HPV: Biology, Clinical Significance and Epidemiology

我们建议继续多学科研究人乳头瘤病毒（HPV）在肛门生殖器癌病因学中的作用。该计划将流行病学和分子生物学方法纳入三个项目，并提供病毒学、病理学、生物统计学和行政支持四个核心功能的支持。这项工作的核心是一系列病例对照研究，调查宫颈癌鳞状细胞癌、肛门癌、外阴癌、阴道癌、宫颈腺癌和阴茎癌的风险因素。这些研究人员的研究结果将增加这个项目过去十三年发展起来的数据库。用于鉴定HPV DNA的已建立的聚合酶链反应程序以及在本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。一个新的焦点发生在生殖区域的多种癌症被引入，目标是建立原发和/或继发状态的肿瘤随后的初步诊断。一组至少有一种其他原发性器官癌的妇女将与适当的对照者一起重新接受访谈，了解可能导致第二种原发肿瘤风险的暴露。将获取组织和血液样本进行病毒序列、血清学和基因检测。将确定病毒整合位点的独特性和病毒变异对疾病过程的贡献。HLA基因型在HPV引发的癌症易感性中的作用的研究将会进一步扩大。比较基因组杂交将继续用于鉴定染色体区域的缺失或增加，微阵列方法将用于研究异常基因表达，特别关注染色体3、5和20的基因定位。

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.