title: Increased radiosensitivity of HPV-positive head and neck cancers: Molecular basis and therapeutic perspectives.
abstract: Human papillomavirus driven head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), are characterized by a significant survival advantage over their HPV-negative counterparts. Although the reasons behind this are still not fully elucidated, it is widely accepted that these tumors have a higher response to ionizing radiation that might explain their favorable outcomes. Potential underlying intrinsic mechanisms include impaired DNA repair abilities, differences in activated repopulation-signaling pathways and cell cycle control mechanisms. The role of the microenvironment is increasingly highlighted, particularly tumor oxygenation and the immune response. Recent studies have shown a distinct pattern of intratumoral immune cell infiltrates, according to HPV status, and have suggested that an increased cytotoxic T-cell based antitumor immune response is involved in improved prognosis of patients with HPV-positive OPSCC. These significant milestones, in the understanding of HPV-induced HNSCC, pave the way to new therapeutic opportunities. This article reviews the current evidence on the biological basis of increased radiosensitivity in HPV-positive HNSCC and discusses potential therapeutic implications.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif, France. Electronic address: haitham.mirghani@gustaveroussy.fr.
authors.forename: Haïtham
authors.initials: H
authors.lastname: Mirghani
authors.affiliation: Department of Otolaryngology, Peterborough City Hospital and Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Furrat
authors.initials: F
authors.lastname: Amen
authors.affiliation: Department of Radiation Oncology, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif, France.
authors.forename: Yungan
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Radiation Oncology, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif, France; Université Paris Sud, Faculté de Médecine, Kremlin Bicêtre 94270, France; INSERM U1030 Molecular Radiotherapy, Cancer Research Institute, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Department of Radiation Oncology, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif, France; Université Paris Sud, Faculté de Médecine, Kremlin Bicêtre 94270, France; INSERM U1030 Molecular Radiotherapy, Cancer Research Institute, Villejuif, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000532:radiotherapy* / Q000821:virology; D004260:DNA Repair; D006258:Head and Neck Neoplasms / Q000150:complications / Q000532:radiotherapy* / Q000821:virology; D052162:Human papillomavirus 16; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000532:radiotherapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D011836:Radiation Tolerance; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Head and neck cancer; Human papillomavirus 16; Oropharyngeal; Oropharynx; Radiation; Treatment