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The effectiveness of HPV vaccine and the breakthrough cases

Research Project

Project/Area Number 20K09677
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionShowa University

Principal Investigator

Mamiko Onuki  昭和大学, 医学部, 准教授 (20573744)

Co-Investigator(Kenkyū-buntansha) 松本 光司  昭和大学, 医学部, 教授 (30302714)
柊元 巌  国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (70291127)
Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHPVワクチン / 子宮頸癌 / 子宮頸部上皮内腫瘍 / 子宮頸がん / 子宮頸がんワクチン(HPVワクチン) / HPV / CIN, AIS / HPVワクチン接種年齢 / 初交年齢 / ヒトパピローマウイルス / 子宮頸癌ワクチン / 子宮頸部上皮内病変(CIN) / 子宮頸部上皮内腺癌(AIS) / ブレイクスルー症例 / 子宮頸部上皮内病変 / CIN
Outline of Research at the Start

本研究では、1) 定期接種プログラムが定める適切な年齢(12-16歳) で子宮頸癌ワクチンを接種したにも関わらずHPV16/18陽性CIN・子宮頸癌を発症した若年日本人女性(=ブレイクスルー症例) を対象にまず初交年齢・ワクチン接種時年齢を聴取することで接種時に実は既感染であったと考えられる患者の割合を推定すること、2) 初交前に適切にワクチン接種を行っていた症例ではHPVゲノム解析・pseudovirionを用いた中和活性測定を行い、現行のワクチンでは予防できない変異ウイルス(variant) を探索する。

Outline of Final Research Achievements

Cases of HPV16/18-positive cervical cancer and precancerous lesions after HPV vaccination in Japanese women under 40 years of age registered in “Study for Monitoring project for the Impact of National HPV vaccinaTion program in Japan” were defined in the broad sense. Breakthrough cases were defined as cases in which HPV16/18-positive cervical cancer or precancerous lesions developed after HPV vaccination. We examined the relationship between the age of first sexual intercourse and the age of vaccination in these cases, and examined the proportion of cases who were already infected at the time of vaccination. More than 100 breakthrough cases in the broad sense were enrolled during the study period. In the population for which the relationship between age of vaccination and age of first intercourse was known, all cases were vaccinated later than the age of first intercourse and could be assumed to have been previously infected at the time of vaccination.

Academic Significance and Societal Importance of the Research Achievements

HPVワクチン接種後かつHPV16/18陽性の子宮頸部病変患者を対象に接種年齢、初交年齢など詳細に解析した。ワクチンの恩恵を最大に受けるためには接種時期が重要であることを日本人女性のデータとして学会発表や論文により公表できたと考えている。また本邦での定期接種年齢の上限が16歳であることが、世界と比較しても遅い上に、本邦でも16歳接種ではワクチン効果が一部不十分となる集団がいることをデータとして示し、定期接種年齢上限の引き下げについても学会や講演会などで提言を行った。

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (24 results)

All 2024 2023 2022 2021 2020

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Declining Prevalence of Human Papillomavirus Co‐Infections Among Young Japanese Women With Cervical Cancer and Its Precursors2024

    • Author(s)
      Yoshiizumi E, Onuki M、Kukimoto I, Matsumoto K, the MINT Study Group
    • Journal Title

      Journal of Medical Virology

      Volume: 96 Issue: 12

    • DOI

      10.1002/jmv.70096

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the <scp>MINT</scp> study2023

    • Author(s)
      Onuki Mamiko,Kukimoto Iwao,Matsumoto Koji et al, for the MINT Study Group
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 11 Pages: 4426-4432

    • DOI

      10.1111/cas.15943

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intra-Patient Genomic Variations of Human Papillomavirus Type 31 in Cervical Cancer and Precancer2023

    • Author(s)
      Kogure Gota、Tanaka Kohsei、Matsui Tomoya、Onuki Mamiko、Matsumoto Koji、Iwata Takashi、Kukimoto Iwao
    • Journal Title

      Viruses

      Volume: 15 Issue: 10 Pages: 2104-2104

    • DOI

      10.3390/v15102104

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age at first sexual intercourse among young women with invasive cervical cancer: implications for routine vaccination against human papillomavirus in Japan2023

    • Author(s)
      Nakazawa Hiroshi、Yamaguchi Satoshi、Onuki Mamiko、Kitai Miho、Yahata Hideaki、Aoki Yoichi、Horie Koji、Mimura Takashi、Okadome Masao、Kato Hisamori、Takehara Kazuhiro、Kamiura Shoji、Shigeta Shogo、Matsumoto Koji、For MINT Study II Group
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 53 Issue: 6 Pages: 530-533

    • DOI

      10.1093/jjco/hyad017

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] わが国におけるHPVワクチン接種プログラムの有用性と課題2023

    • Author(s)
      小貫麻美子
    • Journal Title

      日本女性医学学会雑誌

      Volume: 30 Pages: 476-478

    • Related Report
      2023 Research-status Report
  • [Journal Article] Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions2022

    • Author(s)
      Kogure Gota、Onuki Mamiko、Hirose Yusuke、Yamaguchi-Naka Mayuko、Mori Seiichiro、Iwata Takashi、Kondo Kazunari、Sekizawa Akihiko、Matsumoto Koji、Kukimoto Iwao
    • Journal Title

      Virology Journal

      Volume: 19 Issue: 1 Pages: 157-157

    • DOI

      10.1186/s12985-022-01894-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia2022

    • Author(s)
      Kukimoto Iwao、Onuki Mamiko、Yaegashi Nobuo、Matsumoto Koji、MINT Study Group
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 52 Pages: 1428-1434

    • DOI

      10.1093/jjco/hyac127

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ancient Evolutionary History of Human Papillomavirus Type 16, 18 and 58 Variants Prevalent Exclusively in Japan.2022

    • Author(s)
      Tanaka K, Kogure G, Onuki M, Matsumoto K, Iwata T, Aoki D, Kukimoto I.
    • Journal Title

      Viruses

      Volume: 14 Issue: 3 Pages: 464-464

    • DOI

      10.3390/v14030464

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women.2022

    • Author(s)
      Onuki M, Matsumoto K, et al. for The MINT Study Group.
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 4 Pages: 1428-1434

    • DOI

      10.1111/cas.15270

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program.2022

    • Author(s)
      Onuki M, Matsumoto K, et al. for The Mint Study Group.
    • Journal Title

      Vaccines (Basel)

      Volume: 10 Issue: 2 Pages: 181-181

    • DOI

      10.3390/vaccines10020188

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan2020

    • Author(s)
      Onuki M, Matsumoto K, Iwata T, Yamamoto K, Aoki Y, Maenohara S, Tsuda N, Kamiura S, Takehara K, Horie K, Tasaka N, Yahata H, Takei Y, Aoki Y, Kato H, Motohara T, Nakamura K, Ishikawa M, Kato T, Yoshida H, Matsumura N, Nakai H, Shigeta S, Takahashi F, Noda K, Yaegashi N, Yoshikawa H.
    • Journal Title

      Cancer Sci

      Volume: 117 Issue: 7 Pages: 2546-2557

    • DOI

      10.1111/cas.14445

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Papillomavirus (HPV) Genotyping Assay Suitable for Monitoring the Impact of the 9-Valent HPV Vaccine2020

    • Author(s)
      Kukimoto Iwao、Matsumoto Koji、Takahashi Fumiaki、Iwata Takashi、Tanaka Kohsei、Yamaguchi-Naka Mayuko、Yamamoto Kasumi、Yahata Hideaki、Nakabayashi Makoto、Kato Hisamori、Tsuda Naotake、Onuki Mamiko、Yaegashi Nobuo、MINT Study II Group
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 251 Issue: 4 Pages: 287-294

    • DOI

      10.1620/tjem.251.287

    • NAID

      130007884397

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Declining prevalence of human papillomavirus co-infections among young Japanese women with cervical cancer and its precursors2024

    • Author(s)
      Yoshiizumi E, Onuki M, Kukimoto I, Takahashi F, Iwata T, Yamaguti S, Kanao H, Ariyoshi K, Yahata H, Yoshikawa H, Yaegashi N, Matsumoto K for MINT Study Group.
    • Organizer
      Asia-Oceania Research Organization in Genital Infection and Neoplasia 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human papillomavirus vaccine effectiveness among young Japanese women:Results from the MINT study.2024

    • Author(s)
      Onuki M
    • Organizer
      Asia-Oceania Research Organization in Genital Infection and Neoplasia 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HPVワクチンの子宮頸がん予防効果 我が国初のエビデンス.2024

    • Author(s)
      小貫麻美子, 松本光司, 八重樫伸生, 吉川裕之
    • Organizer
      第76回日本産科婦人科学会学術講演会
    • Related Report
      2024 Annual Research Report
  • [Presentation] ヒトパピローマウイルス31型の全長ゲノム配列の統合的解析 (Integrated analysis of the full-genome sequence of human papillomavirus 31)2023

    • Author(s)
      柊元 巌, 小暮剛太, 小貫麻美子, 岩田 卓, 松本光司
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 日本人女性の子宮頸部病変から検出されたHPV67型の全長ウイルスゲノム解析2023

    • Author(s)
      小暮剛太, 小貫麻美子, 廣瀬佑輔, 岩田 卓, 近藤一成, 関沢明彦, 松本光司
    • Organizer
      第75回日本産科婦人科学会学術講演会
    • Related Report
      2023 Research-status Report
  • [Presentation] 若年子宮頸癌患者における初交年齢 HPVワクチン定期接種における対象年齢は適切か?2023

    • Author(s)
      中澤浩志, 山口 聡, 小貫麻美子, 八重樫伸生, 松本光司.
    • Organizer
      第75回日本産科婦人科学会学術講演会
    • Related Report
      2023 Research-status Report
  • [Presentation] 日本人女性におけるHPVワクチンの有効性 MINT studyの結果(Human papillomavirus vaccine effectiveness among Japanese women: Results from the MINT study)2022

    • Author(s)
      小貫麻美子
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会 基調講演1 HPV Vaccine in Asia and Japan(英語)
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 我が国におけるHPVワクチン接種プログラムの有用性と課題2022

    • Author(s)
      小貫麻美子
    • Organizer
      第37回日本女性医学学会学術集会学術奨励賞受賞講演
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 子宮頸部上皮内腫瘍におけるHPV52検出率は日本の東西で異なる2022

    • Author(s)
      柊元巌, 小暮剛太, 小貫麻美子, 八重樫伸生, 松本光司
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 我が国におけるHPVワクチンの直接予防効果と集団免疫効果:MINTスタディ10年の軌跡2022

    • Author(s)
      小貫麻美子, 渡利英道, 島田宗昭, 藤原寛行, 佐藤豊実, 藤原恵一, 横田治重, 岩田卓, 石川光也, 金尾祐之 , 加藤久盛, 平島泰之, 万代昌紀, 松村謙臣, 上浦祥司, 山口聡, 中村圭一郎, 竹原和宏, 矢幡秀昭, 岡留雅夫, 牛嶋公生, 本原剛志, 青木陽一, 八重樫伸生, 松本光司
    • Organizer
      第74回日本産科婦人科学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] HPVタイピング・ウイルスゲノム解析によるCIN進展リスク評価と我が国における9価ワクチンの効果予測2021

    • Author(s)
      小貫麻美子
    • Organizer
      第73回日本産科婦人科学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] Whole-genome analysis of possibly carcinogenic HPV67 isolated from Japanese women WITH CERVICAL CANCER/PRECANCER2021

    • Author(s)
      Gota Kogure, Mamiko Onuki, Takashi Iwata, Koji Matsumoto, Iwao Kukimoto
    • Organizer
      34th International Papillomavirus Conference - IPVC 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2026-01-16  

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