The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus‐Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16–26 Years

TLDR

The quadrivalent HPV vaccine’s impact on infection and cervical disease caused by 10 nonvaccine oncogenic HPV types that account for over 20 % of cervical cancers was evaluated. The study aimed to assess whether vaccination reduces infection and disease rates associated with these nonvaccine HPV types. In a Phase 3 trial, 17,622 women aged 16–26 were followed for up to four years with periodic cervicovaginal sampling, Pap testing, and HPV typing to monitor infection and disease outcomes. Vaccination lowered the incidence of infection with HPV‑31/33/45/52/58 by 17.7 % and reduced CIN 1–3/AIS by 18.8 %, with additional modest, non‑significant reductions in CIN 2+ for other nonvaccine types. Long‑term surveillance of vaccinated cohorts is required to determine population‑level effects, and the trial is registered under ClinicalTrials.gov identifiers NCT00092521, NCT00092534, and NCT00092482.

Abstract

BackgroundWe evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment MethodsPhase 3 efficacy studies enrolled 17,622 women aged 16–26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6–12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received ⩾1 dose and returned for follow-up were included ResultsVaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1–3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59–related CIN1–3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58–related CIN2 or worse was observed, the estimated reduction was not statistically significant ConclusionsThese cross-protection results complement the vaccine’s prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings Trial registrationClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482