Correlation between ebv co-infection and HPV16 genome integrity in Tunisian cervical cancer patients

Abstract

Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

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.…”

“…About 99% of invasive cervical cancer has been found to be HPV-positive. The peak age of invasive cervical cancer is 40-50 years of age (Grce et al, 2004;http://www.virology.uct.ac.za/teachhpv.html;Jean Anderson, 2012;Kahla et al, 2012;Ononogbu et al, 2013).…”

“…Inactivation of P53 protein causes decreased apoptosis, and that of Rb protein causes increased proliferation of cells. In addition, chronic cervicitis by HPV causes production reactive oxygen species and free radicals that cause oxidative stress followed by the negative impact on genetic and cellular processes (Jean Anderson, 2012;Jones, 1995;Kahla et al, 2012;Prayitno, 2006). The HPV cannot be cultured.…”

“…shows the sensitivity, specificity, positive predictive value and negative predictive value of some novel markers. The novel markers in HPV infection play a greater role in cervical cancer screening (Jin et al, 2013;Kahla et al, 2012;Villa and Denny, 2006). Anderson, 2012;Ononogbu et al, 2013;Sinayobye et al, 2014).…”

“…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).…”