Elucidation of the mechanism of laryngeal papilloma formation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09635
• 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: University of the Ryukyus
• Principal Investigator: Ikegami Taro 琉球大学, 医学(系)研究科(研究院), 助教 (00754409)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 喉頭乳頭腫 / 内反性乳頭腫 / E4 / HPV-6 / HPV-11 / EGFR / ヒトパピローマウイルス / IP

Outline of Final Research Achievements

We determined the amount of viral DNA in HPV-11-infected papilloma, the expression of nine viral genes, and the localization of each gene within the papilloma. In addition, we generated an antibody against HPV-11 E4 protein to clarify whether E4, the most expressed gene, is translated into a protein and functions. The results showed that the cells expressing E4 protein in papilloma were structurally disrupted, and the nuclei of the cells were filled with progeny viruses, suggesting that E4 is involved in maintaining and releasing progeny viruses. In addition, we investigated whether HPV infection and mutations in exon 20 of the epidermal growth factor receptor (EGFR) gene are associated with inverted papilloma (IP) formation, suggesting that high-risk HPV is involved in malignant transformation from IP to SCC, but that inframe insertion in exon 20 of EGFR gene is related to IP formation.

Free Research Field

耳鼻咽喉・頭頸部外科学

Academic Significance and Societal Importance of the Research Achievements

HPV-11関連乳頭腫においてHPV-6と同様にE4、E5a、E5bの３遺伝子の発現が約９割を占めていることを明らかにした。我々が開発した抗HPV-6抗体と抗HPV-11E4抗体はHPV-6E4とHPV-11E4を識別でき、交差反応性のない優れた抗体である。内反性乳頭腫（IP）においてEGFRのExon20の領域のinframe insertionが鍵となっていること、IPからSCCへの悪性転化に一部に高リスク型HPVが関与する可能性を示した。さらにde novo SNSCCの約3割においては高リスク型HPVががん化に関与する可能性が高い。