Abstract
BackgroundDespite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood.MethodsFifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively.ResultsHR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively.ConclusionThe high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation.
Highlights
Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood
HPV infections in the cervix are frequently associated with intraepithelial neoplasia and invasive squamous cell carcinomas (SCC) with all their different histological variants
In terms of co-infection, there was no significant difference between NC and Cervical intraepithelial neoplasia (CIN)-1 groups
Summary
Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood. The association between human papilomavirus (HPV) and cervical neoplasia is well documented [1]. HPV infections in the cervix are frequently associated with intraepithelial neoplasia and invasive squamous cell carcinomas (SCC) with all their different histological variants (large-cell keratinizing, large-cell nonkeratinizing and small-cell carcinoma). The long period of time (years) it takes for the development of cervical cancer after HPV infection suggests the involvement of other etiologies (such as viruses or cell compounds) in malignancy process. EpsteinBarr virus (EBV), ubiquitous human gamma-herpes virus responsible for mononucleosis [5], could be one of the ‘helper’ viruses. It can be sexually transmitted [5] and replicates in cervix cells [6]. EBV infection, widely spread among the population [7,8], has been associated with an increasing number of lymphocytic and epithelial cancers, mainly Burkitt’s lymphoma, Hodgkin’s lymphoma, T cell lymphoma, nasopharyngeal carcinoma (NPC) and gastric adenocarcinoma [9,10]
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