Background The GARDASIL long-term follow-up (LTFU) study is an ongoing extension of a pivotal randomised, placebo-controlled, double-blind, 4-year study to investigate the safety, immunogenicity, and effectiveness of quadrivalent Human Papillomavirus vaccine (qHPV) on the incidence of HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2 or worse in 16–23-year-old women (Protocol 015).

Methods Follow-up of subjects will be accomplished in two ways: (1) registry-based follow-up for effectiveness data as well as safety data including but not limited to deaths, cancer, and hospitalisations; (2) active follow-up for blood collection for immunogenicity assessments at years 5 and 10 of the LTFU study. Effectiveness and safety analyses will occur approximately 2 years following completion of Protocol 015 and approximately every 2 years thereafter for 10 years. The current report represents the first of these efficacy and safety analyses. Cohort 1 included approximately 2700 subjects who received qHPV vaccine at the start of Protocol 015. Cohort 2 consists of approximately 2100 subjects who received placebo at the start of Protocol 015 and qHPV vaccine prior to entry into the LTFU. Vaccine effectiveness against HPV 16/18-related CIN 2 or worse was estimated by calculating the expected incidence of CIN 2/3 or worse in an unvaccinated (placebo) cohort using historical registry data. The primary analysis approach was per-protocol.

Results There were 1080 subjects that contributed to the follow-up period out of a total of 2195 eligible subjects in the per-protocol population in Cohort 1. In these subjects there were no cases of HPV 16/18-related CIN 2 or worse observed. There were also no cases of HPV 6/11/16/18-related CIN, vulvar cancer, and vaginal cancer observed. However, the follow-up time in person-years is insufficient to make a definitive statement about the effectiveness of the qHPV vaccine for the current time period.

Conclusions The qHPV vaccine shows a trend of continued protection in women who were vaccinated up to 7 years previously, although there is as yet insufficient data to confirm that protection is maintained. The qHPV vaccine continues to be generally safe and well tolerated up to 6 years following vaccination.