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子宫颈癌负担约占子宫颈癌总负担的80%。 全球癌症发病率。在博茨瓦纳，#年宫颈癌发病率增加之间的联系 艾滋病毒阳性妇女还没有得到仔细的研究。此外，两者之间的联系也在增加 最近的其他研究，包括默克尔细胞的存在，发现了传染病和癌症 默克尔细胞多瘤病毒致癌。这突显了这些代理人和他们的 对致癌过程的贡献。超过20%的人类癌症与 这一估计很可能低于实际数字。新技术的进展 包括从组织和其他材料中回收核酸的技术和方法已经 极大地提高了我们在相关癌症中检测和确认这些病原体的能力。 项目1中拟议研究的总体目标是确定感染性病原体的作用。 与博茨瓦纳艾滋病毒阳性妇女宫颈癌的发生有关。这种戏剧性的增长 博茨瓦纳艾滋病毒阳性妇女的宫颈癌发病率允许潜在的 其他制剂以及炎症反应共同导致更迅速和 增殖反应。我们的项目将利用我们在Bostwana的独特女性队列 使我们能够监测从HPV和HIV阴性的妇女到患有HPV和HIV的妇女宫颈菌群的变化 HIV和HPV阳性的宫颈癌患者。我们最初的问题将是确定更多的代理 这可能与这一人群中宫颈癌的发生有关。我们的工作假设是 多种因素可能导致艾滋病毒阳性妇女宫颈癌的发生 博茨瓦纳，这会导致炎症反应，协同作用导致宫颈 癌症。我们将利用我们最新开发的组合策略来桥接微阵列 高通量测序技术。在确定这些代理之后，将 确认这些病原体在组织中的存在，感染细胞的转录分析以及 与相关因素相关的先天和获得性炎症反应的分析和调查 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.