Objectives: Quadrivalent HPV vaccine efficacy against vaccine type related cervical intraepithelial neoplasia (CIN) or external genital lesions (EGL [includes vulvar or vaginal intraepithelial neoplasia (VIN and VaIN) and condyloma]) in adult women was previously shown to be 92.4% (95% CI: 49.6, 99.8). As this trial has now concluded, we evaluated the efficacy of quadrivalent HPV vaccine against CIN or EGL in women aged 24-45 through the end-of-study.

Methods: 3,819 24-45 year old women received quadrivalent vaccine or placebo at day 1, and months 2 and 6. Ascertainment of HPV-related cervical and genital disease was accomplished via Pap testing, genital inspection and cervicovaginal sampling. Analyses were conducted in a per-protocol population (women who received 3 doses of vaccine/placebo within 1 year of enrollment, were naïve to the relevant HPV types at day 1, and remained free of infection through the completion of the vaccination regimen). Mean follow-up time per subject was 3.8 years, representing an additional 1.6 years of follow-up when compared to earlier analyses.

Results: The efficacy of quadrivalent HPV vaccine in the prevention of HPV6/11/16/18-related CIN or EGL was 95.7% (95% CI: (73.4, 99.9). The one case among vaccinees was an HPV16-related CIN2 which was included in the original analysis. Efficacy against HPV6/11/16/18-related persistent infection was 89.6% (95% CI: 79.3, 95.4). Vaccine efficacy against the incidence of abnormal Pap smears related to HPV 16 or 18 in a per-protocol population was 96.3% (95% CI: 77.7, 99.9). Among vaccinated women naïve to 14 HPV types at baseline (including vaccine HPV types) there was a 12.6%, 16.3% and 30.9% reduction seen in the occurrence of colposcopy, biopsy and any definitive therapy, respectively.

Conclusions: These data demonstrate that qHPV vaccine is highly effective in preventing HPV6/11/16/18-related persistent infection, CIN, EGL, and abnormal Pap smears in women aged 24 to 45 naïve to vaccine HPV types.