Protection Against Persistent HPV-16/18 Infection After Different Number of Doses of Quadrivalent Vaccine in Girls and Young Women: A Randomized Clinical Trial
Mené au Canada sur 3 356 enfants âgés de 9 à 11 ans, cet essai randomisé évalue la persistance d'une infection par le papillomavirus HPV16 ou HPV18 en fonction du nombre de doses du vaccin quadrivalent (2 ou 3)
There are no randomized studies comparing the long-term effectiveness of a 2-dose schedule (administered at 0 and 6 months) of quadrivalent human papillomavirus vaccine (4vHPV) with a 2 + 1–dose schedule (administered at 0, 6, and 60 months) given to preadolescents for the prevention of persistent HPV-16 and HPV-18 infection.To evaluate whether a 2-dose 4vHPV schedule is noninferior to a 2 + 1–dose schedule for preventing persistent HPV-16 and HPV-18 infection up to 13 years after the first dose.This 2-arm, parallel, noninferiority, randomized clinical trial (RCT), called ICI-VPH (Impact of HPV Immunization Schedules Against HPV), was conducted in Québec, Canada, from 2013 to 2021. Eligible participants were girls who had received 2 doses of 4vHPV, 6 months apart when they were aged 9 to 11 years, 5 years prior to trial recruitment. Efficacy-evaluable population analysis was conducted between April 2023 and June 2024.Participants were randomized 1:1 to the 2-dose or 2 + 1–dose groups. The 2 + 1–dose group received a booster dose of 4vHPV at the recruitment visit. Both groups were instructed on how to self-collect a vaginal sample, provided an initial vaginal swab, and completed an online questionnaire.The primary outcome was persistent HPV-16 and HPV-18 infection, defined as the presence of HPV-16 or HPV-18 DNA in 2 consecutive vaginal samples self-collected 5 to 15 months apart.Among the 3356 participants, the mean (SD) age at enrollment was 14.8 (0.4) years, and 2867 (85.4%) were French Canadian individuals. Of the 3364 participants initially randomized, 8 (0.2%) withdrew immediately after randomization, 1675 (49.8%) were assigned to the 2-dose group, and 1681 (50.0%) were assigned to the 2 + 1–dose group. Of the 16 989 genotyping tests analyzed, 31 (0.2%) detected vaccine-type HPV-6, -11, -16, and -18. Only 1 participant in the 2 + 1–dose group (0.1%) had a time-limited persistent HPV-16 infection.This clinical trial found that the incidence of HPV-16 and HPV-18 infection was low with both the 2-dose and 2 + 1–dose 4vHPV schedules. A 2-dose schedule provided robust protection against persistent HPV-16 and HPV-18 infection for up to 13 years, suggesting that a booster dose administered at 60 months would not provide additional benefit.ClinicalTrials.gov Identifier: NCT02009800
JAMA Network Open , article en libre accès, 2025