Marcos Antonio Pereira de Lima

Epstein-barr virus (EBV) in cervical carcinoma detected by in situ hybridization targeting ebers and the viral genome

Epstein-Barr virus (EBV) infection has been suggested as a potential cofactor for the development and progression of cervical cancer, collaborating with high-risk Human Papillomavirus (HR-HPV). In situ hybridization (ISH) has been considered the gold standard in the investigation of EBV in neoplasms. This study aimed to detect EBV in cervical carcinoma samples using ISH targeting EBERs (EBER-ISH) and the BamHI-W region of the viral genome (BamHI-W-ISH), and compare the results of both targets. Of the 88 cases collected, 9 were EBER-ISH positive (10.2%), while 33 (37.5%) cases were positive for EBV by BamHI-W-ISH, all showing staining in the nuclei of the malignant cells. No statistically significant results were found between the presence of EBV and carcinoma type, differentiation grade or tumor staging. The kappa agreement index between the two targets was 0.092. Only 4 cases were EBER-ISH(+) and BamHI-W-ISH(-). On the other hand, 28 cases were BamHI-W-ISH(+) and EBER-ISH(-). Altogether, 37/88 (42%) cases were EBV-positive by one or both targets. Infected lymphocytes were verified in 9 (10.2%) and 34 (38.6%) cases, by EBER-ISH and BamHI-W-ISH, respectively. The slight agreement demonstrated between the targets may be due to the lack of expression of EBERs, suggesting that EBV may present a distinct latency pattern in the cervical mucosa, or that it has entered the replicative cycle in some of these tumors, in both cases, explaining the low positivity rate verified through EBER-ISH, while calling into question the latter's gold standard status in the detection of EBV in malignancies. Our findings also indicate that the chosen viral genomic target may represent a suitable candidate for EBV detection by ISH.