Zaravinos Apostolos
Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological Sciences, University of Cyprus, 1678 Nicosia, Cyprus. Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, 14145 Huddinge, Sweden.
Oncotarget. 2014 Jun 30;5(12):3956-69. doi: 10.18632/oncotarget.1934.
Human papilloma virus (HPV)-associated head and neck carcinoma is quite heterogeneous and most of the tumors arise in the oral cavity, oropharynx, hypopharynx and larynx. HPV was just recently recognized as an emerging risk factor for oropharyngeal squamous cell carcinoma (OSCC). HPV(+) tumors represent 5-20% of all head and neck squamous-cell carcinomas (HNSCCs) and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. Different carcinogenic mechanisms are most likely implicated in cervical and oropharyngeal carcinogenesis. The most certain carcinogenic genotype for the head and neck region and the most common high-risk HPV genotype, HPV-16, is frequently detected in OSCC. A combination of p16INK4A expression and molecular detection of HPV DNA is the gold standard for the viral identification in tissue and exfoliated cell samples. Differences in the biology of HPV(+) and HPV(-) OSCC may have implications for the management of patients. New immunotherapy drugs based on the release of the co-inhibitory receptors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) have currently emerged. The goal of therapeutic cancer vaccination is inculcation of a persistent, tumor antigen-specific T cell response which kills tumor cells. The efficacy of the current HPV vaccines, Cervarix and Gardasil, in preventing HPV-related HNSCC is at present unknown. Treatment de-escalation is recommended as the current management of HPV-induced HNSCCs.
人乳头瘤病毒（HPV）相关的头颈部癌具有高度异质性，大多数肿瘤发生于口腔、口咽、下咽和喉部。HPV最近才被确认为口咽鳞状细胞癌（OSCC）的一个新出现的危险因素。HPV（+）肿瘤占所有头颈部鳞状细胞癌（HNSCC）的5%-20%，占口咽来源肿瘤的40%-90%，其发生率因地理区域、人群、环境相关鳞状细胞癌的相对患病率及检测方法不同而有很大差异。不同的致癌机制很可能与宫颈癌和口咽癌的发生有关。头颈部区域最确定的致癌基因型以及最常见的高危HPV基因型HPV-16，在OSCC中经常被检测到。p16INK4A表达与HPV DNA分子检测相结合是组织和脱落细胞样本中病毒鉴定的金标准。HPV（+）和HPV（-）OSCC生物学特性的差异可能对患者的治疗产生影响。基于共抑制受体细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性死亡蛋白1（PD-1）释放的新型免疫治疗药物目前已出现。治疗性癌症疫苗接种的目标是诱导持续的、肿瘤抗原特异性的T细胞反应以杀死肿瘤细胞。目前尚不清楚现有的HPV疫苗希瑞适和佳达修在预防HPV相关HNSCC方面的疗效。建议将降阶梯治疗作为目前HPV诱导的HNSCC的治疗方法。
