Efficacy and durability of immediate versus delayed single-dose HPV vaccination for persistent infection among young women in Kenya: a randomized, blinded, cross-over clinical trial

Evidence is needed for single-dose human papillomavirus (HPV) vaccine efficacy (VE) durability to support vaccination guidelines. In this randomized crossover trial (NCT03675256), healthy young women aged 15-20 years, recruited through community-based screening in Kenya, were randomly allocated to immediate nonavalent or bivalent HPV vaccination and delayed control at month 30/36 (age 17-23 years), or immediate control and delayed nonavalent HPV vaccination. Cervical swabs collected every six months were tested for HPV DNA to determine incident persistent HPV infection. The primary outcome was VE at 54 months, estimated among participants who were HPV naive at enrollment vaccination using Cox proportional hazards models with time-varying covariates for HPV vaccine status and time; negative coefficients for time since vaccination indicate durability. For incident persistent HPV 16/18 infections, 104 were detected: 93 pre-crossover and 11 post-crossover; HPV 16/18 VE was 99.3% (95% CI: 96.2,99.9%). For incident persistent HPV 16/18/31/33/45/52/58, 117 infections occurred: 103 pre-crossover and 14 post-crossover; HPV 16/18/31/33/45/52/58 VE was 98.9% (95% CI: 94.9,99.8%). Coefficients for time since vaccination were -0.0014 (95% CI: -0.0027,-0.0002) for HPV 16/18 and -0.0016 (95% CI: -0.0028,-0.0004) for HPV 16/18/31/33/45/52/58. Single-dose HPV vaccination is highly efficacious ( > 98%) and durable over 54 months in young women.