mRNA expression in cervical specimens for determination of severe dysplasia or worse in HPV-16/18-positive squamous lesions.
OBJECTIVE
The objective of current study was to determine the p16 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.


METHODS
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 p16 and E6 analyses were statistically processed in receiver operating characteristic curve analysis to predict severe dysplasia or worse.


RESULTS
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. p16 and E6 mRNA expression was increasing with severity of cervical dysplasia. p16 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.


CONCLUSIONS
An increasing level of p16 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.
Departments of 1Obstetrics and Gynecology and 2Molecular Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic.
Veronika
V
Janusicova
Andrea
A
Mendelova
Pavol
P
Zubor
Ivana
I
Kapustova
Iveta
I
Svecova
Erik
E
Kudela
Tatiana
T
Burjanivova
Zora
Z
Lasabova
Jan
J
Danko
D000293:Adolescent; D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics*; D030361:Papillomavirus Infections / Q000139:chemically induced* / Q000150:complications / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis*; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D055815:Young Adult
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins