HPV Type Distribution and Biomarkers of Cervical Neoplasia Progression in Africa

这项建议建立在我们目前的出口中心资助的研究的基础上， 女性高危型人乳头瘤病毒持续感染分子生物学基础 大学生虽然HR-HPV感染是宫颈癌的主要原因，但大多数HPV感染在一段时间内是明确的。 大约几个月，只有持续感染HR-HPV的女性才真正有患癌症的风险。如果 HPV持续性的“生物标志物”可以在第一次就诊时确定，然后可以指导仔细的后续护理。 给那些真正需要它的女性，以一种具有成本效益和效率的方式。此外，还有相当多的 欧洲裔美国人（EA）和非洲人之间宫颈癌发病率和死亡率的差异 美国（AA）全国女性。具体来说，在南卡罗来纳州，AA女性的1.6倍更有可能是 被诊断为宫颈癌，比EA女性死亡的可能性高2.5倍。虽然其中大部分 差异被归因于获得护理的差异，我们现在有证据表明，生物和 分子机制也可能起作用。在目前的出口融资期间，我们启动了 卡罗莱纳妇女护理研究（CWCS），其中新生巴氏试验材料中的HPV状态和类型 就读于南卡罗来纳州大学或克拉夫林大学的女大学生 在他们的大学生活期间，每六个月确定一次。我们还进行了宫颈细胞学检查 (from巴氏试验），确定宫颈粘液中的细胞因子谱，并在每个时间点进行问卷调查。 访问，收集有关生活方式因素，压力，吸烟，歧视，饮食和身体的信息， 活动此外，在第一次就诊期间收集血液用于DNA分离和单个DNA的表征。 细胞因子基因（IL-6、TNF-α、RANTES和 GM-CSF），可能参与HPV持续性。还收集第二次巴氏试验用于RNA分离。 来自CWCS的初步结果表明，AA妇女的HR-HPV类型分布与 EA妇女; AA妇女清除某些HR-HPV类型比EA妇女慢; AA妇女 比EA女性更容易发生高级病变。任何潜在有用的生物标志物 需要在脱落细胞中可检测到进展，以便在临床上可用于分类， 宫颈癌的早期症状有哪些因此，在我们之前的EXPORT融资期间，我们完善了 从巴氏试验材料中提取和纯化高质量RNA的技术，适用于微阵列，和 我们对这些样本中基因表达的初步研究证明了进行基因表达的可行性 使用来自宫颈脱落细胞的RNA的表达谱研究。

This proposal builds upon and expands studies funded under our current EXPORT Center, which investigate the molecular and biologic basis of persistent high risk human papillomavirus (HR-HPV) infection in female college students. While HR-HPV infection is the major cause of cervical cancer, most HPV infections clear in a matter of months, and only women who have persistent HR-HPV infection are truly at risk for cancer. If "biomarkers" of HPV persistence can be identified at a first visit, then careful follow-up care could be directed to those women that really need it, in a cost effective and efficient fashion. Furthermore, there is considerable disparity in cervical cancer incidence and mortality rates between European American (EA) and African American (AA) women nationwide. Specifically, in South Carolina, AA women are 1.6-fold more likely to be diagnosed with cervical cancer, and 2.5 times more likely to die of it than EA women. While much of this disparity has been attributed to differences in access to care, we now have evidence that biological and molecular mechanisms may also play a role. During the current EXPORT funding period we initiated the Carolina Women's Care Study (CWCS) in which the HPV status and type in Pap test material from freshman female college students attending either the University of South Carolina (USC) or Claflin University (CU) was determined every six months for the duration of their college experience. We also followed cervical cytology (from Pap tests), determined the cytokine profiles in cervical mucus, and administered questionnaires at each visit that collected information concerning lifestyle factors, stress, smoking, discrimination, diet, and physical activity. In addition, blood was collected during the first visit for DNA isolation and characterization of single nucleotide polymorphisms (SNPs) in the promoter region of cytokine genes (IL-6, TNF-alpha, RANTES, and GM-CSF) that may be involved in HPV persistence. A second Pap test was also collected for RNA isolation. Initial results from the CWCS indicate that AA women have a different HR-HPV type distribution than EA women; that AA women clear certain HR-HPV types slower than EA women; and that AA women are more likely to develop high grade lesions than EA women. Any potential useful biomarker of progression would need to be detectable in exfoliated cells, in order to be clinically useful in the triage of women at risk for cervical cancer. Therefore, during our previous EXPORT funding period we perfected techniques for extracting and purifying high quality RNA, suitable for microarrays, from Pap test material, and our preliminary studies of gene expression in these samples demonstrated the feasibility of conducting gene expression profiling studies using RNA from cervical exfoliated cells.