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

东非艾滋病毒/艾滋病女性 HPV 和宫颈癌联盟

• 批准号: 10084048
• 负责人: DARRON R BROWN
• 金额: $ 99.53万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-07 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10084048
• 关键词: AIDS related cancer; AIDS/HIV problem; Acetic Acids; Aflatoxins; Africa; Africa South of the Sahara; African; Biological; Biological Factors; Biological Markers; Biometry; Cervical; Cervical Cancer Screening; Cervical Intraepithelial Neoplasia; Cervical dysplasia; Cervix Neoplasms; Clinical; Communicable Diseases; Data; Development; Diagnosis; Environmental Risk Factor; Epidemiology; Goals; HIV; HPV-High Risk; Human Papillomavirus; Human papilloma virus infection; Incidence; Ingestion; Institutes; Kenya; Knowledge; Lesion; Local Therapy; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Mentors; Natural History; Nurses; Outcome; Physicians; Pilot Projects; Prevalence; Research; Research Infrastructure; Research Personnel; Resource Sharing; Scientist; Testing; Training; Training Programs; Translational Research; Triage; Uganda; Viral; Visual; Woman; antiretroviral therapy; carcinogenesis; career; cervical carcinogenesis; cofactor; data management; design; international partnership; loop electrosurgical excision procedure; low and middle-income countries; premalignant; prevent; programs; screening; viral DNA

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

总体摘要 撒哈拉以南非洲地区占世界艾滋病毒/艾滋病确诊病例的 70%，其中乌干达和肯尼亚均处于这一水平。 其震中（患病率分别为 12% 和 7%）。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HIV感染者宫颈癌发生的一个促成因素 女性人乳头状瘤病毒（HPV）感染、宫颈癌、 和宫颈癌前病变。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时代并未衰落。 该应用的核心目标是更好地阐明HPV感染和宫颈癌的自然史 在感染艾滋病毒的女性中，包括参与致癌作用的辅助因子、癌症的持续存在和进展 LEEP 后的宫颈上皮内瘤变 (CIN)，并确定新的病毒和细胞生物标志物，以帮助 在筛查、分诊和治疗方面。 我们的中心假设是，高危 (HR) HPV 的发病率、持续性和谱系与 感染艾滋病毒的东非妇女的比例更高，这解释了宫颈肿瘤发病率较高的原因。 我们进一步假设这些和其他可改变的因素，例如黄曲霉毒素的摄入，不成比例地 并对局部治疗的结果产生不利影响，例如环形电外科切除手术（LEEP） 感染艾滋病毒的女性。 东非女性 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. 建立可持续的研究基础设施，以便国际伙伴关系开展 对感染艾滋病毒/艾滋病的女性中的 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，以提高人们的知识 导致东非宫颈癌的环境和生物因素： 项目1-预防艾滋病毒感染妇女的宫颈癌 项目 2 - 了解 LEEP 后 HIV 感染女性中的 CIN2+：流行病学和 免疫组织化学研究 项目 3 - 确定与宫颈发育不良临床进展相关的生物和病毒因素 感染艾滋病毒的女性 具体目标 3. 通过指导、培训计划提高东非研究人员的能力 和有针对性的试点项目