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

Mamiko Onuki; Kasumi Yamamoto; Hideaki Yahata; Hiroyuki Kanao; Koji Horie; Katsuyuki Konnai; Ai Nio; Kazuhiro Takehara; Shoji Kamiura; Naotake Tsuda; Yuji Takei; Shogo Shigeta; Hidekatsu Nakai; Hiroyuki Yoshida; Takeshi Motohara; Tatsuya Kato; Keiichiro Nakamura; Junzo Hamanishi; Nobutaka Tasaka; Mitsuya Ishikawa; Nobuhiro Kado; Yusuke Taira; Mayuyo Mori; Takashi Iwata; Fumiaki Takahashi; Iwao Kukimoto; Hiroyuki Yoshikawa; Nobuo Yaegashi; Koji Matsumoto; For The Mint Study Group

doi:10.3390/vaccines10020188

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

Vaccines (Basel). 2022 Jan 25;10(2):188. doi: 10.3390/vaccines10020188.

Authors

Mamiko Onuki¹, Kasumi Yamamoto², Hideaki Yahata³, Hiroyuki Kanao⁴, Koji Horie⁵, Katsuyuki Konnai⁶, Ai Nio⁷, Kazuhiro Takehara⁸, Shoji Kamiura⁹, Naotake Tsuda¹⁰, Yuji Takei¹¹, Shogo Shigeta¹², Hidekatsu Nakai¹³, Hiroyuki Yoshida¹⁴, Takeshi Motohara¹⁵, Tatsuya Kato¹⁶, Keiichiro Nakamura¹⁷, Junzo Hamanishi¹⁸, Nobutaka Tasaka¹⁹, Mitsuya Ishikawa²⁰, Nobuhiro Kado²¹, Yusuke Taira²², Mayuyo Mori²³, Takashi Iwata²⁴, Fumiaki Takahashi²⁵, Iwao Kukimoto²⁶, Hiroyuki Yoshikawa¹⁹, Nobuo Yaegashi¹², Koji Matsumoto¹, For The Mint Study Group

Affiliations

¹ Department of Obstetrics and Gynecology, School of Medicine, Showa University, Tokyo 142-8666, Japan.
² Department of Gynecologic Oncology, Hyogo Cancer Center, Akashi 673-0021, Japan.
³ Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Department of Gynecology, Cancer Institute Hospital, Tokyo 135-0063, Japan.
⁵ Department of Gynecology, Saitama Cancer Center, Saitama 362-0806, Japan.
⁶ Department of Gynecology, Kanagawa Cancer Center, Yokohama 241-8515, Japan.
⁷ Gynecology Service, NHO Kyushu Cancer Center, Fukuoka 811-1395, Japan.
⁸ Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan.
⁹ Department of Gynecology, Osaka International Cancer Institute, Osaka 541-8567, Japan.
¹⁰ Department of Obstetrics and Gynecology, School of Medicine, Kurume University, Kurume 830-0011, Japan.
¹¹ Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke 329-0498, Japan.
¹² Department of Obstetrics and Gynecology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
¹³ Department of Obstetrics and Gynecology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan.
¹⁴ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan.
¹⁵ Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
¹⁶ Department of Obstetrics and Gynecology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
¹⁷ Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan.
¹⁸ Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
¹⁹ Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
²⁰ Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
²¹ Division of Gynecology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan.
²² Department of Obstetrics and Gynecology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan.
²³ Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
²⁴ Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
²⁵ Division of Medical Engineering, Department of Information Science, Iwate Medical University, Yahaba 028-3694, Japan.
²⁶ Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.

Abstract

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.

Keywords: adenocarcinoma in situ; cervical cancer; cervical intraepithelial neoplasia; human papillomavirus; vaccination.

Abstract

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