Improving the Accuracy of Diagnosis of Cancer in Children with HIV Infection

项目2：提高艾滋病毒感染儿童癌症诊断的准确性 项目2的目标是评估和实施可复制和可持续的新战略 在撒哈拉以南非洲（SSA）的治疗地点，以改善艾滋病毒相关儿科疾病的实时诊断。 因为这是循证治疗和临床/转化研究的先决条件。 在撒南非洲，儿童癌症的诊断是一项重大挑战，因为当地熟练人员稀缺， 用于获得组织活组织检查的设施和用于病理学分析的实验室平台。结果是，对于 许多怀疑患有癌症的儿童仅根据临床特征作出诊断。如果活检是 在获得的样品中，使用苏木精和伊红（H&E）染色的形态学检查通常是唯一进行的测试。 我们在乌干达、马拉维、坦桑尼亚的BIPAI中心对324名艾滋病毒感染者和诊断为KS的患者进行了研究， 2008 - 2014年，在博茨瓦纳，141名（43%）儿童是根据临床病史诊断的， 只是考试。该项目的总体目标是实施和评价统一的诊断方法， PARCA网站的战略。 目的1：评价目前乌干达全球希望组织活检的充分性和诊断准确性 儿科癌症肿瘤的诊断策略。我们将回顾评估充足的比例 在400名患有HIV相关癌症的儿童中进行活检，并重复或升级为开放手术活检。 为了确定当前诊断策略的准确性，我们将进行金标准诊断测定 根据美国标准，对这400例病例的存档FFPE组织进行检测。 目标2：确定跨多个站点标准化诊断算法的可行性， 在马拉维实施类似的算法。我们将在马拉维实施类似的诊断方法， 培训医务人员使用类似的活检策略并扩展流式细胞术和免疫组化抗体 模拟在乌干达进行的实验。确保各研究中心准备工作的准确性和一致性 为了在整个SSA站点实施标准化的癌症治疗和研究方案，我们将 实施虚拟病理学平台以实现图像共享和集中审查。虚拟病理学 该网络还将作为儿科病理学家和技术人员持续培训的平台。 目标3：通过设计、测试和实施，提高SSA站点癌症诊断的准确性 新的诊断方法。我们将测试和验证新的分子检测方法， 生物标志物，以提高诊断的及时性和特异性，使用平台和程序， 可持续发展的战略。将考虑成本、复杂性和周转时间。

Project 2: Improving the Accuracy of Diagnosis of Cancer in Children with HIV Infection The goal of Project 2 is to evaluate and implement novel strategies that are reproducible and sustainable across treatment sites in sub-Saharan Africa (SSA) to improve real-time diagnosis of HIV-associated pediatric cancers, because this is a prerequisite for evidence-based treatment and clinical/translational research. Diagnosis of cancer in children in SSA is a major challenge because of scarcity of local skilled personnel, facilities for obtaining tissue biopsies, and laboratory platforms for pathology analysis. The result is that for many children with suspected cancer a diagnosis is made based on clinical features only. If a biopsy is obtained, morphological examination using Hematoxylin & Eosin (H&E) stain is often the only test performed. In our study of 324 with HIV infection and diagnosed with KS at BIPAI centers in Uganda, Malawi, Tanzania and Botswana from 2008 – 2014, 141 (43%) of the children were diagnosed based on clinical history and examination only. The overarching aim of this project is to implement and evaluate harmonized diagnostic strategies in PARCA sites. Aim 1: Evaluate the adequacy of biopsies and diagnostic accuracy of the current Global HOPE Uganda diagnostic strategy for pediatric cancer tumors. We will retrospectively assess the proportion of adequate biopsies, and repeat or escalation to open surgical biopsy among 400 children with HIV-associated cancers. To determine the accuracy of the current diagnostic strategy, we will perform gold-standard diagnostic assays by United States standards on archived FFPE tissues from these 400 cases. Aim 2: Determine the feasibility of standardizing the diagnostic algorithm across multiple sites by implementing a similar algorithm in Malawi. We will implement a similar diagnostic approach in Malawi by training medical personnel to use a similar biopsy strategy and expanding the flow cytometry and IHC antibody panels to mimic those performed in Uganda. To ensure accuracy and consistency across sites in preparation for implementation of standardized cancer treatment and research protocols across SSA sites, we will implement a virtual pathology platform to enable sharing and central review of images. The virtual pathology network will also serve as a platform for ongoing training of pediatric pathologists and technicians. Aim 3: Improve accuracy of cancer diagnosis at SSA sites by designing, testing, and implementing novel diagnostic methods. We will test and validate novel molecular assays of established diagnostic biomarkers to improve timeliness and specificity of the diagnosis using platforms and procedures that are sustainable in the SSA setting. Consideration will be given to cost, complexity, and turnaround time.