HPV ETIOLOGY OF A SUBSET OF HEAD AND NECK CANCERS

部分头颈癌的 HPV 病因学

• 批准号: 6097443
• 负责人: KEERTI V SHAH
• 金额: $ 30.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6097443
• 关键词: Chlamydia trachomatis; Herpesviridae; alcoholism /alcohol abuse; antibacterial antibody; cancer risk; clinical research; comparative genomic hybridization; disease /disorder etiology; head /neck neoplasm; human papillomavirus; human subject; molecular oncology; neoplasm /cancer epidemiology; neoplastic process; oncoproteins; oral pharyngeal neoplasm; polymerase chain reaction; questionnaires; sex behavior; squamous cell carcinoma; tissue /cell culture; tobacco abuse; virus DNA; virus infection mechanism; virus related neoplasm /cancer

The objective of this proposal is to perform comprehensive virologic and focused epidemiologic and molecular pathogenesis studies to evaluate the hypothesis that a subset of head and neck squamous cell carcinomas (HNSCC-defined as SCC of the oral cavity, the pharynx and the larynx for this proposal) is etiologically linked to infections with human papillomaviruses (HPVs). In the USA, each year, there are about 41,000 cancer cases and about 12,00 deaths, due to HNSCC. Alcohol and tobacco use are the best recognized risk factors of HNSCC. Preliminary data suggest that, as compared to HPV-negative HNSCC, HPV- associated HNSCC (about 24 percent of all HNSCC) occur largely in the oropharynx and are less related to history of tobacco and alcohol use and to p53 mutations. The specific aims of the proposed studies are: (i) to define the site distribution of HPV- associated HNSCC, identify the HPV types involved and characterize the virus-cell relationships in HPV-positive tumors in terms of HPV copy numbers per cell, HPV transcripts, localization of the viral genome to tumor cell nuclei, viral integration into cellular DNA, and site of viral integration on the cellular chromosomes, and to compare cases at different sites for their serologic profiles against HPV-16 oncoproteins E6 and E7 and HPV-16 L1 protein; (ii) to describe the molecular and pathologic features of HPV-related tumor progression; and to (iii) to examine the clinical and epidemiologic correlates of HPV-associated HNSCC, especially with respect to survival and to exposure to risk factors relating to alcohol use, tobacco use and sexual activity. It is anticipate that about 1,300 cases of HNSCC attending clinics at Johns Hopkins will be investigated. If HPV etiology is established for a subset of HNSCC, patients with these tumors may benefit from HPV-specific immunotherapies which are being evaluated for the treatment of invasive cervical cancer.

本提案的目的是进行全面的病毒学和集中的流行病学和分子发病机制研究，以评估头颈鳞状细胞癌（HNSCC，本提案中定义为口腔、咽和喉部的鳞状细胞癌）的一个亚型的假设）在病因学上与人乳头瘤病毒（HPV）感染有关。 在美国，每年约有 41,000 例癌症病例，约 12,00 例因 HNSCC 死亡。 饮酒和吸烟是公认的 HNSCC 危险因素。 初步数据表明，与 HPV 阴性 HNSCC 相比，HPV 相关 HNSCC（约占所有 HNSCC 的 24%）主要发生在口咽部，与吸烟和饮酒史以及 p53 突变相关性较小。 拟议研究的具体目标是：(i) 定义 HPV 相关 HNSCC 的位点分布，确定涉及的 HPV 类型，并根据每个细胞的 HPV 拷贝数、HPV 来表征 HPV 阳性肿瘤中的病毒-细胞关系。转录本、病毒基因组在肿瘤细胞核中的定位、病毒整合到细胞 DNA 中以及病毒在细胞染色体上的整合位点，并比较不同位点的病例针对 HPV-16 癌蛋白 E6 和 E7 的血清学特征和 HPV-16 L1 蛋白； (ii) 描述 HPV 相关肿瘤进展的分子和病​​理特征； (iii) 检查 HPV 相关 HNSCC 的临床和流行病学相关性，特别是与生存以及暴露于与饮酒、吸烟和性活动相关的危险因素方面的相关性。 预计将对约翰·霍普金斯大学诊所就诊的约 1,300 例 HNSCC 病例进行调查。如果针对部分 HNSCC 确定了 HPV 病因，则患有这些肿瘤的患者可能会受益于 HPV 特异性免疫疗法，该疗法正在评估用于治疗浸润性宫颈癌。