Elucidation of prognostic factors for HPV-associated oropharyngeal carcinoma and prediction of treatment response by liquid biopsy.

• Project/Area Number: 19K09883
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Hokkaido University
• Principal Investigator: Mizumachi Takatsugu 北海道大学, 医学研究院, 客員研究員 (00507577)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 頭頸部癌 / 中咽頭癌 / HPV / 耳鼻咽喉科学

Outline of Research at the Start

HPV関連中咽頭癌は欧米はもとより本邦においても急増している。HPV関連中咽頭癌は放射線治療や化学療法に対する感受性が良好で予後も良好である。このためHPV関連中咽頭癌に対して治療強度を下げることが可能であるかを検証する臨床試験が進められているが、HPV関連中咽頭癌のなかには予後不良例も存在する。予後良好な症例に対しては治療強度を下げ、予後不良例には治療強度を高める個別化治療が可能となれば生存率とQOLの向上が期待できる。本研究はHPV関連中咽頭癌における予後規定因子を同定すること、治療前検体より予後予測を可能にすることを目的とし、個別化医療への道標とするものである。

Outline of Final Research Achievements

HPV-associated oropharyngeal carcinomas had a significantly higher rate of Schlafen family member 11 (SLFN11) positivity than non-associated oropharyngeal carcinomas. HPV infection is involved in the high expression of SLFN11 and that SLFN11 is involved in the favorable treatment sensitivity of HPV-associated oropharyngeal carcinoma.

Academic Significance and Societal Importance of the Research Achievements

HPV感染により発症した中咽頭癌は喫煙、飲酒により発症した中咽頭癌とは臨床病態や分子生物学的特徴が大きく異なる。HPV関連中咽頭癌は非関連癌に比べて予後は良好であるが、一部のHPV関連中咽頭癌においては遠隔転移をきたし予後不良症例も存在する。HPV関連中咽頭癌は本邦のみならず世界的にも発症数は急増傾向にあり、発症や転移機構の解明が待たれるところである。本研究においてHPV関連中咽頭癌とSchlafen family member 11 (SLFN11)遺伝子との関係を明らかにすることができた意義は大きいと思われる。

Research Products

• [Journal Article] Macroscopic and multiple metastases in sentinel lymph node biopsy are respectively associated with poor prognosis in early oral cancer (2023)
  • Author(s): Kondo Takahito、Tsukahara Kiyoaki、Kawakita Daisuke、Yoshimoto Seiichi、Miura Kouki、Sugasawa Masashi、Chikamatsu Kazuaki、Matsuzuka Takashi、Oze Isao、Kitamura Morimasa、Murakami Yoshiko、Otozai Shinji、Shinozaki Takeshi、Ohba Shinichi、Araki Koji、Mizumachi Takatsugu、et al
  • Journal Title: International Journal of Clinical Oncology Volume: 28 Issue: 4 Pages: 512-520
  • DOI: 10.1007/s10147-023-02305-1
  • Peer Reviewed / Open Access
• [Journal Article] Schlafen family member 11 indicates favorable prognosis of patients with head and neck cancer following platinum-based chemoradiotherapy (2023)
  • Author(s): Hamada Seijiro、Kano Satoshi、Murai Junko、Suzuki Takayoshi、Tsushima Nayuta、Mizumachi Takatsugu、Suzuki Masanobu、Takashima Tsuyoshi、Taniyama Daiki、Sakamoto Naoya、Fujioka Yoichiro、Ohba Yusuke、Homma Akihiro
  • Journal Title: Frontiers in Oncology Volume: 12 Pages: 978875-978875
  • DOI: 10.3389/fonc.2022.978875
  • Peer Reviewed / Open Access
• [Journal Article] Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients (2021)
  • Author(s): Fujima Noriyuki、Shimizu Yukie、Yoshida Daisuke、Kano Satoshi、Mizumachi Takatsugu、Homma Akihiro、Yasuda Koichi、Onimaru Rikiya、Sakai Osamu、Kudo Kohsuke、Shirato Hiroki
  • Journal Title: The Journal of Medical Investigation Volume: 68 Issue: 3.4 Pages: 354-361
  • DOI: 10.2152/jmi.68.354
  • NAID: 130008115660
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma (2021)
  • Author(s): Takayoshi Suzuki, Satoshi Kano, Masanobu Suzuki, Shinichiro Yasukawa, Takatsugu Mizumachi, Nayuta Tsushima, Kanako C Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Akihiro Homma
  • Journal Title: Front Oncol Volume: - Pages: 1-12
  • DOI: 10.3389/fonc.2020.603717
  • Peer Reviewed / Open Access
• [Journal Article] Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck (2021)
  • Author(s): Jun Taguchi, Yasushi Shimizu, Shin Ariga, Tomohiro Goda, Yoshihito Ohhara, Rio Honma, Takuro Noguchi, Satoshi Takeuchi, Ichiro Kinoshita, Toraji Amano, Takatsugu Mizumachi, Satoshi Kano, Miki Takahara, Takahisa Abe, Akihiro Homma, Hirotoshi Dosaka-Akita
  • Journal Title: Int J Clin Oncol Volume: 26 Issue: 1 Pages: 51-58
  • DOI: 10.1007/s10147-020-01788-6
  • Peer Reviewed
• [Journal Article] The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma (2021)
  • Author(s): Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
  • Journal Title: Auris Nasus Larynx Volume: 48 Issue: 1 Pages: 131-137
  • DOI: 10.1016/j.anl.2020.06.014
  • NAID: 120007189934
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients (2020)
  • Author(s): Yasuda K, Minatogawa H, Dekura Y, Takao S, Tamura M, Tsushima N, Suzuki T, Kano S, Mizumachi T, Mori T, Nishioka K, Shido M, Katoh N, Taguchi H, Fujima N, Onimaru R, Yokota I, Kobashi K, Shimizu S, Homma A, Shirato H, Aoyama H.
  • Journal Title: Journal of Radiation Research Volume: 62 Issue: 2 Pages: 329-337
  • DOI: 10.1093/jrr/rraa130
  • Peer Reviewed / Open Access
• [Journal Article] Optimization of therapeutic strategy for p16‐positive oropharyngeal squamous cell carcinoma: Multi‐institutional observational study based on the national Head and Neck Cancer Registry of Japan (2020)
  • Author(s): Saito Yuki、et al.
  • Journal Title: Cancer Volume: 126 Issue: 18 Pages: 4177-4187
  • DOI: 10.1002/cncr.33062
  • Peer Reviewed / Open Access
• [Journal Article] Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin. (2019)
  • Author(s): Hamauchi S, Yokota T, Mizumachi T, Onozawa Y, Ogawa H, Onoe T, Kamijo T, Iida Y, Nishimura T, Onitsuka T, Yasui H, Homma A.
  • Journal Title: Int J Clin Oncol. Volume: 24 Issue: 5 Pages: 468-475
  • DOI: 10.1007/s10147-018-01392-9
  • NAID: 120006777913
  • Peer Reviewed
• [Journal Article] Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study. (2019)
  • Author(s): Fujima N, Shimizu Y, Yoshida D, Kano S, Mizumachi T, Homma A, Yasuda K, Onimaru R, Sakai O, Kudo K, Shirato H
  • Journal Title: Cancers Volume: 11 Issue: 6 Pages: 800-800
  • DOI: 10.3390/cancers11060800
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The utility of MRI histogram and texture analysis for the prediction of histological diagnosis in head and neck malignancies (2019)
  • Author(s): Fujima Noriyuki、Homma Akihiro、Harada Taisuke、Shimizu Yukie、Tha Khin Khin、Kano Satoshi、Mizumachi Takatsugu、Li Ruijiang、Kudo Kohsuke、Shirato Hiroki
  • Journal Title: Cancer Imaging Volume: 19 Issue: 1 Pages: 5-5
  • DOI: 10.1186/s40644-019-0193-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 頭頸部癌化学放射線療法におけるEPA高配合栄養機能食品(プロシュア)の有用性の検討 (2019)
  • Author(s): 水町貴諭, 加納里志, 本間明宏, 赤澤美樹子, 長谷川千春, 城陽子, 岡本千秋, 熊谷聡美, 西村雅勝, 高崎裕代, 武田宏司, 安田耕一, 湊川英樹, 出倉康裕, 鬼丸力也, 白土博樹, 福田諭
  • Journal Title: 癌と化学療法 Volume: 46 Pages: 685-689
  • Peer Reviewed
• [Journal Article] 【甲状腺・副甲状腺-知りたいこと・知っておかねばならないこと】腺腫様甲状腺腫の取り扱い方 (2019)
  • Author(s): 水町貴諭
  • Journal Title: JOHNS Volume: 35 Pages: 735-738
• [Journal Article] Treatment outcomes of local advanced external auditory canal squamous cell carcinomas (2019)
  • Author(s): 加納里志, 森田真也, 中丸裕爾, 水町貴諭, 対馬那由多, 鈴 崇祥, 中薗彬, 福田篤, 安田耕一, 鬼丸力也, 白土博樹, 本間明宏
  • Journal Title: Toukeibu Gan Volume: 45 Issue: 3 Pages: 300-304
  • DOI: 10.5981/jjhnc.45.300
  • NAID: 130007744532
  • ISSN: 1349-5747, 1881-8382
  • Peer Reviewed
• [Book] ガイドライン外来診療2019 (2019)
  • Author(s): 水町貴諭、本間明宏
  • Total Pages: 718
  • Publisher: 日経メディカル開発
  • ISBN: 9784931400924