Noninferiority of One HPV Vaccine Dose to Two Doses

Abstract

Background: Multidose human papillomavirus (HPV) vaccination is efficacious, yet the vaccine has been underused globally. Emerging data suggest that a single dose may provide protection. Whether a single dose of HPV vaccine would provide similar protection to two doses is uncertain.

Methods: In this trial, we assessed whether one dose of an HPV vaccine was noninferior to two doses. Girls 12 to 16 years of age were randomly assigned, in a 1:1:1:1 ratio, to receive one or two doses of a bivalent HPV vaccine or one or two doses of a nonavalent HPV vaccine. The primary end point was new HPV type 16 or 18 infection occurring from month 12 to month 60 and persisting for at least 6 months. The prespecified noninferiority margin was 1.25 infections per 100 participants. We also assessed vaccine effectiveness by comparing HPV16 or HPV18 infection among the trial participants with that among girls and women enrolled in a nonrandomized survey.

Results: A total of 20,330 participants were enrolled and underwent randomization, and 3005 unvaccinated participants were enrolled in the survey. The noninferiority analysis showed that one vaccine dose was noninferior to two doses in preventing HPV16 or HPV18 infection. The rate difference between one and two doses of the bivalent vaccine was -0.13 infections per 100 participants (95% confidence interval [CI], -0.45 to 0.15; P<0.001 for noninferiority), and the difference between one and two doses of the nonavalent vaccine was 0.21 infections per 100 participants (95% CI, -0.09 to 0.51; P<0.001 for noninferiority). The vaccine effectiveness was at least 97% in each of the four trial groups. No safety concerns were identified.

Conclusions: One dose of either a bivalent or nonavalent HPV vaccine provided protection against HPV16 or HPV18 infection and was not inferior to two doses. (Funded by the National Cancer Institute and others; ESCUDDO ClinicalTrials.gov number, NCT03180034.).