CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions

Abstract

<b>Background:</b> From our previous study, we established that cyclin A1 (CCNA1) promoter methylation isstrongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as adiagnostic maker of disease. <br/><b>Objectives</b>: The purpose of the present study was to assess the prevalence of CCNA1promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNAscreening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters likesensitivity, specificity, predictive values and likelihood ratio. <br/><b>Methods</b>: In this retrospective study, histopathologywas used as the gold standard method with specimens separated into the following groups: negative (n=31), lowgradesquamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse(HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation wasexamined by CCNA1 duplex methylation specific PCR. <br/><b>Results</b>: The results showed the frequencies of CCNA1promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequencyin all three groups, it could not differentiate between the different groups and grades of precancerous lesions. Incontrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levelsof all statistic parameters. <br/><b>Conclusion</b>: CCNA1 promoter methylation is a potential marker for distinguishingbetween histologic negative/LSIL and HSIL+using cervical cytology samples.