Introduction Quadrivalent human papillomavirus (HPV) vaccine was first licensed for use in the United States (US) for females in June 2006. Vaccination uptake has increased over time; among girls aged 13–17 years, coverage with ≥ 1 dose was 25% in 2007 and 60% in 2014. Population effectiveness of HPV vaccination against anogenital warts (AGW) has been difficult to estimate because few data sources link vaccination and diagnosis information.

Methods Using healthcare claims data for 2003–2014, we created a cohort of 2 70 481 females aged 9–17 in 2006 who were continuously enrolled (1) for at least 1.5 years prior to June 2006 and (2) subsequent to June 2006 through at least age 18. AGW diagnoses, and age at receipt of first and second dose (≥6 months subsequent to first dose) of quadrivalent vaccine, were ascertained. Doses received after first AGW diagnosis, or at age ≥ 18, were not considered. Cumulative risk (hazard) of AGW was compared for unvaccinated females and those who received 1 or 2 doses.

Results Median age at first vaccination was 15 years; only 28% of the cohort received ≥ 1 dose. Vaccination at age 9–12 was highly protective; vaccine effectiveness (VE), computed as [1-hazard ratio]*100, was 87% (p<0.001) for 1 dose and 92% (p<0.001) for 2 doses. VE among those first vaccinated at age 13–14 was similar for 1 and 2 doses (83% and 80% respectively, p<0.001 for both estimates), but was lower if the second dose was received at age 15–17 (65%, p<0.001). Among those first vaccinated at age 15–17, VE was much lower (21% for 1 dose and 42% for 2 doses), but was still significantly protective (p<0.001 for both estimates).

Conclusion VE estimates among girls vaccinated prior to age 15 in this privately-insured population were comparable to estimates reported for adult intention-to-treat clinical trial subjects. Vaccination at age ≥ 15, while protective, was less effective, particularly for those receiving only 1 dose. Increasing US vaccination coverage prior to age 15 should result in enhanced population-level effectiveness against AGW.