HPV: Biology, Clinical Significance and Epidemiology

HPV：生物学、临床意义和流行病学

• 批准号: 6512384
• 负责人: JAMES K. MCDOUGALL
• 金额: $ 190.12万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-10 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6512384
• 关键词: human papillomavirus; multiple primary neoplasia; neoplasm /cancer epidemiology; neoplastic process; reproductive system neoplasm; viral carcinogenesis

We propose to continue multi-disciplinary studies of the role of human papillomaviruses (HPV) in the etiology of anogenital cancers. The program incorporates epidemiologic and molecular biology approaches in the three projects, with support form four core functions including virology, pathology, biostatistics and administrative support. The nucleus of this effort is a series of case-control studies investigating the risk factor involved in squamous cell cervical cancer, anal cancer, vulvar cancer, vaginal cancer, adenocarcinoma of the cervix and penile cancers. The results from these studiers will increase the data base developed over the past thirteen years of this Program Project. Established polymerase chain reaction procedures for identification of HPV DNA together with the serologic tests developed in this program will continue to be used to establish virus infection and evidence of immune responses. A new focus on the occurrence of multiple cancers of the genital area is introduced, with the goal of establishing the primary and/or secondary state of tumors subsequent to an initial diagnosis. A group of women who have developed at least one additional primary anogenital cancer will be re- interviewed, together with appropriate controls, about exposures that may have contributed to the risk of a second primary tumor. Tissue and blood samples will be acquired for virus sequence, serologic and genetic testing. Determinations will be made of the uniqueness of the viral integration sites and the contribution of virus variants to the disease process. Studies of the roles of HLA genotypes in susceptibility to HPV- initiated cancer will be expanded. Comparative genome hybridization will continue to be used to id4entify loss or gain of chromosome regions and microarray methods used to investigate abnormal genes expression, with a particular focus of genes mapping on chromosomes 3, 5, and 20.

我们建议继续对人类乳头瘤病毒(HPV)在肛门生殖道癌病因中的作用进行多学科研究。该计划在三个项目中结合了流行病学和分子生物学方法，并由病毒学、病理学、生物统计学和行政支持等四个核心职能提供支持。这项工作的核心是一系列病例对照研究，调查鳞状细胞宫颈癌、肛门癌、外阴癌、阴道癌、宫颈癌和阴茎癌的风险因素。这些研究人员的研究结果将增加该计划项目过去13年中开发的数据库。已建立的用于鉴定HPV DNA的聚合酶链式反应程序以及在该计划中开发的血清学测试将继续用于确定病毒感染和免疫反应的证据。对生殖器区域多发性癌症的发生进行了新的关注，目的是在初步诊断后确定肿瘤的原发和/或继发状态。一组至少额外患上一种原发肛门生殖器癌的女性将与适当的对照组一起，就可能导致第二种原发肿瘤风险的暴露进行重新访谈。将采集组织和血液样本进行病毒序列、血清学和基因测试。将确定病毒整合部位的独特性以及病毒变异在疾病过程中的作用。人类白细胞抗原基因型别在人类乳头状瘤病毒引发的癌症易感性中的作用的研究将会扩大。将继续使用比较基因组杂交来识别染色体区域的丢失或获得，并使用微阵列方法来研究异常基因的表达，特别是定位在第3、5和20号染色体上的基因。