Human Papillomavirus and Epstein-Barr virus co-infection in Cervical Carcinoma in Algerian women

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.

First Report of Three Major Oncogenic Viruses: Human Papillomavirus, Epstein-Barr Virus And Merkel Cell Polyomavirus in Penile Cancer

“…EBV has been frequently found in the genital mucosa, urethral discharges and genital ulcers [19,20] and, as the cause of approximately 50% of human penile cancers is still unknown, some studies have proposed the role of EBV as a cofactor in HPV integration and induction of malignant transformation [21,22]. Although epigenetic alterations involving hipermethylation of tumor suppressor genes were proposed as additional co-factors favoring oncogenesis [23], we did not observe an altered pattern on p16 methylation status of the studied sample, suggesting that other oncogenic pathways are involved.…”

Virus and Cervical Cancer: Role and implication: A Review

“…The virus has early genes (E1 to E7) that encode proteins that regulate transcription, replication and maintenance and take an important role in the early phase of cervical carcinogenesis. The late capsid genes (L1 and L2) encode structural proteins that are required to form viral proteins and hence in replication of the virus (Abreu et al, 2012;Grce et al, 2004;Jones, 1995;Kahla et al, 2012;Khenchouche et al, 2013;NobelPrize, 2008;Villa and Denny, 2006). HPV infection is a sexually transmitted disease.…”

“…Women infected with EBV have threefold likelihood to develop cervical cancer. Still the role of EBV in cervical cancer is controversial and is a great debate (Kahla et al, 2012;Khenchouche et al, 2013). Another study showed HPV in 89% cases of cervical cancer and HPV with EBV in 68% cases (Prayitno, 2006).…”

“…Such cells are susceptible to other oncogenic stimuli and thus EBV has a role in malignant transformation (Khenchouche et al, 2013). In a study, EBV EBNA-1 was more prevalent in cervical cancer than in benign lesions and in positive cases of EBV there was a fivefold increase in risk of HPV 16 gene integration in the host genome.…”

“…Thus, EBV acts as a co-factor favouring integration of HPV DNA and thus induces cervical cancer. The other described mechanisms are, EBV-infected tumour show lymphocytic infiltration which produce viral IL10 expressed from BCRF-1 that decreases the local immunity and cause suppression of the response to HPV transformed cells; EBV contributes to the integration of HPV16 genome; EBV EBNA1 protein decreases apoptosis and DNA repair in EBVassociated lesions contributing to malignant transformation of co-transfected EBV/HPV lesions (Kahla et al, 2012;Khenchouche et al, 2013). EBV activates the growth-promoting pathway that are normally triggered by T cell-derived signal (Alibek et al, 2012).…”