Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women: Open follow-up of a randomized clinical trial up to 4 years post-vaccination

In this open, extended follow-up study (NCT00929526, Clinicaltrials.gov), we evaluated the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine efficacy, immunogenicity and safety up to 4 years after first vaccination in Japanese women aged 20–25 years. In the initial randomized, double-blind study (NCT00316693), 1040 women received the study vaccine or hepatitis A control vaccine; 752 women were included in the follow-up study. In women from the according-to-protocol efficacy cohort (ATP-E), who were initially seronegative for the HPV type analyzed, no cervical intraepithelial neoplasia (CIN) grade 1 or greater (CIN1+) cases associated with HPV-16/18 were reported in the HPV group, while in the control group, 5 cases were identified in extended follow-up analyses (vaccine efficacy [VE] 100% [95% CI: −3.7–100]) and 8 cases in combined initial and follow-up studies analyses (VE 100% [42.2–100]). In the ATP-E, VE against CIN1+ and CIN2+ associated with high-risk HPV types reached 66.4% (21.6–87.1) and 83.0% (22.1–98.2) in extended follow-up analyses, and 63.4% (28.8–82.3) and 77.3% (30.4–94.4) in analyses of combined studies, respectively. During the 4-year period, protection against CIN1+ and CIN2+, irrespective of the HPV type, was 56.7% (32.8–72.6) and 54.9% (20.5–75.3) in women receiving ≥1 vaccine dose, regardless of baseline serostatus (total vaccinated cohort [TVC]) and 61.0% (11.8–84.2) and 73.9% (1.1–95.3) in women naïve to HPV infection at baseline (TVC-naïve), respectively. The high VE observed in Japanese women, accompanied by a sustained immune response and a clinically acceptable safety profile, support findings of large, international trials.