Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas

BLANCO, R; CARRILLO-BELTRÁN, D; MUÑOZ, JP; OSORIO, J; TAPIA, J; BURZIO, V; GALLEGOS, I; CALAF, G; PAOLA ANDREA CHABAY; AGUAYO, F

Microoganisms

mdpi

Lugar: Basilea; Año: 2022

2076-2607

Abstract: High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer.However, a low proportion of HR-HPV-infected women finally develop this cancer, which suggeststhe involvement of additional cofactors. Epstein?Barr virus (EBV) has been detected in cervicalsquamous cell carcinomas (SCCs) as well as in low- (LSIL) and high-grade (HSIL) squamous intraepitheliallesions, although its role is unknown. In this study, we characterized HR-HPV/EBVco-presence and viral gene expression in LSIL (n = 22), HSIL (n = 52), and SCC (n = 19) fromChilean women. Additionally, phenotypic changes were evaluated in cervical cancer cells ectopicallyexpressing BamHI-A Rightward Frame 1 (BARF1). BARF1 is a lytic gene also expressed in EBVpositiveepithelial tumors during the EBV latency program. HPV was detected in 6/22 (27.3%) LSIL,38/52 (73.1%) HSIL, and 15/19 (78.9%) SCC cases (p < 0.001). On the other hand, EBV was detectedin 16/22 (72.7%) LSIL, 27/52 (51.9%) HSIL, and 13/19 (68.4%) SCC cases (p = 0.177). HR-HPV/EBVco-presence was detected in 3/22 (13.6%) LSIL, 17/52 (32.7%) HSIL, and 11/19 (57.9%) SCC cases(p = 0.020). Additionally, BARF1 transcripts were detected in 37/55 (67.3%) of EBV positive cases andin 19/30 (63.3%) of HR-HPV/EBV positive cases. Increased proliferation, migration, and epithelialmesenchymaltransition (EMT) was observed in cervical cancer cells expressing BARF1. Thus, bothEBV and BARF1 transcripts are detected in low- and high-grade cervical lesions as well as in cervicalcarcinomas. In addition, BARF1 can modulate the tumor behavior in cervical cancer cells, suggestinga role in increasing tumor aggressiveness.