Prediction of Human Papillomavirus 16 E6 Gene Expression and Cervical Intraepithelial Neoplasia Progression by Methylation Status. Issue 3 (1st March 2009)

• Record Type: Journal Article
• Authors: Hublarova, Pavla; Hrstka, Roman; Rotterova, Pavla; Rotter, Leopold; Coupkova, Marie; Badal, Vinay; Nenutil, Rudolf; Vojtesek, Borivoj
• Is Part Of: International journal of gynecological cancer. Volume 19:Issue 3(2009)
• Page Start: 321
• Page End: 325
• Publication Date: 2009-03-01
• Subjects: Cervix -- Cervical intraepithelial neoplasia -- HPV-16 -- E6 gene -- Promoter methylation; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1111/IGC.0b013e31819d8a5c
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Introduction: Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. We aimed to analyze the consequences of methylation of the E6 gene promoter in distinct stages of HPV-16-induced cellular transformation to assess its importance for disease progression. Methods: Human papillomavirus 16 was detected by sensitive polymerase chain reaction (PCR). Determination of E6 gene promoter methylation was analyzed by digestion with specific restriction endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was determined by quantitative real-time PCR. Results: Of 103 cervical smears from asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix carcinoma specimens. The incidence of HPV-16 in all lesions compared with asymptomatic women was statistically significant ( P < 0.001, Pearson χ 2 test). Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n = 23) in carcinomas; a statistical significance between lesions and healthy women was found ( P < 0.001, Pearson χ 2 test). Expression of E6 mRNA correlated with methylation status ( P = 0.010, Mann-Whitney U test). Conclusions: We conclude that methylation of the E6 gene promoter in HPV-16 genome is a predictive biomarker for cervical cancer progression by regulating the expression of the E6 oncogene.