MOLECULAR EPIDEMIOLOGY OF HUMAN PAPILLOMAVIRUS IN IMMUNOSUPPRESSED WOMEN

人乳头瘤病毒(HPV)感染是最常见的性行为之一 传播疾病，感染大约四分之一的性行为 经验丰富的人群。至少有100种不同的HPV类型， 某些高危类型与生殖器肿瘤有关。 了解生殖器HPV导致恶性肿瘤的过程 由于缺乏现成的文化方法论， 很大比例的潜伏和亚临床感染，以及长期的 从早期感染到生殖器肿瘤发展之间的时间。 大量数据表明，生殖器HPV的临床表达， 包括生殖器肿瘤，在免疫功能减退中发生得更快 宿主，而这群患者可能是理想的人群， 研究人乳头瘤病毒感染的自然病史。此外，实心器官 移植群体可能是最适合研究的群体，因为 他们的免疫抑制具有突发性和可预测性。因此， 该项目将建立3个感染HPV的妇女队列，包括 肾移植受者，患有终末期肾病的妇女，以及艾滋病毒- 受感染的妇女将每隔4个月进行前瞻性跟踪 常规妇科检查和阴道镜检查，宫颈阴道灌洗 对于HPV-PCR，生殖器共病原体培养和宫颈活检 已注明。每年将对大约240名女性进行评估，HPV呈阳性 女性将被前瞻性地跟踪调查。这个项目的主要焦点是 为了确定HPV基因表达、DNA复制、 利用创新的分子生产病毒粒子和整合病毒 RT-PCR和原位杂交等技术，并将其与 这些数据与3个队列中的临床和组织病理学结果相一致。 病毒表达的变化将根据潜在的 疾病、免疫抑制程度和HPV类型。我们假设 免疫受损者HPV早期基因表达上调 这些分子事件将与临床和 /或病理性疾病进展。这个项目代表着一个 包括临床传染病在内的多学科努力， 妇科/肿瘤学、流行病学和分子病毒学 对实现这些目标至关重要。从一份报告中获得的信息 对这些数据的详细分析可以提供重要的新见解 疾病进展的早期标志，不仅适用于 大量免疫功能低下的人群，但对免疫能力强的患者来说 井。

Human papillomavirus (HPV) infections are among the most common sexually transmitted diseases, infecting perhaps one-quarter of the sexually experienced population. There are at least 100 different HPV types, and certain high-risk types are associated with genital neoplasia. Understanding the process by which genital HPV leads to malignancy has been hampered by the absence of readily available culture methodology, a large percentage of latent and subclinical infections, and a prolonged time between early infection and the development of genital neoplasia. Abundant data suggest that the clinical expression of genital HPV, including genital neoplasia, occurs more rapidly in the immunocompromised host, and this group of patients may be the ideal population in which to study the natural history of HPV infections. Further, the solid organ transplant population may be the best population to study because of the abrupt and predictable nature of their immunosuppression. Accordingly, this project will establish 3 cohorts of HPV-infected women including renal transplant recipients, women with end-stage renal disease, and HIV- infected women who will be followed prospectively at 4 month intervals with routine gynecologic evaluation and colposcopy, cervicovaginal lavage for HPV-PCR, cultures for genital copathogens, and cervical biopsies as indicated. About 240 women will be evaluated annually, and HPV-positive women will be followed prospectively. The primary focus of this project is to determine the natural course of HPV gene expression, DNA replication, virion production, and viral integration using innovative molecular techniques such as RT-PCR and in situ hybridization, and to correlate these data with clinical, and histopathologic findings in the 3 cohorts. Changes in viral expression will be evaluated according to underlying disease, degree of immunosuppression, and HPV type. We hypothesize that HPV early gene expression will be up-regulated in the immunocompromised cohorts and that these molecular events will correlate with clinical and / or pathologic disease progression. This project represents a multidisciplinary effort including clinical infectious diseases, gynecology / oncology, epidemiology, and molecular virology that is essential to accomplish these goals. The information gained from a detailed analysis of these data could provide important new insights into the early markers of disease progression, and could apply not only to a large immunocompromised population, but to immunocompetent patients as well.