title: Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1).
abstract: Detection of cervical high-grade squamous intraepithelial lesions (HSIL) in patients with equivocal cytological abnormalities, such as atypical squamous cells (ASC) of undetermined significance (ASCUS) or inability to exclude high-grade squamous intraepithelial lesions (ASC-H) is still a challenge. This study tested the efficacy of PAX1 methylation analysis in the triage of cervical ASCUS and ASC-H and compared its performance with Hybrid Capture 2 (HC2) HPV test. A hospital-based case-control study was conducted. Cervical scrapings from patients with ASCUS or ASC-H were used for the quantitative methylation analysis of PAX1 methylation by MethyLight and HPV testing by HC2. Patients with ASC-H or ASCUS with repeated abnormal smears underwent colposcopic biopsy and subsequent therapies. Diagnoses were made by histopathology at a follow-up of 2 years. The efficacies of detecting high-grade lesions were compared. Fifty-eight cervical scrapings with cytological diagnosis of ASCUS (n = 41) and ASC-H (n = 17) were analyzed. One of the 41 (2.4%) ASCUS patients and seven of 17 (41.2%) ASC-H patients were confirmed to have HSIL. After dichotomy of the PMR, PAX1 methylation rates were significantly higher in ASC developing HSIL compared with those developing reactive atypia (87.5% vs. 12.5%, P < 0.001). Testing PAX1 methylation in cervical swabs of patients with ASC confers better sensitivity (87.5% vs. 62.5%) and specificity (98.0% vs. 86.0%) than HC2 HPV testing. We show for the first time that PAX1 hypermethylation analysis may be a better choice than HC2 in the triage of ASCUS and ASC-H.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Tai-Kuang
authors.initials: TK
authors.lastname: Chao
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Ke
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Liao
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Wang
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
mesh_terms: D019175:DNA Methylation; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011230:Precancerous Conditions / Q000175:diagnosis*; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*
chemical_list: D051761:Paired Box Transcription Factors; C070835:PAX1 transcription factor