Human Papillomavirus in Head and Neck Cancer: Its Role in Pathogenesis and Clinical Implications
Human Papillomavirus in Head and Neck Cancer: Its Role in Pathogenesis and Clinical Implications
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DOI：
10.1158/1078-0432.ccr-09-0784
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发表时间：
2009-11-15
影响因子：
11.5
通讯作者：
Gillison, Maura L.
中科院分区：
文献类型：
--
作者：
Chung, Christine H.;Gillison, Maura L.
头颈部鳞状细胞癌（HNSCC）是第六常见的癌症，全世界每年约有400，000例发病。虽然头颈癌的主要危险因素仍然是吸烟和饮酒，但最近发现人乳头瘤病毒（HPV）与20%至25%的HNSCC（主要发生在口咽部）有病因学相关性。HPV通过表达两种病毒癌蛋白E6和E7引起人类癌症。这些癌蛋白通过泛素化降解两种主要的肿瘤抑制蛋白p53和pRb并使其不稳定。另外的研究表明，E6和E7可以直接结合p53和pRb以外的多种宿主蛋白（例如，巴克和p21（Cip 1）），进一步导致遗传不稳定性。然而，E6和E7单独表达不足以进行细胞转化，并且在病毒诱导的基因组不稳定性的情况下恶性进展所需的额外遗传改变是未知的。除了病因学差异外，HPV阳性癌症与HPV阴性癌症在治疗反应和生存结局方面在临床上不同，肿瘤HPV阳性是有利的预后生物标志物。进一步了解HPV阳性癌症的致癌作用和临床行为将改善HNSCC患者的疾病预防、患者护理和监测策略。(Clin Cancer Res 2009;15（22）：6758-62）
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with an annual incidence of approximately 400,000 worldwide. Although the principal risk factors for head and neck cancer remain tobacco and alcohol use, human papillomavirus (HPV) has recently been found to be etiologically associated with 20 to 25% of HNSCC, mostly in the oropharynx. HPV causes human cancers by expressing two viral oncoproteins, E6 and E7. These oncoproteins degrade and destabilize two major tumor suppressor proteins, p53 and pRb, through ubiquitination. Additional studies have shown that E6 and E7 can directly bind to multiple host proteins other than p53 and pRb (e.g., Bak and p21(Cip1)), further contributing to genetic instability. However, expression of E6 and E7 alone is not sufficient for cellular transformation, and the additional genetic alterations necessary for malignant progression in the setting of virus-induced genomic instability are unknown. In addition to the etiological differences, HPV-positive cancers are clinically distinct when compared with HPV-negative cancers with regard to treatment response and survival outcome, with tumor HPV-positivity being a favorable prognostic biomarker. Further understanding of carcinogenesis and clinical behavior of HPV-positive cancers will improve disease prevention, patient care, and surveillance strategies for HNSCC patients. (Clin Cancer Res 2009;15(22):6758-62)