Epstein–Barr Virus, but not human Papillomavirus, is associated with preinvasive and invasive ocular surface squamous neoplasias in Zambian patients

• Autores: Julius, Peter; Siyumbwa, Stepfanie N.; Moonga, Phyllis; Maate, Fred; Kaile, Trevor; Haynatski, Gleb; Minhas, Veenu; Snow, Jazmine; Peterson, Kerstin; Gihozo, Patience; Streeter, Sam; Kaur, Salan; Evans, Annika; Gonzalez, Daniela del Carmen; Samwel, Kandali; Kang, Guobin; West, John T.; Wood, Charles; Angeletti, Peter C.
• Año de publicación: 2022
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: OCULAR SURFACE SQUAMOUS NEOPLASIA; HUMAN PAPILLOMA VIRUS; EPSTEIN-BARR VIRUS; ZAMBIA; HUMAN IMMUNODEFICIENCY VIRUS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Background: The etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020. Methods: Demographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi’s sarcomaassociated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis. Results: OSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [corneaconjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN. Conclusions: Our findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study.
Fil: Julius, Peter. School of Medicine. Department of Pathology and Microbiology; Zambia
Fil: Siyumbwa, Stepfanie N.. School of Medicine. Department of Pathology and Microbiology; Zambia
Fil: Moonga, Phyllis. University Teaching Hospital; Zambia
Fil: Maate, Fred. School of Medicine. Department of Pathology and Microbiology; Zambia
Fil: Kaile, Trevor. School of Medicine. Department of Pathology and Microbiology; Zambia
Fil: Haynatski, Gleb. University of Nebraska Medical Center. Department of Biostatistics; Estados Unidos
Fil: Minhas, Veenu. University of Nebraska Medical Center. Department of Biostatistics; Estados Unidos
Fil: Snow, Jazmine. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Peterson, Kerstin. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Gihozo, Patience. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Streeter, Sam. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Kaur, Salan. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Evans, Annika. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Gonzalez, Daniela del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad de Nebraska - Lincoln; Estados Unidos
Fil: Samwel, Kandali. Ocean Road Cancer Institute; Tanzania
Fil: Kang, Guobin. Louisiana State University Health Science Center; Estados Unidos
Fil: West, John T.. Louisiana State University Health Science Center; Estados Unidos
Fil: Wood, Charles. Louisiana State University Health Science Center; Estados Unidos
Fil: Angeletti, Peter C.. Universidad de Nebraska - Lincoln; Estados Unidos