Effect of Prior 9-Valent Human Papillomavirus Vaccination on Subsequent Lower Genital Tract Dysplasia After Cervical Excisional Surgery

Abstract

Objective: To assess the efficacy of prior 9-valent human papillomavirus (9vHPV) vaccination on risk of subsequent cervical, vaginal, and vulvar disease after a cervical excisional procedure for cervical squamous intraepithelial lesion (SIL) in a retrospective clinical trial analysis.

Methods: Women aged 16-26 years were randomized to three-dose regimens of 9vHPV vaccine, quadrivalent HPV (4vHPV) vaccine, or placebo in three double-blind efficacy trials: a study of 9vHPV vaccine compared with 4vHPV vaccine ( ClinicalTrials.gov , NCT00543543) and two historic placebo-controlled 4vHPV vaccine studies ( ClinicalTrials.gov , NCT00092521 and NCT00092534). Incidence of subsequent condyloma, cervical, vulvar, or vaginal SIL was compared between 9vHPV vaccine and controls in women who underwent cervical excisional surgery after vaccination and had 6 months or more of follow-up after surgery. For HPV31/33/45/52/58-related endpoints, the control group was 4vHPV vaccine (from 9vHPV vaccine trial); for HPV6/11/16/18 analysis, the control group was historic placebo (from 4vHPV vaccine trials).

Results: This analysis included 295 9vHPV vaccine, 722 4vHPV vaccine, and 493 historic placebo recipients who underwent cervical surgery after a median of 1.7 years (range 0.1-4.4 years) after dose 1. Subsequent to surgery, HPV6/11/16/18-related SIL incidence was reduced by 95.4% (95% CI, 74.7-99.8%) with prior 9vHPV vaccine relative to historic placebo (1.3 vs 29.0/1,000 person-years, respectively); HPV31/33/45/52/58-related SIL incidence was reduced by 86.3% (95% CI, 47.5-97.8%) with 9vHPV vaccine compared with 4vHPV vaccine (2.7 vs 19.4/1,000 person-years, respectively). The incidence of high-grade SIL was numerically lower in the 9vHPV vaccine group relative to control, but this was not statistically significant (HPV6/11/16/18 related 69.6% reduction [95% CI, -133.5% to 98.7%]; HPV31/33/45/52/58 related 82.7% [95% CI, -29.2% to 99.2%]).

Conclusion: Among female trial participants who underwent cervical excisional surgery, prior vaccination with 9vHPV vaccine (ie, 0.1-4.4 years before surgery) reduced the incidence of subsequent cervical and lower genital tract dysplasia.

Clinical trial registration: ClinicalTrials.gov , NCT00543543, NCT00092521, NCT00092534.

Trial registration: ClinicalTrials.gov NCT00543543 NCT00092521 NCT00092534 NCT03979014.