The objective of current study was to determine the p16INK4a mRNA level in cervical cells by relative quantification (RQ) and to test viral E6 expression in human papillomavirus (HPV) -16 or -18–positive specimens by widely used methods. We targeted the pivotal mRNA level associated with severe dysplasia or worse.
Cervical specimens were taken from 134 women with cervical disease and 132 women with normal cytologic results. The presence of HPV was analyzed by sequencing. The results of p16INK4a and E6 analyses were statistically processed in receiver operating characteristic curve analysis to predict severe dysplasia or worse.
The HPV DNA was detected in 81.4% (109/134) of women with cervical disease and in 27.3% (36/132) of women with normal cytologic results. HPV-16 or -18 were present in 59.7% (80/134) of abnormal specimens. p16INK4a and E6 mRNA expression was increasing with severity of cervical dysplasia. p16INK4a mRNA expression was found 4.35-fold and 13.15-fold increased in high-grade squamous intraepithelial lesions and squamous cell carcinomas, respectively. E6 mRNA expression was significantly increased (p = .0038) in severe dysplasias or worse. The RQ method achieved better sensitivity (82.6%), and E6 mRNA got better specificity (80.6%) for the prediction of severe dysplasia or worse.
An increasing level of p16INK4a and E6 mRNA transcripts could mean the potential of cervical dysplasia progression to cancer, but further studies should be done to confirm this proposition. Nevertheless, we consider using both tests to improve the sensitivity and specificity for prediction of severe dysplasia or worse.
Tests for E6 mRNA expression and relative quantification of p16INK4a should improve sensitivity and specificity for prediction of severe dysplasia or worse.
Departments of 1Obstetrics and Gynecology and 2Molecular Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic
Reprint requests to: Veronika Janusicova, MSc, PhD, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Kollarova 2, 036 01 Martin, Slovak Republic. E-mail: firstname.lastname@example.org
The authors have no conflicts of interests to declare.
This study was supported in part by grants UK/71/2010 and UK/103/2011 from the Ministry of Education and by “Molecular diagnosis of cervical cancer” ITMS code 26220220113 project co financed from EU funds.