Epstein-Barr Virus DNA Is Associated With Conjunctival Squamous Cell Carcinomas: A Case-Control Study From Zimbabwe

Abstract

Incidence of conjunctival-squamous-cell-carcinoma (cSCC) in Zimbabwe is >30-fold higher than the global average. cSCC risk is notably higher among people living with Human Immunodeficiency Virus (HIV), implicating impaired immune response and a yet unknown infectious etiology. Formalin-fixed-paraffin-embedded blocks from Zimbabwe, comprising of conjunctival pre-cancer (n=78), invasive cSCC cases (n=148), and non-malignant eye lesions (n=119) were tested for multiple DNA viruses using Luminex bead-based-technology. Epstein-Barr virus (EBV) type 1 positivity was strongly associated with cSCC diagnosis (aOR 5.6; 95% CI 3.0-10.4) and marginally associated with pre-cancer (aOR 2.1; 95% CI 1.0-4.5). On analyzing EBV transcriptional activity with any of the three; LMP1, EBNA1, and BZLF1, RNA transcripts were detected in 5/112 controls, 3/67 precancers and 10/139 cases and none were associated with conjunctival case status. Our EBV DNA data suggests that EBV may play a role in conjunctival squamous cell carcinogenesis. However, low detection rates of EBV RNA, supports further investigation to infer causality.