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

项目摘要 撒哈拉以南非洲的艾滋病毒负担不成比例，占全球感染人数的69%， 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，三分之一的癌症在亚 撒哈拉非洲是由病毒引起的。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， 指出，随着艾滋病毒/艾滋病感染者接受抗逆转录病毒联合疗法治疗的比例增加， 艾滋病毒（PLWH），艾滋病毒相关恶性肿瘤的发生率（即，卡波西肉瘤，非霍奇金 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的发病率没有下降，可能有所上升。 HPV相关恶性肿瘤的研究在很大程度上依赖于实验室检测和组织病理学， 其可以在资源有限的设置中实现。卢旺达/刚果民主共和国/爱因斯坦艾滋病毒相关的HPV- 本申请中提出的肿瘤研究中心（HAMRC）将扩大地理和 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 在刚果民主共和国（DRC）建立伙伴关系，包括非常需要的研究能力，以评估 PLWH中的HPV相关癌症。 该中心建议通过两个项目进行HPV相关恶性肿瘤的主要研究：1）评估 在感染艾滋病毒的年轻女性中进行HPV预防性疫苗接种;以及2）评估HPV感染和疾病 在刚果（金）和卢旺达与艾滋病毒感染者和非艾滋病毒感染者发生性关系的男子中。在两项研究中 我们将研究HPV感染和疾病与当地微生物植物群的相互作用。共享 核心资源通过培养卢旺达的可持续研究能力来实现HAMRC的目标， DRC支持病毒相关癌症的研究。因此，共享的具体目标 资源核心是提供严格的分子诊断分析，以支持对两者影响的研究。 在艾滋病毒感染者中开展与HPV相关的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Au刚果新教大学病理学实验室（实时PCR平台）中重复 对于先前在卢旺达军事医院（RMH）建立的hrHPV分型，在爱因斯坦/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，下一代测序。 3.支持在卢旺达爱因斯坦/RMH研究实验室进一步开发ELISA检测， 使用测定来测量抗HPV 16和HPV 18 IgG抗体滴度， 由弗雷德里克国家癌症研究实验室HPV血清学实验室建立。 拟议的能力建设将包括研究人员和调查人员的人员发展， 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 领导人提出的。

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.