title: HPV-16 E2 physical status and molecular evolution in vivo in cervical carcinomas.
abstract: A key event in the development of cervical carcinoma is the deregulated expression of high-risk human papillomavirus (HR-HPV) oncogenes, most commonly due to HPV integration into host DNA. Here we explored whether HPV-16 E2 gene integrity is a biomarker of progressive disease with oncogenes expression. HPV-16 genome disruption was assessed by amplification of the entire E2 gene, while mRNA expression patterns of the E1, E2, E6, and E7 genes were evaluated by reverse transcription PCR (RT-PCR). As expected, E2 disruption was significantly higher among patients with cervical cancers than subjects with benign lesions (p=0.02). The status of the E2 gene correlated with tumorogenesis, and seemed also to correlate with the stage of the carcinomas, since integrated HPV-16 DNA was frequently detected in patients with advanced cancer stages (75% of stage III vs 60% stages I and II). In bivariate analysis, the lesions&rsquo; grade was most significantly associated with HPV-16 DNA disruption (p&lt;0.05). In cervical carcinoma the deletion pattern involved more frequently the E2 gene rather than the E1 gene (62.5% vs 45.8%). The prevalence of the E6/E7 HPV-16 transcripts in cervical carcinoma specimens and in benign cervical lesions were detected with frequencies of, respectively, 91.6% and 45.4%. The mRNA levels of the HPV-16 E6/E7 genes were expressed at approximately the same levels in each physical state. We consistently observed that E6/E7 were absent or weakly detectable in the presence of E2. However, in the absence of E2 the levels of E6/E7 markedly increased (p&lt;0.05). This study underscores the significance of investigating alternative mechanisms of E2 expression and oncogenes E6/E7 transcripts in vivo as biomarkers for disease severity in cervical carcinomas.
authors.affiliation: Unit of Immunology Microbiology Environmental and Carcinogenesis (IMEC), Science Faculty of Bizerte, University of Carthage, 7021 Jarzouna, Bizerte - Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Kahla
authors.forename: Lotfi
authors.initials: L
authors.lastname: Kochbati
authors.forename: Mohamed Badis
authors.initials: MB
authors.lastname: Chanoufi
authors.forename: Mongi
authors.initials: M
authors.lastname: Maalej
authors.forename: Ridha
authors.initials: R
authors.lastname: Oueslati
mesh_terms: D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16