Project 1-Preventing cervical cancer in HIV-infected women

项目1-艾滋病毒感染妇女预防宫颈癌

基本信息

批准号：
10256042
负责人：
DARRON R BROWN
金额：
$ 12.96万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
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/10256042
关键词：
AIDS related cancer AIDS/HIV problem Acetic Acids Aflatoxins Africa Africa South of the Sahara Biopsy CD4 Lymphocyte Count Caring Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cervical dysplasia Clinical Cost Effectiveness Analysis Country DNA Data Databases Detection Exposure to HIV HPV-High Risk Human Papillomavirus Human papilloma virus infection Immune system Immunosuppression Immunosuppressive Agents Impairment Incidence Infrastructure Kenya Literature Malignant Neoplasms Malignant neoplasm of cervix uteri Medical Methods Mycotoxins Natural History Oncogenic Outcome Plasma Policies Prevalence Research Risk Risk Factors Screening procedure Swab Testing Training Uganda Vagina Viral load measurement Virus Visual Woman antiretroviral therapy carcinogenicity cofactor cost design experience high risk improved insight prevent programs reconstitution screening

项目摘要

Abstract In contrast to other HIV-associated cancers, the incidence of cervical cancer has not declined in the era of antiretroviral therapy (ART), and is the most common cancer among Kenyan and Ugandan women. These countries each have high HIV prevalence, which greatly accelerates the progression of cervical cancer, even in women receiving ART and achieving “reconstituted” immune systems. Better methods of screening are needed, and we need to understand cofactors related to HPV infection, the virus that causes cervical cancer. The long-term objective of our project is to help eradicate cervical cancer in HIV-infected Kenyan and Ugandan women. We will test our approach in a study of HIV-infected women. First, we will evaluate HR-HPV DNA testing of self-collected vaginal swabs combined with VIA in detecting biopsy-proven cervical intraepithelial neoplasia grades 2, 3, or worse (CIN 2/3+) in HIV-infected women living in Kenya or Uganda. We hypothesized that detection of biopsy-proven CIN 2/3+ is higher among HIV-infected women with both HR- HPV DNA positivity and VIA abnormality compared to those with only one or neither of these tests positive. Second, we will determine if aflatoxin, a carcinogenic and immunosuppressive compound found in contaminated corn, is a risk factor for oncogenic HPV detection and cervical cancer among HIV-infected Kenyan and Ugandan women. We hypothesize that regardless of HIV-status, aflatoxin is a risk factor for HR- HPV detection, HR-HPV persistence, and biopsy-proven CIN 2/3+, that the impact of aflatoxin on HR-HPV detection, HR-HPV persistence, and biopsy-proven CIN 2/3+ will be significantly greater in HIV-infected women than in HIV-uninfected women, and that the immunosuppressive effects of aflatoxin impair the host’s ability to control HIV in spite of ART use. Accomplishment of our aims will help improve care for all women in Kenya and Uganda, and help in the battle against cervical cancer in HIV-infected women.

抽象的与其他与其他艾滋病毒相关的癌症相反，宫颈癌的事件在这个时代没有下降抗逆转录病毒疗法（ART），是肯尼亚和乌干达妇女中最常见的癌症。这些各个国家的艾滋病毒患病率很高，即使在接受艺术并实现“重构”免疫系统的妇女。更好的筛选方法是需要，我们需要了解与HPV感染有关的辅助因子，这是导致宫颈癌的病毒。我们项目的长期目的是帮助肯尼亚和乌干达的HIV感染的宫颈癌女性。我们将在对感染HIV的妇女的研究中测试我们的方法。首先，我们将评估HR-HPV DNA 测试自我收集的阴道拭子与VIA结合检测活检证明颈内上皮居住在肯尼亚或乌干达的艾滋病毒感染的妇女中，肿瘤2、3或更糟（CIN 2/3+）。我们假设在HR-的HIV感染妇女中，检测活检证实的CIN 2/3+较高与仅一项或两项测试呈阳性的HPV DNA积极性和通过异常相比。其次，我们将确定黄曲霉毒素是在受污染的玉米是HIV感染的致癌HPV检测和宫颈癌的危险因素肯尼亚和乌干达妇女。我们假设，无论艾滋病毒状态如何，黄曲霉毒素都是HR-的危险因素 HPV检测，HR-HPV持久性和活检证实CIN 2/3+，黄曲霉毒素对HR-HPV的影响 HIV感染的检测，HR-HPV持久性和活检证明CIN 2/3+将明显更大女性比在艾滋病毒未感染的妇女中，而黄曲霉毒素的免疫抑制作用损害了宿主的尽管使用艺术，能够控制艾滋病毒。实现我们的目标将有助于改善对所有女性的护理肯尼亚和乌干达，并在艾滋病毒感染的妇女中为与宫颈癌作斗争。