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

• 批准号: 10477367
• 负责人: DARRON R BROWN
• 金额: $ 13万
• 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/10477367
• 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

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 与其他与艾滋病毒相关的癌症相比，宫颈癌的发病率在新时代并没有下降。 抗逆转录病毒疗法（ART）是肯尼亚和乌干达女性中最常见的癌症。这些 每个国家的艾滋病毒感染率都很高，这大大加速了宫颈癌的进展，即使在 接受抗逆转录病毒治疗并实现“重建”免疫系统的女性。更好的筛选方法是 我们需要了解与 HPV 感染（导致宫颈癌的病毒）相关的辅助因子。 我们项目的长期目标是帮助根除感染艾滋病毒的肯尼亚和乌干达的宫颈癌 女性。我们将在一项针对艾滋病毒感染女性的研究中测试我们的方法。首先，我们将评估 HR-HPV DNA 自采集阴道拭子联合VIA检测活检证实的宫颈上皮内瘤变 生活在肯尼亚或乌干达的 HIV 感染女性中的 2 级、3 级或更严重的肿瘤（CIN 2/3+）。我们 假设在患有 HR- 的 HIV 感染女性中，经活检证实的 CIN 2/3+ 检出率更高 HPV DNA 阳性和 VIA 异常与只有一项或两项检测均未呈阳性的患者进行比较。 其次，我们将确定黄曲霉毒素（一种致癌和免疫抑制化合物）是否存在于 受污染的玉米是 HIV 感染者中致癌 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 HIV 状况如何，黄曲霉毒素都是 HR- HPV检测、HR-HPV持续性和活检证实的CIN 2/3+，表明黄曲霉毒素对HR-HPV的影响 HIV 感染者中的检测、HR-HPV 持续性和活检证明的 CIN 2/3+ 将显着增加 女性的感染率高于未感染艾滋病毒的女性，黄曲霉毒素的免疫抑制作用会损害宿主的免疫系统 尽管使用抗逆转录病毒治疗，仍能够控制艾滋病毒。实现我们的目标将有助于改善对所有妇女的护理 肯尼亚和乌干达，帮助感染艾滋病毒的妇女对抗宫颈癌。