Molecular Epidemiology of Persistent HPV Infection

描述(由申请人提供)：这项竞争性续期赠款是CA70269第二次也是最后一次续期申请，CA70269最初的资金用于对巴西圣保罗低收入女性人群中人乳头瘤病毒(HPV)感染和宫颈肿瘤的自然历史进行流行病学研究。在与巴西同事的合作下，三名作者于1993年开始了这项研究，试图了解HPV自然历史的属性，这些属性可能有助于设计预防宫颈癌的策略。考虑到宫颈癌对公众健康和经济的重要性，以及人们对HPV疫苗和在癌症筛查中使用HPV的广泛兴趣，有必要对HPV的自然历史进行长期的多学科研究。 截至1997年3月，这项研究收集了2529名女性受试者。受试者在第一年每4个月跟踪一次预定的回报，此后每年跟踪两次，总共持续5年。参与者接受基于问卷的访谈，采集宫颈样本进行巴氏细胞学和HPV检测，并抽取血液样本进行HPV抗体血清学检测。后续行动将在2002年8月队列研究的现有资金结束时完成。 这项研究的最初目标(1996-1999年资助期)是：(1)研究无症状妇女持续HPV感染的患病率和发病率；(2)验证持续感染HPV会增加宫颈病变风险的假设；(3)寻找持续感染宫颈HPV的决定因素；(4)寻找可能导致宫颈病变风险增加的HPV分子变异；(5)验证宫颈病毒负担可能与持续感染和病变风险相关的假设；以及(6)研究对HPV的抗体应答作为持续HPV感染和病变风险的预测因子。在上一次成功的延续中(1999-02资助期)，这些目标被扩大到包括：(7)寻找与HPV持续存在和病变严重程度相关的特定的人类白细胞抗原单倍型，以及(8)测试P53基因多态可能影响对病毒持续抵抗和病变发展的假设。这一竞争的继续是对研究期间积累的数据库进行深入的统计分析，并增加一个新的目标：(9)研究胰岛素生长因子在调节持续性HPV感染和宫颈病变风险中的作用。

DESCRIPTION (provided by applicant): This competing continuation grant is the second and last request for renewal of CA70269, the original funding for an epidemiologic study of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a low-income female population in Sao Paulo, Brazil. In collaboration with Brazilian colleagues, three of the authors began the study in 1993 in an attempt to understand attributes of the natural history of HPV that could be instrumental in designing strategies for preventing cervical cancer. Considering the public health and economic importance of cervical cancer and the widespread interest in HPV vaccines and in using HPV in cancer screening there is a need for long-ranging multidisciplinary studies of the natural history of HPV. The study accrued 2529 female subjects through March 1997. Subjects have been followed up in scheduled returns every 4 months in the first year, and twice yearly thereafter for a total of 5 years. Participants undergo a questionnaire-based interview have a cervical specimen taken for Pap cytology and HPV testing, and a blood sample drawn for HPV antibody serology. Follow-up will have been completed at the time current funding for the cohort study finishes in August 2002. The study's original objectives (1996-99 funding period) were: (1) to study the prevalence and incidence of persistent HPV infection in asymptomatic women; (2) to verify the hypothesis that persistent HPV infection increases risk of cervical lesions; (3) to search for determinants of persistent cervical HPV infection; (4) to search for molecular variants of HPV that may lead to an increased risk of cervical lesions; (5) to verify the hypothesis that viral burden in the cervix may be correlated with persistent infections and with lesion risk; and (6) to study the antibody response to HPV as a predictor of persistent HPV infection and of lesion risk. In the last successful continuation (1999-02 funding period) these objectives were expanded to include: (7) the search for specific HLA haplotypes associated with HPV persistence and lesion severity, and (8) to test the hypothesis that p53 gene polymorphism may influence resistance against viral persistence and to lesion development. This competing continuation is to conduct in-depth statistical analyses of the database accrued during the study and to add a new objective: (9) to study the role of insulin growth factors in mediating risk of persistent HPV infection and cervical lesions.