Co-Incidence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women.

Hamda Al-Thawadi,Ala-Eddin Al Moustafa,Lina Ghabreau,Amber Yasmeen,Gerald Batist,Semir Vranic,Tahar Aboulkassim

doi:10.3389/fonc.2018.00250

Abstract

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Highlights

Cervical cancer is the fourth most common malignancy among women worldwide with approximately 528,000 new cases and 266,000 deaths each year estimated by the World Health Organization
We further investigated the co-presence of Epstein–Barr virus (EBV) and high-risk human papillomaviruses (HPVs) in our 44 samples by polymerase chain reaction (PCR) and IHC analysis using specific primers for LMP1 and EBNA1 as well as E6/E7 genes of EBV and HPVs, respectively (Table 1; Figure S1 in Supplementary Material) and monoclonal antibodies for LMP1 and E6, as described in the Section “Materials and Methods.”
We explored, for the first time, the co-presence of EBV and high-risk HPVs in human cervical cancer and the role of this co-incidence with cancer phenotype in the conventional Middle East region

Summary

Introduction

Cervical cancer is the fourth most common malignancy among women worldwide with approximately 528,000 new cases and 266,000 deaths each year estimated by the World Health Organization. Most cervical cancer deaths (87%) occur in the developing countries. It is well known that the majority of cancer deaths are the result of metastasis, either directly due to tumor involvement of critical organs or indirectly due to therapeutic resistance and the inability of available therapy to control tumor progression [1]. 20% of human cancers could be linked to oncoviruses infection including Epstein–Barr virus (EBV) and high-risk human papillomaviruses (HPVs) especially types 16, 18, and 33 [2,3,4]. Acute infection with EBV can cause infectious mononucleosis, and its latent state can lead to several types of human B-cell lymphomas and carcinomas, especially nasopharyngeal [5, 6]

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