Explaining the mechanism of high sensitivity for radiotherapy in human papilloma related oropharyngeal cancer.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: Nishimura Goshi 横浜市立大学, 医学部, 准教授 (30381510)
• Co-Investigator(Kenkyū-buntansha): 佐野 大佑 横浜市立大学, 医学部, 講師 (10620990) ; 高橋 秀聡 横浜市立大学, 医学研究科, 客員研究員 (50727196) ; 折舘 伸彦 横浜市立大学, 医学研究科, 教授 (90312355)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 中咽頭癌 / ヒト乳頭腫ウイルス / 放射線感受性

Outline of Final Research Achievements

Most of the HPV-related head and neck cancer patients are infected by HPV 16. According to HPV 16 infection produces p16 protein, we analyzed the installed location and the alteration of methylation prior to p16 and cyclin D1 proteins production. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV 16 genomes at the integration breakpoints. The HPV 16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV 16 DNA became methylated.

Free Research Field

頭頸部腫瘍

Academic Significance and Societal Importance of the Research Achievements

HPV陽性中咽頭癌は飲酒・喫煙歴のない若年者層で増加傾向にある一方、放射線治療への反応は良好である。放射線への感受性が良好な機序を解明することで治療後の長期に亘る晩期有害事象を軽減できる可能性が期待される。ヒトゲノムと取り込まれたHPVゲノムのメチル化の程度に関する傾向が示されたことで、今後は遺伝子発現やシグナル伝達との関連性の解明につなげたいと考えている。