaccination and AGW episodes were collected for the time period 2006-2016 for birth cohorts 1975-2003. Cox models were applied to age at first, as well as at second AGW episode. Finally, we estimated the impact of the female vaccination program on unvaccinated males.

The VE against the first episode of AGW was strongly dependent on vaccination age, with hazard ratios (HRs) compared to unvaccinated individuals of 0.2, 0.2, 0.3, 0.5, 1.0, 1.3, and 2.7, for age groups of ⩽13, 14-15, 16-17, 18-19, 20-24, 25-29, and 30+ years at first vaccination, respectively. Among women who had suffered a first episode of AGW, subsequent qHPV vaccination did not protect against a second episode, with HRs of 0.8, 1.0, and 1.4, for age groups of ⩽17, 18-24, and 25+ years at first vaccination. A gradually decreasing AGW risk was seen in unvaccinated male cohorts neighboring the first routinely vaccinated female 1997 cohort.

When administered before 14 years of age, qHPV vaccination reduced the probability of AGW about fivefold. The effect decreased sharply with vaccination age, and was not significant among women vaccinated after age 20 years. QHPV administered after the first AGW episode did not protect against a second AGW episode. Herd effects were indicated in unvaccinated males, as we observed a gradual decrease in AGW rates from the 1993 male birth cohort and onwards.