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/艾滋病确诊病例占世界的70%，乌干达和肯尼亚的艾滋病毒/艾滋病确诊病例占世界的70%。 其震中（分别为12%和7%的患病率）。在东非，宫颈癌仍然是最常见的癌症之一。 女性常见的恶性肿瘤HIV是宫颈癌发生的一个促成因素， 妇女具有更高的人乳头瘤病毒（HPV）感染的发病率和持续性，宫颈癌， 和宫颈癌前病变。与其他艾滋病毒相关癌症相比，宫颈癌的发病率 在抗逆转录病毒治疗的时代并没有减少。 本申请的核心目的是更好地阐明HPV感染和宫颈癌的自然史 在感染艾滋病毒的妇女中，包括参与致癌作用的辅助因子， 宫颈上皮内瘤变（CIN）LEEP后，并确定新的病毒和细胞生物标志物，将有助于 筛选、分类和治疗。 我们的中心假设是，高危型HPV的发病率、持续性和感染谱在很大程度上取决于 在感染艾滋病毒的东非妇女中，宫颈癌的发病率更高，这解释了宫颈癌发生率更高的原因。 我们进一步假设，这些和其他可改变的因素，如黄曲霉毒素摄入， 并对局部治疗的结果产生不利影响，例如环形电外科切除术（LEEP） 感染艾滋病毒的妇女。 东非HPV和宫颈癌联盟（EACHC）的具体目标是： 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，以建立国际伙伴关系， 对感染艾滋病毒/艾滋病妇女的HPV和宫颈癌进行有影响力的研究 具体目标2。设计和执行三个综合项目，以促进对 导致东非宫颈癌的环境和生物因素： 项目1-预防感染艾滋病毒的妇女患宫颈癌 项目2-了解LEEP术后感染艾滋病毒的妇女的CIN 2+：流行病学和 免疫组化研究 项目3-确定与宫颈发育不良临床进展相关的生物学和病毒因素 感染艾滋病毒的妇女 具体目标3。通过指导和培训计划，提高东非的研究人员能力 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