Pediatric HIV and Cancer Epidemiology

儿童艾滋病毒和癌症流行病学

• 批准号: 10657491
• 负责人: Michael E Scheurer
• 金额: $ 17.36万
• 依托单位: BAYLOR 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: 2020-07-25 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657491
• 关键词: 14 year old; AIDS related cancer; Acquired Immunodeficiency Syndrome; Acute; Address; Adult; Africa; Africa South of the Sahara; Biological Markers; Blood; Cancer Burden; Caring; Cells; Child; Childhood; Clinic; Clinical; Clinical Data; Collection; Data; Diagnosis; Disease; Environment; Epidemiology; Future; Goals; HIV; HIV Infections; HIV/AIDS; Herpesviridae; Human Herpesvirus 4; Human Herpesvirus 8; Immune; Immune system; Incidence; Infection; International; Invaded; Kaposi Sarcoma; Laboratories; Life; Literature; Lymphoma; Malignant Childhood Neoplasm; Malignant Neoplasms; Malnutrition; Medicine; Pediatric Hospitals; Pediatric epidemiology; Plasma; Population; Prevalence; Protocols documentation; Recording of previous events; Research; Resources; Risk; Risk Factors; Screening for cancer; Severities; Site; Texas; Time; Update; Viral Load result; Viral Markers; Virus; antiretroviral therapy; biomarker identification; cancer diagnosis; cancer epidemiology; cancer risk; chemokine; clinical risk; cohort; college; comorbidity; cytokine; electronic medical record system; epidemiology study; experience; high risk; high risk population; infection related cancer; novel; pediatric human immunodeficiency virus; risk prediction

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.

项目 1：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 撒哈拉以南非洲地区 (SSA) 承担着儿童艾滋病毒/艾滋病的负担，大约有 170 万儿童艾滋病毒病例中的 90%。尽管近年来已经取得了实质性进展 尽管限制了儿童中艾滋病毒新发病例的数量，但估计仍有 160 万儿童感染艾滋病毒 SSA 中的艾滋病毒。这些感染艾滋病毒的儿童因患病而患癌症的风险更高。 成人中与艾滋病毒相关的恶性肿瘤的流行病学已得到相当广泛的研究；然而，很少有 已经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患恶性肿瘤的风险最高。为了解决这些差距 在 SSA 儿童 HIV 相关恶性肿瘤的流行病学研究中，我们提出以下目标： 1. 通过扩展和更新计算 HIV+ 儿童中癌症的患病率和发病率 一群在 BIPAI 卓越中心接受治疗和随访的 HIV 阳性儿童。 我们将利用 BIPAI CoE 及其附属诊所的高质量电子病历系统 网络以及自 2004 年以来在 CoE 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情况。假设： 1）某些疾病的发生率 14 岁或以下的 HIV 感染儿童中，与感染相关的癌症发病率更高，并且 2) 在该队列的时间范围内，与 HIV 相关的癌症（例如 KS）的发病率低于 历史数据显示，而其他非艾滋病定义的癌症的发病率会更高。 2. 确定临床危险因素对 SSA 儿童 HIV 相关恶性肿瘤风险的影响。 我们将评估风险因素的影响，例如抗逆转录病毒治疗的时机、癌症的艾滋病毒分期 诊断、癌症诊断时的严重急性营养不良以及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。我们还将评估是否有患艾滋病毒相关的风险 恶性肿瘤受感染史和其他合并症的影响。假设：与a相关的因素 儿童艾滋病毒感染的严重程度和早期生活环境是罹患儿科艾滋病毒相关疾病的风险的基础 SSA 的恶性肿瘤。 3. 确定被诊断患有癌症的 HIV+ 儿童中更丰富的血浆生物标志物。 根据文献证据和我们自己的初步数据，我们将比较一组标准 4 组儿童的细胞因子/趋化因子和病毒负荷标记：1) HIV+/癌症+，2) HIV+/癌症-， 3) HIV-/癌症+，以及 4) HIV-/癌症-。目标是确定 HIV+ 儿童癌症风险的生物标志物， 可以与目标 2 中确定的临床因素结合使用，开发一种新的癌症筛查范例 这个高危人群。假设：可检测到特定的癌症和艾滋病毒相关差异 与未患有艾滋病毒相关恶性肿瘤的儿童相比，他们的血浆中存在这种情况。