CpG methylation of the PAX1 promoter in exfoliated cervical cells: a potential cervical cancer screening model

Cervical cancer screening is an effective mean of preventing cervical cancer, however, there are limitations of the current screening methods. In this study, an automated high throughput paired box-1 (PAX1) methylation detection method was designed by employing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which analyzed 88 PAX1 methylation sites. In total, 188 subjects were enrolled in the study. The diagnostic efficacy of various PAX1 methylation sites for detecting cervical intraepithelial neoplasia II or more severe lesions was analyzed and compared with current cervical cancer screening methods. A predictive model was constructed using logistic regression. Five sites with the largest area under receiver operating characteristic curve values were GRCh38/hg38, chr20: X21705687, X21705946, X21706427, X21706285 and X21706637. PAX1 methylation method had higher diagnostic efficacy than high risk human papillomavirus (hr-HPV) and ThinPrep cytology tests. A predictive model combining hr-HPV and PAX1 methylation sites was constructed as follows: prediction index = −5.993 + 15.211 × X21705687+ 7.890 × X21706427 + 1.846 × HPV16/18 (1,0) + 1.821 × other hr-HPV (1,0). Area under the curve was 0.868 and sensitivity and specificity were 0.863 and 0.756, respectively. Analysis of PAX1 promoter methylation alone or in combination with hr-HPV was a promising approach for cervical cancer screening. The study was registered in Chinese Clinical Trial Registry (registration number: ChiCTR2000029231, http://www.chictr.org.cn/index.aspx).

Cervical cancer screening; MALDI-TOF MS; Methylation; PAX1

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