HPV: Biology, Clinical Significance and Epidemiology

我们建议继续多学科研究的作用，人乳头瘤病毒（HPV）的病因学肛门生殖器癌。该计划在三个项目中采用流行病学和分子生物学方法，并得到四个核心功能的支持，包括病毒学，病理学，生物统计学和行政支持。这项工作的核心是进行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、宫颈腺癌和阴茎癌的危险因素。这些研究人员的成果将增加本计划项目过去13年来开发的数据库。已建立的用于鉴定HPV DNA的聚合酶链反应程序以及本项目中开发的血清学检测将继续用于确定病毒感染和免疫应答的证据。介绍了一个新的重点对生殖器区域的多个癌症的发生，与建立的主要和/或继发状态的肿瘤后，初步诊断的目标。将对一组已发生至少一种其他原发性肛门生殖器癌的妇女与适当的对照组一起重新进行访谈，了解可能导致第二种原发性肿瘤风险的暴露情况。将采集组织和血液样本进行病毒测序、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体对疾病过程的贡献。HLA基因型在HPV引发的癌症易感性中的作用的研究将得到扩展。比较基因组杂交将继续被用于鉴定染色体区域的丢失或获得，微阵列方法用于研究异常基因表达，特别关注染色体3、5和20上的基因定位。

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.