Chen Allen M
Department of Radiation Oncology, Irvine, Chao Family Comprehensive Cancer Center, University of California, 101 The City Drive, Building 23, Orange, CA, 92868, USA.
Curr Oncol Rep. 2025 May;27(5):634-641. doi: 10.1007/s11912-025-01666-2. Epub 2025 Apr 11.
While the oncogenic potential of HPV has been well-established in other disease sites (e.g. cervix, vulva, anus), it is increasingly evident that a significant proportion of oropharyngeal cancer cases are related to the virus. Although considerable progress has been made in the understanding of this disease with respect to its underlying biology and clinical behavior, numerous questions persist. From a therapeutic standpoint, HPV-positive oropharyngeal cancer has been shown to be more radiosensitive than HPV-negative disease. However, how HPV mediates this radiosensitivity is relatively uncertain.
Given that it has been firmly established that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite response to radiation and can be treated with less-than-standard doses, logical questions pertain to how HPV confers this benefit to infected patients. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, multiple theories have been proposed. Indeed, it is likely that no single explanation exists for the increased radiosensitivity, and instead, HPV likely exerts its influence through a cascade of activated pathways at both the cellular level and tumor microenvironment. As will be discussed in this review, the proposed mechanisms for HPV-induced radiation response have generally centered on the disruption of such cellular pathways as DNA repair, cell cycle checkpoints, metabolic-induced stress, immunology, and cancer stem cells. Given that HPV-positive oropharyngeal cancer is increasingly recognized as a public health problem, the search to better understand its unique biological radiosensitivity has important societal and treatment-related implications.
虽然人乳头瘤病毒（HPV）的致癌潜力在其他疾病部位（如子宫颈、外阴、肛门）已得到充分证实，但越来越明显的是，相当一部分口咽癌病例与该病毒有关。尽管在了解这种疾病的潜在生物学特性和临床行为方面已经取得了相当大的进展，但仍存在许多问题。从治疗角度来看，HPV阳性口咽癌已被证明比HPV阴性疾病对放疗更敏感。然而，HPV如何介导这种放射敏感性相对不确定。
鉴于HPV阳性口咽癌患者因其对放疗的出色反应而预后显著改善，并且可以用低于标准剂量进行治疗，合理的问题是HPV如何将这种益处赋予受感染患者。虽然HPV阳性口咽癌放射敏感性提高的确切原因尚不清楚，但已经提出了多种理论。事实上，对于放射敏感性增加可能不存在单一的解释，相反，HPV可能通过细胞水平和肿瘤微环境中一系列激活的途径发挥其影响。如本综述将讨论的，HPV诱导的辐射反应的拟议机制通常集中在DNA修复、细胞周期检查点、代谢诱导的应激、免疫学和癌症干细胞等细胞途径的破坏上。鉴于HPV阳性口咽癌越来越被认为是一个公共卫生问题，寻求更好地理解其独特的生物学放射敏感性具有重要的社会和治疗意义。
