The East Africa Consortium for HPV and Cervical Cancer in Women living with HIV/AIDS

总体摘要 撒哈拉以南非洲地区的艾滋病毒/艾滋病确诊病例占全球的70%，乌干达和肯尼亚的 其震中(患病率分别为12%和7%)。在东非，宫颈癌仍然是发病率最高的疾病之一 女性常见的恶性肿瘤。HIV是HIV感染者宫颈癌发生的一个促成因素 人乳头瘤病毒(HPV)感染、宫颈癌、 和子宫颈癌前病变。与其他与艾滋病毒相关的癌症相比，宫颈癌的发病率 在抗逆转录病毒治疗的时代并没有下降。 这项应用的核心目标是更好地阐明hpv感染和宫颈癌的自然病史。 在感染艾滋病毒的妇女中，包括参与癌症发生、持续和进展的辅助因素 LEEP后宫颈上皮内瘤变(CIN)，并确定新的病毒和细胞生物标记物将有助于 在筛查、分类和治疗方面。 我们的中心假设是，高危(HR)HPV的发病率、持久性和谱系基本上是 在感染艾滋病毒的东非妇女中发病率更高，这就解释了宫颈肿瘤发病率较高的原因。 我们进一步假设，这些因素和其他可改变的因素，如黄曲霉毒素摄入量，不成比例地 并对局部治疗的结果产生不利影响，如电环切除手术(LEEP) 在感染艾滋病毒的妇女身上。 东非妇女HPV和宫颈癌联盟(EACHC)的具体目标 艾滋病毒/艾滋病是： 具体目标1.建立一个可持续的研究基础设施，供国际伙伴关系开展 HIV/AIDS患者HPV与宫颈癌的相关性研究 具体目标2.设计和执行三个综合项目，以增进对 导致东非宫颈癌的环境和生物因素： 项目1--预防感染艾滋病毒妇女的宫颈癌 项目2-了解LEEP术后感染HIV的妇女中的CIN2+：流行病学和 免疫组织化学研究 项目3-确定与宫颈异型增生临床进展相关的生物学和病毒因素 在感染艾滋病毒的妇女中 具体目标3.通过指导、培训方案提高东非研究人员的能力 和有针对性的试点项目

Overall Abstract Sub-Saharan Africa contains 70% of the world’s diagnosed cases of HIV/AIDS, with both Uganda and Kenya at its epicenter (12% and 7% prevalence, respectively). Within East Africa, cervical cancer remains one of the most common malignancies in women. HIV is a contributing factor for cervical carcinogenesis with HIV-infected women having a greater incidence and persistence of human papilloma virus (HPV) infections, cervical cancer, and precancerous cervical lesions. In contrast to other HIV-associated cancers, the incidence of cervical cancer has not declined in the era of antiretroviral therapy. The core objective of this application is to better elucidate the natural history of HPV infection and cervical cancer in HIV-infected women, including the cofactors involved in carcinogenesis, the persistence and progression of cervical intraepithelial neoplasia (CIN) after LEEP, and to identify new viral and cellular biomarkers that will assist in screening, triage and treatment. Our central hypothesis is that the incidence, persistence, and spectrum of high risk (HR) HPV are substantially greater in HIV-infected East African women, and that this explains the higher incidence of cervical neoplasia. We further hypothesize that these and other modifiable factors, such as aflatoxin ingestion, disproportionately and adversely influence outcomes of local therapies such as Loop Electrosurgical Excision Procedure (LEEP) in HIV-infected women. The specific aims for the East Africa Consortium for HPV and Cervical Cancer (EACHC) in Women Living with HIV/AIDS are: Specific Aim 1. To establish a sustainable research infrastructure for an international partnership to conduct impactful research in HPV and cervical cancer in women living with HIV/AIDS Specific Aim 2. To design and execute three integrated projects that advance the knowledge of the environmental and biologic factors leading to cervical cancer in East Africa: Project 1- Preventing cervical cancer in HIV-infected women Project 2- Understanding CIN2+ among HIV infected women after LEEP: An epidemiological and immunohistochemical study Project 3- Determining biological and viral factors associated with clinical progression of cervical dysplasia in HIV-infected women Specific Aim 3. To increase the research workforce capacity in East Africa through mentoring, training programs and targeted pilot projects