Statistical analysis
HPV infection
PERSISTENT INFECTION, EVENTS, SENSITIVITY, HPV INFECTION
The study was powered for the 18-month analysis, which included follow-up through 18 months and has been previously publishedWe used Cox proportional hazards models stratified by study site to estimate the hazard ratios (HRs) of the interventions versus control for the primary and sensitivity analyses. Models for the sensitivity analyses used crude incidence rate ratios instead of the Cox model when no events were observed in a group. Follow-up was calculated as days since the month 3 visit for the primary analysis and days since month 6 for the extended-sensitivity analysis until the first persistent infection. Participants who did not reach this outcome were censored at the last study visit with HPV testing where they did not meet the criteria for persistent infection. VE was expressed as 1 − HR (or relative risk). The log-rank test stratified by study site was used to calculate the Participants included in the primary analysis tested HPV DNA negative (external genital/lateral vaginal, and cervical swabs) at enrollment and at month 3, by self-collected vaginal swab and HPV antibody negative at enrollment in the mITT cohort. The ITT included all randomized participants. For inclusion in the HPV 16/18 mITT cohort, participants were HPV 16/18 naive. Similarly, for the HPV 16/18/31/33/45/52/58 mITT cohort, participants were HPV 16/18/31/33/45/52/58 naive. Participants without swabs after month 3 did not contribute follow-up time in the primary analysis. Participants in the bivalent vaccine group were excluded from the HPV 16/18/31/33/45/52/58 analysis as the study was not powered to detect cross-protection. Participants who seroconverted to HIV during follow-up are included in analyses.Sensitivity analyses were planned for the following subsets: participants who tested HPV DNA negative at enrollment and month 3, regardless of antibody status at enrollment (sensitivity cohort) and participants who tested HPV DNA negative at enrollment, month 3, and month 6 and antibody negative at enrollment (extended-sensitivity cohort); the sensitivity cohort was a less conservative definition of an HPV-naive cohort and the extended-sensitivity cohort more closely matched the analysis cohort for HPV vaccine licensure trials. The extended-sensitivity cohort excluded participants who might have had prevalent HPV infection at enrollment that was not detected. Safety was assessed among all participants; the three groups were compared using Fisher’s exact test. Exploratory analysis evaluated cross-protection of the bivalent vaccine against HPV 31/33/45. We performed all analyses using SAS software, v.9.4 (SAS Institute) and R (v.4.2.2).An independent Data Safety and Monitoring Board was constituted to review study progress, participant safety and the primary outcome, and met annually. The trial is registered at ClinicalTrials.gov (