HPV感染与头颈部鳞癌发病风险的病例对照研究

Along with smoking and alcohol use, exposure to human papillomavirus (HPV) has been established as an important risk factor for a subset of head and neck squamous cell carcinomas (HNSCC) in many foreign countries, but geographic differences and ethnic variations may cause significant differences. However, to date, no studies have sufficiently evaluated the association of HPV infection with risk of HNSCC in Chinese population. Therefore, we hypothesize that HPV infection may be the risk factor for HNSCC in Chinese population. To test this hypothesis, we will conduct a case-control study with 500 incident patients with HNSCC and 1000 cancer-free subjects as the normal controls to determine the magnitude of risk for HNSCC associated with HPV exposure. The cases and controls will be frequency-matched at a ratio of 1 to 2 by age, sex and tumor anatomic sites. HPV DNA will be detected in biopsy specimens by using polymerase chain reaction and fluorescence in situ hybridization, and HPV status in HPV-positive cases will be further confirmed by using p16 immunohistochemistry. In this study, we will determine whether HPV infection is associated with risk of HNSCC. We also will investigate whether smoking and alcohol drinking modify or confound the association between HPV exposure and risk of HNSCC. It is our speculation that 1) there is a significant association between HPV infection and risk of HNSCC in Chinese population; 2) we will be the first to obtain information on prevalence and types of HPV infection in HNSCC patients and normal controls in Chinese population; and 3) the results from this study will provide clinicians with novel information for early detection, diagnosis and treatment as well as primary cancer prevention based on clinical and pathological features between HPV-positive and HPV-negative HNSCC patients.

国外研究表明， HPV感染可能与一部分头颈部鳞癌的发生相关，而且这种相关性可能存在区域差异或种族特异性，但目前尚无针对我国人群的相关性研究。我们推测HPV感染也可能是我国部分头颈部鳞癌发生的危险因素。本研究计划以头颈部鳞癌和非癌患者为研究对象，采用病例对照研究设计，拟纳入头颈部鳞癌病例组500例及非癌对照组1000例，并根据年龄、性别及发病部位进行1:2匹配。应用PCR、反向杂交及原位杂交技术检测组织样本中的HPV DNA，同时应用免疫组化方法检测组织中p16蛋白的表达。因为烟草和酒精是头颈部鳞癌发病的主要危险因素，故应注意分析吸烟和饮酒在HPV感染与头颈部鳞癌关系中的混杂或交互作用。预期可获得：①我国HPV感染与头颈部鳞癌发病风险的相关性；②头颈部鳞癌和非癌对照组中HPV的感染率和型别分布；③总结存在HPV感染的头颈部鳞癌患者的临床病理特征，为相关肿瘤的诊治和预防提供一定依据。

研究背景：. 头颈部肿瘤发病率排全身癌症第六位。近期研究表明一部分头颈部鳞癌的发生可能与HPV感染有关，而且这种相关性可能存在区域差异或种族特异性，但目前尚无针对我国人群的相关性研究。我们推测HPV感染也可能是我国部分头颈部鳞癌发生的危险因素。.主要研究内容：. 本研究课题采用大样本的分子流行病学研究设计，以头颈部鳞癌和非癌患者作为病例对照研究对象，以肿瘤组织标本作为研究样本，检测标本中HPV感染率和型别特点、HPV16病毒载量和病毒整合状态，同时应用免疫组化方法检测组织中p16蛋白的表达。.重要结果：. 本项病例对照研究的结果提示HPV感染与头颈部鳞癌（喉癌、口咽癌）发生呈显著性相关。而且HPV16的致癌作用在不吸烟、不饮酒的患者中更显著。病例组与对照组阳性的肿瘤标本的HPV病毒载量无明显统计学差异；但病例组中HPV16多以整合或混合状态存在，而对照组则多为游离状态存在。这些结果提示HPV16前期感染可能在一部分患者中起到致癌作用。.科学意义：. 头颈部鳞癌患者中HPV感染率高于对照组。HPV16为头颈部鳞癌患者中最常见的感染型别。HPV感染与头颈部鳞癌的发生独立相关，特别是在非吸烟、非饮酒患者中。本研究是目前中国人群当中最大的探索HPV感染与头颈部鳞癌发生相关性的病例对照研究。