HPV AND CERVIX NEOPLASIA--A CASE CONTROL STUDY

HPV 和子宫颈肿瘤——病例对照研究

• 批准号: 6152842
• 负责人: HANS-OLOV ADAMI
• 金额: $ 15.1万
• 依托单位: KAROLINSKA INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6152842
• 关键词: MHC class II antigen; Scandinavian country; biopsy; cancer registry /resource; cancer risk; cellular immunity; cervical /vaginal smear; cervix neoplasms; clinical research; female; genetic strain; human papillomavirus; human subject; longitudinal human study; neoplasm /cancer epidemiology; nucleic acid sequence; pathologic process; smoking; viral carcinogenesis; virus genetics; virus infection mechanism; virus morphology; virus related neoplasm /cancer; women's health; MHC class II antigen; Scandinavian country; biopsy; cancer registry /resource; cancer risk; cellular immunity; cervical /vaginal smear; cervix neoplasms; clinical research; female; genetic strain; human papillomavirus; human subject; longitudinal human study; neoplasm /cancer epidemiology; nucleic acid sequence; pathologic process; smoking; viral carcinogenesis; virus genetics; virus infection mechanism; virus morphology; virus related neoplasm /cancer; women's health

DESCRIPTION: (Adpated from the Applicant's Abstract): The applicants' objective is to advance the understanding of the role played by genital human papillomavirus (HPV) in the etiology of carcinoma in situ (CIS) -- and inferentially invasive cancer -- of the cervix. While a causal role of HPV is likely, no large population-based, prospective study has examined its role in the natural history from normal epithelium to CIS, nor the role of cell-mediated immunity (as determined by HLA haplotype), microheterogeneity (or mutations) in the HPV genome, or of other factors that may determine transience/persistence of HPV infection. Nor has the purported orderly progression or monoclonal origin of cervix neoplasia been established. They propose a broad, interdisciplinary case-control study, nested in a population-based cohort. This study uses unique Swedish opportunities for a stringent study base definition, long-term follow-up and retrieval of smears and histopathologic specimens; it has an extensive morphologic and molecular component. The main specific questions relate to 1) determinants of progression: long-term pattern of infection (transience, persistence, reinfection) by HPV type, concordance between HPV in smears and CIS lesions, microheterogeneity or acquired mutations in the HPV genome, effect modification by HLA haplotype and/or smoking; 2) progression and clonality: correlation between HPV and the morphology as well as mono- or polyclonality of concomitant lesions as indicated by x-chromosome inactivation. They will follow up through 1993 a population-based cohort of women whose first PAP smear after 1969 was normal. At least 400 incident cases of CIS and 400 matched controls will be included and subjected to a telephone interview. On average five sequential smears from each subject (a total of about 4,000 smears) will undergo DNA extraction and PCR-based analyses including typing of 19 HPV-types, and of HLA class II haplotypes (HLA-DQB1 and HLA-DRB1) in one smear per individual. Also, in a selected set (about 100 cases) sequencing of a proportion of the HPV genome will be performed to study microheterogeneity. Detailed studies of progression and clonality will be carried out; the specimens from about 50 cases of CIS with multiple discrete lesions will be microdissected, followed by DNA extraction and analysis of HPV as well as X-chromosome inactivation. These data will be used on a number of different analyses including conditional logistic regression.

描述：（根据申请人的摘要进行拟合）：申请人的 目的是提高对生殖器作用的理解 人乳头瘤病毒（HPV）在原位癌病因（CIS）和 宫颈的推断侵入性癌。 而HPV的因果角色 很可能没有大型基于人群的前瞻性研究检查了其 从正常上皮到顺式的自然历史中的作用，也没有 细胞介导的免疫力（如HLA单倍型确定），微异质性 （或突变）在HPV基因组或其他可能决定的因素中 HPV感染的瞬时/持久性。 据称没有有序的 建立了子宫颈肿瘤的进展或单克隆起源。 他们 提出了一项广泛的跨学科案例对照研究，该研究嵌套在 基于人群的队列。 这项研究使用了独特的瑞典机会 严格的研究基础定义，长期随访和检索涂片 和组织病理标本；它具有广泛的形态和分子 成分。 主要问题与1）进展的决定因素有关： HPV的长期感染模式（瞬态，持久性，再感染） 类型，涂片和顺式病变中的HPV之间的一致性，微分类性 或在HPV基因组中获得的突变，HLA的效果修饰 单倍型和/或吸烟； 2）进展和克隆性： HPV和形态以及伴随的单或多克隆性 X染色体灭活所表明的病变。 他们将跟进至1993年，以人群为基础的妇女队列 1969年以后的第一个子宫颈抹片是正常的。 至少400例独联体 将包括400个匹配的控件并进行电话 面试。 平均每个受试者的五个顺序涂片（总共 大约4,000张涂片）将接受DNA提取和基于PCR的分析 包括键入19 HPV型和HLA II类单倍型（HLA-DQB1） 和HLA-DRB1）每个人的涂片。 另外，在选定的集合中（关于 100例）将进行一定比例的HPV基因组的测序 研究微观分子。 详细的进展和克隆性研究 将进行；来自大约50例CI的标本，有多个 离散病变将被微解释，然后进行DNA提取，然后 HPV和X染色体灭活的分析。 这些数据将是 用于许多不同的分析，包括条件逻辑 回归。