Epstein-Barr Virus Latent Membrane Protein 1 Expression Identifies a Latency II-Consistent Subset of Oral Squamous Cell Carcinoma: A Case-Control Study from Najaf, Iraq

Abstract

Background & Objectives: Although Epstein-Barr virus (EBV) is firmly implicated in nasopharyngeal carcinoma, its role in oral squamous cell carcinoma (OSCC) remains contested. LMP1, the principal EBV oncoprotein, drives cellular transformation and blocks epithelial differentiation. We assessed LMP1 immunohistochemical expression and its concordance with EBER in an Iraqi OSCC cohort, and whether the pattern is consistent with a Latency II programme.

Methods: In a retrospective case-control study, 50 OSCC cases and 50 histologically normal oral mucosa controls from Najaf were examined. EBV was localised by chromogenic EBER in situ hybridisation; LMP1 was detected by immunohistochemistry (rabbit monoclonal clone D24-G, 1:100). Non-parametric tests were applied throughout, with Cohen's κ and McNemar's test for LMP1–EBER agreement.

Results: LMP1 was detected in 13/50 cases (26.0%) and no controls (Fisher's exact P = 0.0001; Haldane–Anscombe OR = 36.36), and moderate-to-strong expression predominated among positives (8/13). A non-significant trend toward higher positivity was seen in moderately differentiated tumours (Grade 2, 55.6%, vs 21.2% and 12.5%; H = 5.230, P = 0.073), with no association with sex (P = 0.746) or age (P = 0.303). All 13 LMP1-positive cases were EBER-positive, whereas 9 of 22 EBER-positive cases lacked LMP1 (κ = 0.618; McNemar P = 0.004).

Conclusion: Active, Latency II-consistent EBV signalling characterises a defined 26% subset of Iraqi OSCC (Stratum A, LMP1+/EBER+), alongside an 18% Latency 0/I-consistent subset (Stratum B, LMP1−/EBER+). This asymmetric concordance provides molecular evidence for coexisting latency programmes in oral carcinogenesis, although sub-threshold LMP1 expression cannot be excluded for Stratum B.