Human Papillomaviruses and Epstein–Barr Virus Interactions in Colorectal Cancer: A Brief Review

Abstract

Human papillomaviruses (HPVs) and the Epstein–Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%–15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis.

High-Risk Human Papillomaviruses and Epstein–Barr Virus in Colorectal Cancer and Their Association with Clinicopathological Status

“…The combined oncogenic effects of viral infections have been recognized as potential oncogenic drivers in various cancers [ 6 ]. Oncoviruses can lead to the onset and progression of cancer via commonly shared pathways including WNT/β-catenin, JAK/STAT/SRC, PI3k/Akt/mTOR, and/or RAS/MEK/ERK signaling pathways [ 6 , 8 , 14 , 41 ]. A study conducted by Guidry and Scott [ 63 ] showed that co-infection by HPV and EBV enhances EBV persistence either via latency or increased viral replication or by aggregating HPV oncogene expression.…”

“…Among viral factors, microbial–epithelial interactions are assumed to instigate oncogenic activity, which could lead to the onset and development of CRC [ 3 ]. Viral infections by high-risk human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) have been linked with the initiation and progression of several human carcinomas [ 4 , 5 , 6 ].…”

Establishment of a Patient-Derived Xenograft Model of Colorectal Cancer in CIEA NOG Mice and Exploring Smartfish Liquid Diet as a Source of Omega-3 Fatty Acids

“…Hence the EBV was likely latent in lymphoid cells in the tumor, but at a very low level since it was not detected by EBER ISH in the patient samples. EBV is known as an oncovirus and is found latent in more than 90% of humans (reviewed in [ 32 ]). These rapidly growing lymphomas resulted in reduced time for the xenografts to establish due to increased tumor burden and/or reduced general health of the affected animals, as found in the study by Chjiwa et al [ 21 ].…”

Study of Epstein - Barr virus Infection in Relation to the Immunohistochemical Expression of Bcl-2 gene in Tissues of Patients with Adenocarcinoma of the Colon

“…During EBV latent infection enhances the oncogenic properties via compromising immune system and enhancing chronic inflammatory microenvironment. This virus encodes 6 viral nuclear antigens (EBNA-1, -2, -3A, -3B, -3C and LP), 3 viral latent membrane proteins (LMP-1, -2A and -2B), 2 small viral non-coding Ribonucleic acids (EBER-1 and -2) and rightward transcripts of BamHI-A, where the main function of these proteins is to evade immune surveillance and to play as "oncogenes" in EBV -infected cells, by silencing the anti-EBV effect of INF-γ and modulating anti-viral cytokines (TNF-α, IL-1β and IL-6 ) and mimicking the IL-10 characteristics (23,24) . Bcl-2 is well documented as a key inhibitor of apoptosis that play a major role to maintain normal balance between both apoptosis and cellular survival.…”