The role of Epstein Barr Virus and Human Papilloma Virus Co-infection in Conjunctival Squamous Cell Carcinoma.

EB 病毒和人乳头瘤病毒联合感染在结膜鳞状细胞癌中的作用。

• 批准号: 10302985
• 负责人: Tarik Gheit
• 金额: $ 19.86万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302985
• 关键词: Address; Africa; Africa South of the Sahara; African; B-Lymphocytes; Biological Assay; Cells; Conjunctival Squamous Cell Carcinoma; Country; DNA; Data; Detection; Development; Diagnosis; Disease; Epithelial; Epithelial Cells; Epstein-Barr Virus Infections; Etiology; Experimental Models; Eye diseases; Future; Geographic Distribution; Geographic Locations; Geography; HIV; HIV Seronegativity; HIV Seropositivity; Histologic; Histopathology; Hospitals; Human Herpesvirus 4; Human Papillomavirus; Human papilloma virus infection; Immunosuppression; In Situ; In Situ Hybridization; Incidence; Infection; Infectious Agent; International Agency for Research on Cancer; Intervention; Investigation; LMP1; Laboratories; Link; Location; Malignant - descriptor; Malignant Neoplasms; Methods; Non-Malignant; Nucleic Acids; Oncogenic; Oncogenic Viruses; Pathology; Patients; Pilot Projects; Policies; Population; Prevalence; Prevention; Private Hospitals; Privatization; Research; Research Design; Resources; Retrospective Studies; Risk Factors; Role; Sampling; Study models; T-Lymphocyte; Time; Tissue Sample; Tissues; Transcript; Ultraviolet Rays; Viral; Virus; Virus Diseases; Zimbabwe; base; burden of illness; case control; cell type; co-infection; disorder prevention; effective intervention; histological specimens; innovation; insight; novel; ocular surface squamous neoplasia; protein expression; public health research; recruit; screening; sex; synergism; tool; tumor; tumor microenvironment; viral DNA; viral RNA

PROJECT SUMMARY Conjunctival Squamous Cell Carcinoma (SCC) is a malignant disease of the eyes, classified under ocular surface squamous neoplasia (OSSN) (Gichuhi et al. 2015). Incidence of conjunctival SCC has a geographic variability, with high incidence rates occurring in Africa (about 1.3 people per 100,000 population- year), whilst it is relatively rare in other regions of the world (about 0.1 people per 100,000 population-year) (Gichuhi and Sagoo 2016; Gichuhi et al. 2013). We propose to evaluate, for the first time, the role of infectious agents, Human Papilloma Virus (HPV) and Epstein Barr Virus (EBV) in conjunctival SCC in Zimbabwe. This will build upon our recent preliminary data (Galati et al. 2020), where high rates of both Epstein-Barr virus (EBV), 64% and beta human papillomavirus (HPV), 61% in tissue from Ugandan patients with conjunctival SCC, were detected. Three aims will be addressed in the current proposed research. 1. Compare the presence of beta HPV and EBV in tissue samples from histologically confirmed conjunctival SCC patients (cases) versus cancer-free controls with non-malignant pathologies recruited from a tertiary hospital and two private laboratories in Harare, Zimbabwe. 2. Determine the prevalence of viral oncogenic protein expression (e.g., E6 for HPV and LMP1 for EBV) in conjunctival SCC tissues, 3. Explore the location of EBV transcripts across different cell types (B-cells, T-cells and epithelial cells) in conjunctival SCC FFPE tissue samples, stratified by HPV co-infection and HIV status. The study design will be a case-control retrospective study, retrieving an estimated 200 consecutive cancer samples (cases) and 200 cancer free controls. Cases and controls will be matched by sex, age (+/- 10 years) and where possible HIV status with histologically confirmed diagnosis between 1 January 2015 and 31 January 2020 from a central tertiary histopathology laboratory in Harare Zimbabwe, where most provincial and private hospitals refer their samples to. Viral DNA and RNA will be detected in epithelial and/or B and T cells from FFPE samples by PCR-based assays and in situ-hybridization. Our study will build on our strong preliminary data and is anticipated to provide evidence for the involvement of a unique combination of infectious agents (EBV/HPV) in conjunctival SCC. Our findings will offer new opportunities for prevention and screening interventions aimed at populations in Africa in which this malignancy is more common.

项目摘要 结膜鳞状细胞癌（SCC）是一种眼部恶性疾病， 表面鳞状细胞瘤（OSSN）（Gichuhi et al. 2015）。结膜鳞状细胞癌的发病率具有地理分布 变异性，非洲发病率高（每10万人口年约1.3人）， 在世界其他地区相对罕见（每10万人口年约0.1人）（吉丘希和 Sagoo 2016; Gichuhi等人2013）。我们建议首次评估传染源的作用， 津巴布韦结膜鳞状细胞癌中的人乳头状瘤病毒（HPV）和爱泼斯坦巴尔病毒（EBV）。这将构建 根据我们最近的初步数据（加拉蒂等人，2020），其中EB病毒（EBV）的高比率为64%， 和β型人乳头瘤病毒（HPV），61%来自乌干达结膜SCC患者的组织， 检测到 在目前拟议的研究中，将解决三个目标。 1.比较组织学证实的组织样本中β HPV和EBV的存在， 结膜SCC患者（例）与非恶性病理学的无癌对照 从津巴布韦哈拉雷的一家三级医院和两个私人实验室招募。 2.确定病毒致癌蛋白表达的流行率（例如，HPV的E6和EBV的LMP 1） 在结膜SCC组织中， 3.探索EBV转录本在不同细胞类型（B细胞、T细胞和上皮细胞）中的位置 在结膜SCC FFPE组织样品中，通过HPV共感染和HIV状态分层。 研究设计将是一项病例对照回顾性研究，检索估计200例连续癌症 样本（病例）和200例无癌对照。病例和对照将按性别、年龄（+/- 10岁）匹配 2015年1月1日至2016年1月31日期间， 2020年1月，来自津巴布韦哈拉雷的一个中央三级组织病理学实验室， 私家医院会把他们的样本将在上皮细胞和/或B和T细胞中检出病毒DNA和RNA 通过基于PCR的测定和原位杂交从FFPE样品中分离细胞。我们的研究将建立在我们强大的 初步数据，预计将提供证据，证明涉及的独特组合， 感染因子（EBV/HPV）。我们的发现将为预防和 针对这种恶性肿瘤更为常见的非洲人群进行筛查干预。