MOLECULAR EPIDEMIOLOGY OF PERSISTENT HPV INFECTION

持续性 HPV 感染的分子流行病学

• 批准号: 2769851
• 负责人: EDUARDO L. FRANCO
• 金额: $ 20.96万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-11 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769851
• 关键词: blood chemistry; cancer risk; capsid; cervical /vaginal smear; cervix neoplasms; clinical research; enzyme linked immunosorbent assay; female; female reproductive system disorder diagnosis; genetic strain; human papillomavirus; human subject; humoral immunity; latent virus infection; longitudinal human study; molecular oncology; neoplasm /cancer epidemiology; neoplastic process; oncogenic virus; polymerase chain reaction; questionnaires; serology /serodiagnosis; statistics /biometry; virus antigen; virus related neoplasm /cancer; women's health

DESCRIPTION: (Adapted from Investigator's Abstract) In 1993 the authors began an epidemiologic cohort study of the natural history of human Papillomavirus (HPV) infection and cervical neoplasia in a population of low income women in Sao Paulo, Brazil, one of the highest risk areas worldwide for cervical cancer. This study was designed to answer questions that have not yet been addressed in epidemiologic investigations of this neoplastic disease. Although few would dispute that HPV infection is an important cause of cervical cancer, most of the epidemiologic data have come from retrospective studies, which do not provide information on the dynamics of cervical HPV infection in the same individual. The Brazilian cohort study is testing the hypothesis that persistent infections with oncogenic HPV types are more likely to be the true precursor events leading to cervical carcinogenesis. Persistence of infections is being documented on the basis of molecular variants of HPV, which provides a much finer level of detail than simple HPV typing and may unveil in addition to persistence per se other prognostic markers of progression across the spectrum of cervical lesions. The study will accrue 2000 female subjects through February 1996. Subjects are being followed up over a 5 year period in scheduled returns every 4 months, in the first year, and once yearly thereafter, for a total of 8 visits as follows: initial, 4, 8, 12, 24, 36, 48, and 60 months. In each of these visits, subjects are submitted to a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and a blood sample drawn for serologic testing for HPV antibodies. A cervicography is performed once in the first year and at 24 and 48 months. Considering the public health and economic importance of cervical cancer screening and given the current impetus within the federal government to examine the utility of HPV testing in augmenting existing screening programs, the investigators argue that there is a clear need for long-ranging multidisciplinary studies of the natural history of this malignant disease. In brief, this ongoing investigation will further understanding of the etiopathogenesis of cervical neoplasia by tackling the following specific objectives: (1) to study the prevalence and incidence of transient and persistent cervical HPV infection in asymptomatic women; (2) to verify the hypothesis that persistent HPV infection increases risk of low grade and high grade cervical lesions; (3) to search for epidemiologic determinants of persistent cervical HPV infection; (4) to search for specific molecular variants of oncogenic types of HPV that may be associated with an increased risk of cervical neoplasia; (5) to verify the hypothesis that measures of viral burden in the cervix may be correlated with persistent infections and with low and high grade lesions; and (6) to study the humoral immune response to capsid antigens of HPV as a possible marker of persistence of cervical HPV infection and of likelihood of progression in lesion severity.

描述：（改编自研究者摘要）1993年，作者 开始了一项关于人类自然史的流行病学队列研究， 宫颈癌高危人群中HPV感染与宫颈癌的关系 巴西圣保罗是世界上风险最高的地区之一， 宫颈癌的治疗方法 这项研究旨在回答那些 尚未在这种肿瘤的流行病学调查中得到解决 疾病 虽然很少有人会质疑HPV感染是一个重要的 宫颈癌的病因，大部分流行病学数据来自 回顾性研究，没有提供关于 宫颈HPV感染在同一个人。 巴西队列研究 正在验证致癌HPV持续感染的假设， 类型更有可能是导致宫颈癌的真正前兆事件 致癌作用 感染的持续性是根据 HPV的分子变异，它提供了一个更精细的细节水平， 而不是简单的HPV分型， 其他宫颈癌进展的预后标志物 病变 该研究将在1996年2月之前招募2000名女性受试者。 科目 在5年期间，每4年定期返回一次， 第一年一个月，以后每年一次，共8个月。 访视如下：初始、4、8、12、24、36、48和60个月。 在每个 在这些访问中，受试者被提交给基于问卷的访谈， 有一个子宫颈标本采取巴氏细胞学和HPV检测，和血液 抽取样本进行HPV抗体血清学检测。 宫颈造影术是 在第一年以及24个月和48个月时进行一次。 考虑到宫颈癌的公共卫生和经济重要性， 筛选，并考虑到目前联邦政府内部的动力， 检查HPV检测在增强现有筛查中的效用 研究人员认为，有一个明确的需要， 长期的多学科研究的自然历史， 恶性疾病 简而言之，正在进行的调查将进一步 透过处理子宫颈癌的发病机制， 具体目标如下：（1）研究 无症状妇女中的一过性和持续性宫颈HPV感染;（2） 为了验证持续性HPV感染会增加低风险的假设， 分级和高分级宫颈病变;（3）寻找流行病学 持续性宫颈HPV感染的决定因素;（4）寻找 可能与HPV致癌类型相关的特定分子变异体 与宫颈肿瘤的风险增加;（5）验证假设 子宫颈中病毒负荷的测量可能与 持续性感染和低度和高度病变;和（6）研究 对HPV衣壳抗原的体液免疫应答作为一种可能的标志物 宫颈HPV感染的持续性和进展的可能性 病变严重程度。