Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program

Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1–3 (CIN1–3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among “unvaccinated” cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged <40 years, newly diagnosed with CIN/AIS during 2012–2021 for time trends. Declining trends in HPV16/18 prevalence over 9 years were observed in CIN1 (36.0–10.0%, P(trend) = 0.03) and CIN2–3/AIS (62.5–36.4%, P(trend) = 0.07) among women aged <25 years. HPV16/18 prevalence in CIN1 and CIN2–3/AIS diagnosed at age 20–24 years was lower in 1994–1999 birth cohorts compared with 1988–1993 birth cohorts (4.5% vs. 25.7% for CIN1 and 40.0% vs. 58.1% for CIN2–3/AIS, both p = 0.04). Significant reduction in HPV16/18 prevalence among young unvaccinated women with CIN1 and CIN2–3/AIS suggests herd effects of HPV vaccination in Japan.