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

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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.