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: 10084053
• 负责人: DARRON R BROWN
• 金额: $ 13.09万
• 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/10084053
• 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.

摘要 与其他艾滋病毒相关的癌症相比，宫颈癌的发病率在2005年没有下降。 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 每个国家都有很高的艾滋病毒感染率，这大大加速了宫颈癌的进展，即使在 接受抗逆转录病毒疗法和实现"重建"免疫系统的妇女。更好的筛选方法是 我们需要了解与HPV感染相关的辅助因子，HPV感染是导致宫颈癌的病毒。 我们项目的长期目标是帮助肯尼亚和乌干达艾滋病毒感染者根除宫颈癌。 妇女我们将在一项对艾滋病毒感染妇女的研究中测试我们的方法。首先，我们将评估HR-HPV DNA 阴道拭子联合宫颈癌细胞学检查诊断宫颈上皮内瘤样病变 在肯尼亚或乌干达的HIV感染妇女中，肿瘤等级为2、3或更差（CIN 2/3+）。我们 假设活检证实的CIN 2/3+的检出率在HR- HPV DNA阳性和VIA异常相比，只有一个或没有这些测试阳性。 其次，我们将确定是否黄曲霉毒素，一种致癌和免疫抑制化合物发现， 受污染的玉米，是艾滋病毒感染者中致癌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，无论艾滋病毒感染状况如何，黄曲霉毒素都是HR的危险因素， HPV检测、HR-HPV持续存在和活检证实的CIN 2/3+，即黄曲霉毒素对HR-HPV的影响 检测，HR-HPV持续存在，活检证实CIN 2/3+将显着高于HIV感染者 与未感染HIV的女性相比，黄曲霉毒素的免疫抑制作用损害了宿主的免疫功能。 尽管使用了抗逆转录病毒疗法，但仍有能力控制艾滋病毒。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，并帮助感染艾滋病毒的妇女防治宫颈癌。