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