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

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：（改编自申请人摘要）：申请人的 目的是增进对生殖器所发挥作用的理解 人乳头瘤病毒 (HPV) 在原位癌 (CIS) 病因学中的作用——以及 推断性侵袭性癌症——子宫颈癌。 虽然 HPV 具有因果作用 很可能，没有大规模的基于人群的前瞻性研究检验了其 从正常上皮到 CIS 的自然史中的作用，也没有 细胞介导的免疫（由 HLA 单倍型确定）、微观异质性 HPV 基因组（或突变），或其他可能决定的因素 HPV 感染的短暂性/持续性。 也没有所谓的有序 宫颈肿瘤的进展或单克隆起源已确定。 他们 提出一项广泛的、跨学科的病例对照研究，嵌套在 基于人群的队列。 这项研究利用瑞典独特的机会 严格的研究基础定义、长期随访和涂片检索 和组织病理学标本；它具有广泛的形态和分子 成分。 主要的具体问题涉及 1) 进展的决定因素： HPV 感染的长期模式（短暂性、持续性、再感染） 类型、涂片中 HPV 与 CIS 病变之间的一致性、微观异质性 或 HPV 基因组获得性突变，通过 HLA 进行修饰 单倍型和/或吸烟； 2）进展和克隆性：之间的相关性 HPV 和伴随病毒的形态以及单克隆或多克隆 X 染色体失活表明病变。 他们将在 1993 年对一个以人口为基础的妇女群体进行跟踪调查，她们的 1969 年之后第一次子宫颈抹片检查结果正常。 至少 400 起 CIS 事件 并且将包括 400 个匹配的控件，并通过电话进行控制 面试。 每个受试者平均进行五次连续涂片（总共 约 4,000 个涂片）将进行 DNA 提取和基于 PCR 的分析 包括 19 种 HPV 类型和 HLA II 类单倍型 (HLA-DQB1 和 HLA-DRB1) 每人一次涂片。 此外，在选定的集合中（大约 100个病例）将对HPV基因组的一部分进行测序，以 研究微观异质性。 进展和克隆性的详细研究 将进行；标本取自约 50 例 CIS 病例， 离散病灶将被显微解剖，然后提取 DNA HPV 以及 X 染色体失活分析。 这些数据将 用于许多不同的分析，包括条件逻辑分析 回归。

项目成果

HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients.

• DOI: 10.1054/bjoc.2000.1619
• 发表时间: 2001-03-23
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Hu X;Pang T;Guo Z;Mazurenko N;Kisseljov F;Pontén J;Nistér M
• 通讯作者: Nistér M

Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden.

• DOI: 10.1158/0008-5472.can-15-1788
• 发表时间: 2016-02-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Lu D;Sundström K;Sparén P;Fall K;Sjölander A;Dillner J;Helm NY;Adami HO;Valdimarsdóttir U;Fang F
• 通讯作者: Fang F