The Early Benefits of Human Papillomavirus Vaccination on Cervical Dysplasia and Anogenital Warts

BACKGROUND: Despite widespread promotion of quadrivalent human papillomavirus (qHPV) vaccination for young girls, there is limited information on the vaccine's real-world effectiveness and none on the effectiveness of qHPV vaccination programs. We assessed the impact of the qHPV vaccine and Ontario's grade 8 qHPV vaccination program on cervical dysplasia and anogenital warts (AGW). METHODS: By using administrative health databases of Ontario, Canada, we identified a population-based retrospective cohort of girls in grade 8 before (2005/2006-2006/2007) and after (2007/2008-2008/2009) program implementation. Vaccine exposure was ascertained in grades 8 to 9 and outcomes in grades 10 to 12. A quasi-experimental approach known as regression discontinuity was used to estimate absolute risk differences (RDs), relative risks (RRs), and 95% confidence intervals (CIs) attributable to vaccination and program eligibility (intention-to-treat analysis). RESULTS: The cohort comprised 131 781 ineligible and 128 712 eligible girls (n = 260 493). We identified 2436 cases of dysplasia and 400 cases of AGW. Vaccination significantly reduced the incidence of dysplasia by 5.70 per 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). Program eligibility also had a significant protective effect on dysplasia: RD -2.32/1000 (95% CI -4.02 to -0.61); RR 0.79 (95% CI 0.66 to 0.94). Results suggested decreases in AGW attributable to vaccination (RD -0.83/1000, 95% CI -2.54 to 0.88; RR 0.57, 95% CI 0.20 to 1.58) and program eligibility (RD -0.34/1000, 95% CI -1.03 to 0.36; RR 0.81, 95% CI 0.52 to 1.25). CONCLUSIONS: This study provides strong evidence of the early benefits of qHPV vaccination among girls aged 14 to 17 years, offering additional justification for not delaying vaccination.