The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma
The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma
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DOI：
10.1007/s10147-016-1005-x
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发表时间：
2016-10-01
影响因子：
3.3
通讯作者：
Oridate, Nobuhiko
中科院分区：
文献类型：
--
作者：
Sano, Daisuke;Oridate, Nobuhiko
头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症。最近，口咽癌（OPC）的发病率与HNSCC相比显著增加，HNSCC与吸烟或饮酒或两者兼而有之有关。这一增长主要是由于全球人乳头瘤病毒（HPV）相关口咽癌（HPV-OPCs）数量的增加。HPV-OPC具有几个独特的特征，包括与酒精和吸烟相关的HNSCC相比，年轻患者的表现，对治疗的反应率更高，预后更好。HPV感染状态现在是OPC患者生存的独立预后因素。一般而言，HPV癌蛋白E6和E7是通过p53和pRb失活引起HPV相关癌症的起始和进展的主要病毒因子。然而，其他因素的改变，包括基因组不稳定性，HPV DNA整合和表观遗传学改变，可能对肿瘤转化和肿瘤进展同样重要。基因组不稳定性和外部环境因素对通过高危HPV感染引发宫颈癌发展的影响已得到充分表征，但对HPV诱导HNSCC致癌的潜在机制知之甚少。本文综述了HPV相关癌症的生物学和分子机制，包括特别关注HPV相关HNSCC基因组改变的综合表征的几项最新研究。
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recently, the incidence of oropharyngeal cancer (OPC) has increased markedly in comparison to that of HNSCC, which is associated with the use of tobacco or alcohol or both. This increase has resulted mainly from the global rise in the number of human papillomavirus (HPV)-related oropharyngeal cancers (HPV-OPCs). HPV-OPC has several unique characteristics, including presentation in younger patients, better response rates to treatment, and better prognosis compared to alcohol- and smoking-related HNSCC. HPV infection status is now an independent prognostic factor for survival in patients with OPC. In general, HPV oncoproteins E6 and E7 are the primary viral factors responsible for the initiation and progression of HPV-related cancers via the inactivation of p53 and pRb. However, alterations in additional factors, including genomic instability, HPV DNA integration, and epigenetic alterations, could be equally important for neoplastic transformation and tumor progression. The impact of genomic instability and external environmental factors on the initiation of cervical cancer development through high-risk HPV infection has been well characterized, although less is known about the mechanism underlying HPV-induced carcinogenesis in HNSCC. This review provides an overview of the biology and molecular mechanisms of HPV-related cancers, including a particular focus on several recent studies on the comprehensive characterization of genomic alterations in HPV-associated HNSCC.