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Review
. 2020 Aug 21;9(9):685.
doi: 10.3390/pathogens9090685.

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives

Rancés Blanco  1 , Diego Carrillo-Beltrán  1 , Julio C Osorio  2 , Gloria M Calaf  3   4 , Francisco Aguayo  5
Affiliations
Review

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives

Rancés Blanco et al. Pathogens. .

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.

Keywords: Epstein-Barr virus; cervical cancer; coinfection; human papillomavirus; tissue-infiltrating lymphocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Epstein-Barr virus (left) and human papillomavirus (right) genome organizations. Created by BioRender.com.
Figure 2
Figure 2
A model of carcinogenesis induced by high risk (HR)-HPV/EBV coinfection in the uterine cervix. HR-HPV infected cells are prone to latent EBV infection during neoplastic progression. Additionally, EBV infection of infiltrating lymphocytes cooperates with the immune escape of HPV-infected cells, modulating the host immune responses. Created by BioRender.com.
Figure 3
Figure 3
A hypothetical model of HR-HPV/EBV interaction in cervical epithelial cells. 1. HR-HPV infection and viral integration promotes DNA damage and genomic instability in cervical cells; 2. DNA damage promotes the establishment of EBV latency (I/II) with potential expression of some lytic genes such as BARF1 (abortive lytic expression); 3. BARF1 (and other viral oncogenes) promotes oncogenic changes and immune evasion, cooperating with HR-HPV. Created by BioRender.com.
See this image and copyright information in PMC

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