Partnership to Assess Viral and Immune Landscape Intersections with ONcology for People Living with HIV (PAVILION)

项目总结--总体 合作中心，题为评估病毒和免疫景观与肿瘤学的交叉 (展馆)艾滋病毒携带者计划将汇集经验丰富的研究地点和世界各地- 著名的艾滋病毒、人乳头瘤病毒(HPV)、爱泼斯坦-巴尔病毒(EBV)和癌症研究人员提供一种新颖的 对艾滋病毒相关恶性肿瘤研究中心网络的贡献。展馆的主题是研究 对艾滋病毒携带者男性和女性影响不成比例的未被研究的病毒相关肿瘤 在撒哈拉以南非洲(SSA)。SSA仍然是三分之二艾滋病毒携带者(PLWH)的家园。与HIV相关的 免疫抑制会导致无法控制病毒，从而增加与病毒相关的风险 癌症，甚至在PLWH中使用有效的抗逆转录病毒治疗。长寿老人的预期寿命不断增加 癌症使这种癌症风险复杂化，因为癌症现在是导致PLWH高、低水平死亡的主要原因 资源国。此外，PLWH的癌症治疗结果较差。尽管如此，很少有研究 对LMICs中PLWH的癌症病因和癌症结局进行了研究，但很少关注HPV。 宫颈外解剖部位的癌症，以及极少关于结膜肿瘤疑似病毒病因学的研究。 因此，展馆将重点关注由HPV(肛门、宫颈、口咽、阴茎、 和外阴癌)以及EBV在结膜鳞状细胞癌中的潜在作用 非均衡性在PLWH中更高，并导致相当大的发病率和死亡率。 Pavilion的总体目标是提供必要的数据，为预防和治疗策略提供信息 降低SSA地区PLWH人群的癌症负担。展馆包括南非和南非的合作伙伴 津巴布韦、美国的多家机构，以及德国的DKFZ。值得注意的是，津巴布韦和南非 是非洲艾滋病毒流行率最高的国家之一，而且癌症负担迅速增加，主要是 由感染相关的癌症组成。作为合作伙伴，我们有着长期的合作，出色的 研究领导，癌症研究的相互优先顺序，以及机构和联盟的经验 这将促进科学发现的翻译，以实现我们的目标。支持这一目标的具体目标是： 目标1：与研究基础设施建立多国伙伴关系(行政和协调， 中心实验室、数据管理和统计核心)，以进行协作、创新和 在SSA的PLWH中推进感染相关癌症防治的有影响力的研究 目标2：了解可归因于特定致癌病毒(即HPV、EBV)的肿瘤比例， 表征肿瘤的免疫微环境是HIV背景下独有的，并且更完整 对SSA中PLWH和癌症的临床结果的理解(项目1和2) 目标3：通过积极的指导和培训方案建设能力(行政和协调以及 合作机构的早期和初级教师的发展核心)

PROJECT SUMMARY – OVERALL The partnership center, entitled Partnership to Assess Viral and Immune Landscape Intersections with Oncology (PAVILION) for People Living with HIV Program will bring together experienced research sites and world- renowned HIV, human papillomavirus (HPV), Epstein Barr Virus (EBV), and cancer researchers to offer a novel contribution to the HIV-Associated Malignancies Research Center network. The PAVILION theme is research of understudied, virus-associated tumors that disproportionately impact men and women living with HIV in sub-Saharan Africa (SSA). SSA remains home to two thirds of people living with HIV (PLWH). HIV-related immunosuppression results in an inability to control viruses and therefore a higher risk of virus-associated cancer, even among PLWH on effective antiretroviral therapy. The increasing life-expectancy of PLWH compounds this cancer risk as cancer is now a leading cause of mortality among PLWH in both high and low resource countries. Furthermore, PLWH experience poorer cancer treatment outcomes. Despite this, few studies of cancer etiology and cancer outcomes among PLWH in LMICs have been conducted, with little focus on HPV cancers at extra-cervical anatomic sites and very few studies of a suspected viral etiology for conjunctival tumors. PAVILION will therefore focus on the full range of cancers caused by HPV (anal, cervical, oropharyngeal, penile, and vulvar cancers) and the potential role of EBV in conjunctival squamous cell carcinoma - cancers that are disproportionality higher among PLWH, and which result in substantial morbidity and mortality. The overall goal of PAVILION is to provide the data necessary to inform prevention and therapeutic strategies to reduce the burden of cancers among PLWH in SSA. PAVILION includes partners in South Africa and Zimbabwe, multiple institutions in the US, and the DKFZ in Germany. Notably, Zimbabwe and South Africa have among the highest prevalence of HIV in Africa and have a rapidly increasing cancer burden that is largely comprised of infection-associated cancers. As a partnership, we have long standing collaborations, outstanding research leadership, mutual prioritization of the cancers to study, and institutional and consortium experience that will facilitate translation of scientific findings to achieve our goal. Specific Aims supporting this goal are: Aim 1: Establish a multi-national partnership with research infrastructure (Administrative & Coordinating, Central Laboratory, and Data Management & Statistics Cores) to conduct collaborative, innovative, and impactful research that advances prevention and treatment of infection-related cancers among PLWH in SSA Aim 2: Understand the fraction of tumors attributable to specific oncogenic viruses (i.e., HPV, EBV), the characterization of the immune microenvironment of tumors unique to the setting of HIV, and a more complete understanding of clinical outcomes for PLWH and cancer in SSA (Projects 1 and 2) Aim 3: Build capacity through active mentorship and training programs (Administrative & Coordinating and Developmental Cores) for early stage and junior faculty at partnership institutions