HPV-16 E2 Physical Status and Molecular Evolution in Vivo in Cervical Carcinomas

• Published in: The International journal of biological markers Vol. 29; no. 1; pp. e78 - e85
• Main Authors: Kahla, Saloua, Kochbati, Lotfi, Badis Chanoufi, Mohamed, Maalej, Mongi, Oueslati, Ridha
• Format: Journal Article
• Language: English
• Published: United States 24.03.2014
• Subjects: Adult; Aged; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Evolution, Molecular; Female; Gene Expression Regulation, Viral; Human papillomavirus 16 - genetics; Human papillomavirus 16 - pathogenicity; Humans; Middle Aged; Neoplasm Staging; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Papillomavirus E7 Proteins - biosynthesis; Polymerase Chain Reaction; Repressor Proteins - biosynthesis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0393-6155; 1724-6008; 1724-6008
• DOI: 10.5301/jbm.5000051

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’ grade was most significantly associated with HPV-16 DNA disruption (p<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<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.