Einstein/Rwanda/DRC Consortium for Research in HIV/HPV/ Malignancies

爱因斯坦/卢旺达/刚果民主共和国艾滋病毒/HPV/恶性肿瘤研究联盟

• 批准号: 10267220
• 负责人: Kathryn M. Anastos
• 金额: $ 8.34万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267220
• 关键词: AIDS related cancer; Address; Africa; Africa South of the Sahara; Antibody titer measurement; Bioinformatics; Biological Assay; Cancer Etiology; Collaborations; Congo; Consent; Data; Democratic Republic of the Congo; Development; Disease; Doctor of Philosophy; Enzyme-Linked Immunosorbent Assay; Epidemic; Fostering; Funding; Funding Opportunities; Genotype; Geography; Goals; HIV; HIV Infections; HPV-High Risk; Histopathology; Human Microbiome; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human Resources; Human papilloma virus infection; Human papillomavirus 16; Human papillomavirus 18; Immunoglobulin G; Incidence; Individual; Infection; Investigation; Kaposi Sarcoma; Laboratories; Laboratory Research; Lead; Leadership; Malignant Neoplasms; Malignant neoplasm of anus; Measurement; Measures; Military Hospitals; Molecular Diagnostic Testing; Non-Hodgkin' s Lymphoma; Pathology; Patients; Persons; Preventative vaccination; Protocols documentation; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resource Sharing; Resources; Rwanda; Sampling; Serology; System; Teaching Hospitals; Testing; Time; Translational Research; Universities; University Hospitals; Viral; Viral Load result; Woman; aged; anticancer research; antiretroviral therapy; base; cervical and anal cancer; men who have sex with men; microbiome analysis; microbiome research; microbiota; molecular diagnostics; molecular pathology; next generation sequencing; tool; virus related cancer; young woman

PROJECT SUMMARY Sub-Saharan Africa carries a disproportionate burden of HIV, with 69% of infections globally, as well as a high burden of virally induced malignancies, even before the HIV epidemic. Currently a third of all cancers in Sub- Saharan Africa are virally induced. While data from Africa are scant, evidence from other parts of the world indicates that with increasing rates of treatment with combination antiretroviral therapy for persons living with HIV (PLWH), the incidence of HIV-associated malignancies (i.e., Kaposi’s Sarcoma, non-Hodgkin’s Lymphoma) has declined dramatically. However, cancers caused by human papillomavirus (HPV), specifically invasive cervical cancer and anal cancer, have not declined and may have increased. Investigations of HPV-related malignancies are heavily dependent on laboratory testing and histopathology, which can be implemented in resource limited settings. The Rwanda/DRC/Einstein HIV-Associated HPV- Malignancies Research Center (HAMRC) proposed in this application will extend both the geographic and the scientific scope of our research and capacity-building activities. We will leverage our existing HIV research partnerships in the Democratic Republic of Congo (DRC) to include much desired research capacity to assess HPV-related cancers in PLWH. The Center proposes major studies of HPV-related malignancies through two projects: 1) evaluating the impact of HPV prophylactic vaccination in young women living with HIV; and 2) assessing HPV infection and disease in Congolese (DRC) and Rwandan men who have sex with men with and without HIV infection. In both studies we will investigate the interactions of HPV infection and disease with the local microbial flora. The Shared Resources Core addresses the goal of the HAMRC by fostering sustainable research capacity in Rwanda and the DRC to support investigation of viral-associated cancers. Thus, the specific aims of the Shared Resources Core are to provide rigorous molecular diagnostic analyses to support studies of the impact of both HAMRC projects, and to increase capacity to conduct research in HPV-related malignancies in PLWH in Rwanda and the DRC, and will specifically: 1. Replicate in the Pathology Laboratory at Université Protestante au Congo, the real-time PCR platform for hrHPV typing previously established at Rwanda Military Hospital (RMH), in the Einstein/RMH Research Laboratory. 2. Develop at the Rwanda Military Hospital (RMH), in the Einstein/RMH Research Laboratory, and in collaboration with the University of Rwanda, next generation sequencing. 3. Support further development of ELISA testing in Rwanda, at the Einstein/RMH Research Laboratory, using an assay to measure anti-HPV16 and HPV18 IgG antibody titers implementing a protocol established by the Frederick National Laboratory of Cancer Research HPV Serology Laboratory. The proposed capacity building will include personnel development of both research staff and investigators and will efficiently leverage existing research infrastructure previously developed in large part by the efforts of the proposed HARMC leadership.

项目概要 撒哈拉以南非洲地区的艾滋病毒负担过重，占全球感染率的 69%，而且艾滋病毒感染率也很高 病毒引起的恶性肿瘤的负担，甚至在艾滋病毒流行之前。目前，三分之一的癌症发生在亚 撒哈拉非洲是病毒诱发的。虽然来自非洲的数据很少，但来自世界其他地区的证据 表明，随着患有艾滋病的人接受联合抗逆转录病毒治疗的比例不断增加 HIV (PLWH)，与 HIV 相关的恶性肿瘤（即卡波西肉瘤、非霍奇金氏肉瘤）的发病率 淋巴瘤）急剧下降。然而，由人乳头瘤病毒 (HPV) 引起的癌症，特别是 浸润性宫颈癌和肛门癌并未下降，反而可能有所增加。 HPV 相关恶性肿瘤的调查在很大程度上依赖于实验室检测和组织病理学， 可以在资源有限的环境中实施。卢旺达/刚果民主共和国/爱因斯坦 HIV 相关 HPV- 本申请中提议的恶性肿瘤研究中心 (HAMRC) 将扩展地理和范围 我们的研究和能力建设活动的科学范围。我们将利用现有的艾滋病毒研究 刚果民主共和国 (DRC) 的合作伙伴关系包括许多期望的研究能力，以评估 PLWH 中的 HPV 相关癌症。 该中心提议通过两个项目对 HPV 相关恶性肿瘤进行主要研究：1) 评估影响 对感染艾滋病毒的年轻女性进行 HPV 预防性疫苗接种的情况； 2) 评估 HPV 感染和疾病 与感染或未感染艾滋病毒的男性发生性关系的刚果（金）和卢旺达男性。在这两项研究中 我们将研究 HPV 感染和疾病与当地微生物菌群的相互作用。共享的 资源核心通过培养卢旺达和卢旺达的可持续研究能力来实现 HAMRC 的目标 刚果民主共和国支持病毒相关癌症的调查。因此，共享的具体目标 核心资源将提供严格的分子诊断分析，以支持对两者影响的研究 HAMRC 项目，并提高在 PLWH 中开展 HPV 相关恶性肿瘤研究的能力 卢旺达和刚果民主共和国，并将具体： 1. 在刚果新教大学病理学实验室中进行实时 PCR 平台复制 用于先前在卢旺达军事医院 (RMH) 建立的 hrHPV 分型，位于 Einstein/RMH 研究实验室。 2. 在卢旺达军事医院 (RMH)、爱因斯坦/RMH 研究实验室和 与卢旺达大学合作，进行下一代测序。 3. 支持卢旺达爱因斯坦/RMH 研究实验室进一步开发 ELISA 检测， 使用测定来测量实施方案的抗 HPV16 和 HPV18 IgG 抗体滴度 由弗雷德里克国家癌症研究实验室建立的HPV血清学实验室。 拟议的能力建设将包括研究人员和调查人员的人员发展以及 将有效地利用现有的研究基础设施，这些基础设施以前在很大程度上是由 建议 HARMC 领导。