Pediatric HIV and Cancer Epidemiology

项目1：#年艾滋病毒/艾滋病背景下儿童癌症的流行病学和风险预测 非洲 撒哈拉以南非洲(SSA)不成比例地承担着儿童艾滋病毒/艾滋病的负担，大约有 在170万儿童艾滋病毒感染病例中，有90%。虽然近年来在以下方面取得了实质性进展 限制儿童中艾滋病毒新病例的数量，估计仍有160万儿童患有艾滋病毒 SSA中的HIV病毒。这些感染艾滋病毒的儿童因其疾病而患癌症的风险更高。 成人中艾滋病毒相关恶性肿瘤的流行病学已经得到了相当广泛的研究；然而，很少有 对感染艾滋病毒的儿童中的癌症进行了流行病学研究。我们的长期目标是 确定哪些感染艾滋病毒的儿童罹患恶性肿瘤的风险最高。要填补这些差距， 在SSA儿童艾滋病毒相关恶性肿瘤的流行病学研究中，我们提出了以下目标： 1.通过扩展和更新计算HIV+儿童的癌症患病率和发病率 在BIPAI卓越中心接受治疗和跟踪的一群HIV+儿童。 我们将利用北派中心和附属诊所的高质量电子病历系统 网络和自2004年以来在COES接受治疗的大量艾滋病毒感染儿童 了解癌症在这一高危人群中的分布。假设：1)某些疾病的发病率 感染相关癌症在14岁或以下感染艾滋病毒的儿童中将更高，2) 在这个队列的时间范围内，艾滋病毒相关癌症(如KS)的发病率比 历史数据，而其他非艾滋病定义的癌症的发病率将更高。 2.确定临床危险因素对儿童SSA中HIV相关恶性肿瘤风险的影响。 我们将评估风险因素的影响，如抗逆转录病毒治疗的时机、艾滋病毒在癌症中的阶段 诊断、癌症诊断时的严重急性营养不良以及与艾滋病毒相关的地理气候差异 居住在SSA的儿童的恶性肿瘤风险。我们还将评估感染艾滋病毒的风险是否与 恶性肿瘤受感染史和其他合并症的影响。假设：与 儿童HIV感染严重程度和早期生活环境是发展为儿童HIV相关疾病的危险因素 SSA中的恶性肿瘤。 3.在被诊断为癌症的HIV+儿童中，确定更丰富的血浆生物标志物。 基于文献中的证据和我们自己的初步数据，我们将比较一组标准的 在4组儿童中，细胞因子/趋化因子和病毒负荷的标志物：1)HIV+/癌症+，2)HIV+/癌症-， 3)HIV-/癌症+，和4)HIV-/癌症-。目标是确定HIV+儿童中癌症风险的生物标记物 可以利用目标2中确定的临床因素来开发一种新的癌症筛查范例 这些高危人群。假设：可以检测到与癌症和艾滋病毒相关的特定差异 患上艾滋病毒相关恶性肿瘤的儿童与未患此病的儿童相比，其血浆中的蛋白质含量更高。

Project 1: Epidemiology of and Risk Prediction for Childhood Cancers in the Context of HIV/AIDS in Africa Sub-Saharan Africa (SSA) disproportionately bears the burden of pediatric HIV/AIDS, having approximately 90% of the 1.7 million pediatric cases of HIV. While substantial progress has been made in recent years to limit the number of new cases of HIV among children, there are still an estimated 1.6 million children living with HIV in SSA. These HIV-infected children are at a higher risk for developing cancer as a result of their disease. The epidemiology of HIV-related malignancies among adults has been fairly extensively studied; however, few epidemiologic studies on cancer among children with HIV have been conducted. Our long-term goal is to determine which HIV-infected children are at highest risk of developing a malignancy. To address these gaps in the epidemiology of pediatric HIV-related malignancies in SSA, we propose the following aims: 1. Calculate the prevalence and incidence of cancers among HIV+ children by expanding and updating a cohort of HIV+ children who are treated and followed at the BIPAI Centers of Excellence. We will leverage both the high-quality electronic medical record system in the BIPAI CoE and affiliated clinic network and the large population of HIV-infected children who have been treated at the CoEs since 2004 to understand the distribution of cancers in this high-risk population. Hypotheses: 1) The incidence of certain infection-related cancers will be higher among HIV-infected children age 14 years or younger, and 2) there will be a lower incidence of HIV-associated cancers (e.g., KS) over the timeframe of this cohort compared to historical data, while the incidence of other non-AIDS defining cancers will be higher. 2. Determine the impact of clinical risk factors on pediatric HIV-related malignancy risk in SSA. We will assess the impact of risk factors such as timing of anti-retroviral treatment, HIV stage at cancer diagnosis, severe acute malnutrition at cancer diagnosis, and geoclimatic differences on HIV-related malignancy risk of children living in SSA. We will also assess whether risk of developing HIV-related malignancies is influenced by history of infections and other co-morbidities. Hypothesis: Factors related to a child's HIV infection severity and early life environment underlie risk of developing pediatric HIV-related malignancies in SSA. 3. Identify plasma biomarkers that are more abundant among HIV+ children diagnosed with cancer. Based on evidence from the literature and our own preliminary data, we will compare a standard set of cytokines/chemokines, and markers of virus burden, in 4 groups of children: 1) HIV+/Cancer+, 2) HIV+/Cancer-, 3) HIV-/Cancer+, and 4) HIV-/Cancer-. The goal is to identify biomarkers of cancer risk in HIV+ children that could be utilized with the clinical factors identified in Aim 2 to develop a novel paradigm for cancer screening in this high-risk population. Hypothesis: There are both specific cancer- and HIV-related differences detectable in the plasma of children who develop HIV-related malignancies compared to those who do not.