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Natural history of HPV-related oropharyngeal cancer

Research Project

Project/Area Number 19H01062
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionOsaka University

Principal Investigator

INOHARA HIDENORI  大阪大学, 医学系研究科, 教授 (00273657)

Co-Investigator(Kenkyū-buntansha) 森井 英一  大阪大学, 医学系研究科, 教授 (10283772)
谷内田 真一  大阪大学, 医学系研究科, 教授 (20359920)
岡田 随象  大阪大学, 医学系研究科, 教授 (70727411)
二村 圭祐  大阪大学, 医学系研究科, 准教授 (00462713)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
Fiscal Year 2021: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2020: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2019: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Keywords中咽頭癌 / ヒトパピローマウイルス / 前癌病変 / HLA / マイクロバイオーム / リキッドバイオプシー / ctHPVDNA / レセプター
Outline of Research at the Start

ヒトパピローマウイルス(HPV)の感染により発生するHPV関連中咽頭癌は世界的に増加傾向にある。しかし、HPVの感染機構や前癌病変の解明は全く進んでおらず、HPV関連中咽頭癌の予防法は確立されていない。本研究では、レンチウイルスライブラリーを用い感染の端緒となるHPVレセプターを同定するとともに、扁桃摘出患者を対象とした大規模な解析を行い、前癌病変の存在を明らかにし、そのバイオマーカーを確立する。更に、HPV関連中咽頭癌の発癌過程に関与する口腔内の微生物叢(マイクロバーオーム)を明らかにする。本研究によりHPV関連中咽頭癌の予防に向けた施策の構築が可能となる。

Outline of Final Research Achievements

Human papillomavirus (HPV) infects the oropharynx and drive the carcinogenesis, while the mechanism of HPV infection and the natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) remain unknown. We found that SLC25A17 was involved in HPV infection. We also found that HPV mRNA was detectable in oral rinses of cancer-free subjects, who might have HPV-related pre-cancer in the oropharynx. We further found human leukocyte antigenpolymorphism that was associated with HPV-related OPSCC. We established circulating tumor HPV DNA (ctHPVDNA) as a very sensitive biomarker of HPV-related OPSCC. ctHPVDNA was useful in monitoring treatment response and surveying disease recurrence.

Academic Significance and Societal Importance of the Research Achievements

HPV関連中咽頭癌のリスクが高い健常者を対象に含嗽検体のHPV mRNAを評価する検診を行い、HPV mRNAを認める場合には扁桃摘出を行うことによってHPV関連中咽頭癌の発生を予防することが可能となる。HPV関連中咽頭癌が漸増する一方でHPVワクチンの接種が進まない本邦においてその意義は高い。また、HPV関連中咽頭癌は化学放射線療法で加療されることが多いが後遺症が問題となる。治療中のctHPVDNAのクリアランスプロファイルによって治療強度を調整することにより、後遺症を軽減しつつ良好な予後を維持することが可能となる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (4 results)

All 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Peroxisomal membrane protein PMP34 is involved in the human papillomavirus infection pathway.2022

    • Author(s)
      Ito R, Kitamura K, Inohara H, Yusa K, Kaneda Y, Nimura K.
    • Journal Title

      Front Virol.

      Volume: - Pages: 870922-870922

    • DOI

      10.3389/fviro.2022.870922

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV‐related oropharyngeal cancer and cancer of unknown primary2021

    • Author(s)
      Tanaka Hidenori、Suzuki Motoyuki、Takemoto Norihiko、Fukusumi Takahito、Eguchi Hirotaka、Takai Erina、Kanai Haruka、Tatsumi Mitsuaki、Horie Masafumi、Takenaka Yukinori、Yachida Shinichi、Inohara Hidenori
    • Journal Title

      International Journal of Cancer

      Volume: 150 Issue: 1 Pages: 174-186

    • DOI

      10.1002/ijc.33798

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating tumor HPV DNA complements PET‐CT in guiding management after radiotherapy in HPV ‐related squamous cell carcinoma of the head and neck2020

    • Author(s)
      Tanaka Hidenori、Takemoto Norihiko、Horie Masafumi、Takai Erina、Fukusumi Takahito、Suzuki Motoyuki、Eguchi Hirotaka、Komukai Sho、Tatsumi Mitsuaki、Isohashi Fumiaki、Ogawa Kazuhiko、Yachida Shinichi、Inohara Hidenori
    • Journal Title

      International Journal of Cancer

      Volume: 148 Issue: 4 Pages: 995-1005

    • DOI

      10.1002/ijc.33287

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] Diagnostic performance of oral HPV DNA, oral HPV mRNA, and circulating tumor HPV DNA for HPV-related oropharyngeal cancer and cancer of unknown primary.2021

    • Author(s)
      Tanaka H, Inohara H.
    • Organizer
      34th International Papillomavirus Conference
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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