Botswana-UPenn: Research Consortium of HPV-Related Cervical Cancer in HIV Patient

摘要： 低收入和中等收入国家的宫颈癌负担约占宫颈癌总负担的80%。 全球癌症发病率。在博茨瓦纳， 艾滋病毒呈阳性的妇女尚未得到认真研究。此外，还增加了 传染病和癌症，如最近的其他研究所见，包括默克尔细胞的存在 带有默克尔细胞多瘤病毒的癌。这表明这些代理人及其 对致癌过程的贡献。超过20%的人类癌症与 估计数字可能低于实际数字。的进步 包括从组织和其它材料中回收核酸的技术和方法， 大大提高了我们在相关癌症中检测和确认这些药物的能力。 项目#1中拟议研究的总体目标是确定传染性病原体的贡献 博茨瓦纳艾滋病毒阳性妇女宫颈癌的发展。这种急剧增加， 博茨瓦纳艾滋病毒阳性妇女的宫颈癌发病率可能由以下因素造成： 另外的药剂以及炎症反应，它们一起导致更快速和 增殖反应我们的项目将利用我们在博斯瓦纳独特的女性群体， 使我们能够监测从HPV和HIV阴性妇女到HPV感染妇女的宫颈植物群的变化。 宫颈癌是HIV和HPV阳性。我们的首要问题是找出更多的特工 这可能与该人群中宫颈癌的发生有关。我们的假设是 多种药物可导致艾滋病毒阳性妇女宫颈癌的发展， 博茨瓦纳，这可能导致炎症反应，协同导致宫颈癌。 癌我们将利用我们新开发的组合策略， 高通量测序技术。在查明这些代理人之后， 验证这些试剂在组织中的存在，感染细胞的转录分析以及 用相关试剂分析先天性和适应性炎症反应，并研究 对这些细胞的增殖作用。

Abstract: The cervical cancer burden in low and middle income countries make up about 80% of the total cervical cancer incidence worldwide. In Botswana the link between increased incidences of cervical cancer in HIV positive women has not been carefully explored. Furthermore there is an increased link between infectious disease and cancer as seen by additional recent studies including the presence of Merkel Cell Carcinomas with Merkel Cell Polyoma virus. This underscores the importance of these agents and their contributions to the oncogenic process. Greater than 20% of human cancers are associated with infectious agents and that estimate is likely to be lower than the actual number. The advances in technology and approaches which include recovery of nucleic acids from tissues and other materials has greatly improved our ability to detect and confirm the identifications of these agents in associated cancers. The overall goal of the proposed studies in project #1 is to determine the contributions of infectious agents to development of cervical carcinomas in HIV positive women in Botswana. This dramatic increase in cervical cancer incidence in HIV positive women in Botswana allows for the potential contributions of additional agents as well as the inflammatory response which together leads to a more rapid and proliferative response. Our project will take advantage of our unique cohorts of women in Bostwana that allows us to monitor changes in the cervical flora from HPV and HIV negative women to women with cervical cancer who are HIV and HPV positive. Our initial question will be to identify additional agents which may be linked to development of cervical carcinomas in this population. Our working hypothesis is that multiple agents can contribute to the development of cervical carcinomas in HIV positive women in Botswana and this can result in an inflammatory response which synergistically leads to cervical carcinomas. We will utilize our newly developed combinatorial strategy which bridges microarray technology with high throughput sequencing. The identification of these agents will be followed by validation of the presence of these agents in tissues, transcription analysis of infected cells as well as analysis of the innate and adaptive inflammatory responses with the associated agents, and investigating the proliferative effects on these cells.