HPV Type Distribution and Biomarkers of Cervical Neoplasia Progression in Africa

这项建议建立在我们目前出口中心资助的研究的基础上，并扩展了这些研究，这些研究调查 女性持续高危人乳头瘤病毒感染的分子生物学基础 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 只有几个月的时间，只有持续感染HR-HPV的女性才有真正的癌症风险。如果 HPV持久性的“生物标志物”可以在第一次就诊时被识别出来，然后可以指导仔细的后续护理 对于那些真正需要它的女性，以一种成本效益和效率的方式。此外，还有相当多的 欧美和非洲宫颈癌发病率和死亡率的差异 美国(AA)全国妇女。具体地说，在南卡罗来纳州，AA女性患癌症的可能性是男性的1.6倍 被诊断为宫颈癌，死于宫颈癌的可能性是EA女性的2.5倍。虽然这其中的大部分 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 分子机制也可能起到一定作用。在当前的出口融资期间，我们发起了 卡罗莱纳州妇女关爱研究(CWCS)一年级学生巴氏试验材料中HPV的状况和类型 南卡罗来纳大学(USC)或克拉夫林大学(CU)的女大学生 每六个月确定一次，用于他们的大学经历。我们还进行了宫颈细胞学检查。 (从巴氏试验中)，测定宫颈粘液中的细胞因子谱，并在每个 访问收集的有关生活方式因素、压力、吸烟、歧视、饮食和身体状况的信息 活动。此外，在第一次访问期间采集血液进行DNA分离和单个 细胞因子基因启动子区域(IL-6、TNF-α、RANTES和 GM-CSF)，可能与HPV持续存在有关。第二次Pap试验也被收集用于RNA分离。 CWCS的初步结果表明，再障女性的HR-HPV类型分布不同于 EA女性；AA女性清除某些HR-HPV类型比EA女性慢；AA女性 比电针女性更有可能发展为高级别皮损。任何潜在的有用的生物标志物 需要在脱落的细胞中检测到进展，才能在临床上用于对 有患宫颈癌风险的妇女。因此，在我们之前的出口融资期间，我们完善了 从巴氏试验材料中提取和纯化适合于微阵列的高质量RNA的技术，以及 我们对这些样本中基因表达的初步研究证明了进行基因转移的可行性 使用宫颈脱落细胞的RNA进行的表达谱研究。

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.