Role of epstein‐barr virus and human papillomavirus coinfection in cervical cancer: Epidemiology, mechanisms and perspectives

Abstract

High‐risk human papillomavirus (HR‐HPV) is etiologically associated with the development and progression of cervical cancer, although other factors are involved. Epstein‐Barr virus (EBV) detection in premalignant and malignant tissues from uterine cervix has been widely reported; however, its contribution to cervical cancer development is still unclear. Here, a comprehensive analysis regarding EBV presence and its potential role in cervical cancer, the frequency of EBV/HR‐HPV coinfection in uterine cervix and EBV infection in tissue‐infiltrating lymphocytes were revised. Overall, reports suggest a potential link of EBV to the development of cervical carcinomas in two possible pathways: (1) Infecting epithelial cells, thus synergizing with HR‐HPV (direct pathway), and/or (2) infecting tissue‐infiltrating lymphocytes that could generate local immunosuppression (indirect pathway). In situ hybridization (ISH) and/or immunohistochemical methods are mandatory for discriminating the cell type infected by EBV. However, further studies are needed for a better understanding of the EBV/HR‐HPV coinfection role in cervical carcinogenesis.