Increasing evidence suggests that 1-dose human papillomavirus (HPV) vaccination may protect significantly against HPV-related disease. We provide nationwide, real-world data on the risk of genital warts (GWs) after <3 vaccine doses.

All Danish women born in 1985–2003 were identified, and individual-level vaccination data were retrieved. The cohort was followed up for first occurrence of GWs until 31 December 2016. Using Poisson regression, we calculated incidence rates (IRs) of GWs per 100 000 person-years and IR ratios (IRRs) with corresponding 95% confidence intervals (CIs) for GWs, according to vaccination status, age at first dose, and calendar time.

The cohort comprised 1 076 945 girls and women, of whom 485 408 were vaccinated. For girls initiating vaccination at age 12–14 years and 15–16 years, 1-dose vaccine effectiveness (VE) was 71% (IRR = 0.29; 95% CI, .22–.38) and 62% (0.38; .29–.49), respectively, compared with unvaccinated girls. In the same age groups, 2-dose VE was 78% (IRR, 0.22; 95% CI, .18–.26) and 68% (0.32; .26–.38), respectively. After 2009, the IRRs for 3 versus 1 dose and 2 versus 1 dose increased towards unity over calendar time, being 0.69 (95% CI, .57–.84) and 0.86 (.68–1.08) in 2016, respectively.

In this study, 1 or 2 doses of quadrivalent HPV vaccine was associated with substantial protection against GWs in girls vaccinated at age ≤16 years. The 1-dose VE approached that of 3 or 2 doses over calendar time, probably reflecting the impact of herd protection.