Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1)

Tai Kuang Chao, Feng Yi Ke, Yu Ping Liao, Hui Chen Wang, Cheng Ping Yu, Hung Cheng Lai

Research output: Contribution to journalArticle

26 Citations (Scopus)

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. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalDiagnostic Cytopathology
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

Fingerprint

Triage
DNA Methylation
Methylation
Genes
Atypical Squamous Cells of the Cervix
Case-Control Studies
Biopsy
Squamous Intraepithelial Lesions of the Cervix

Keywords

  • ASC-H
  • atypical squamous cells of undetermined significance (ASCUS)
  • cervix
  • epigenetics
  • methylation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1). / Chao, Tai Kuang; Ke, Feng Yi; Liao, Yu Ping; Wang, Hui Chen; Yu, Cheng Ping; Lai, Hung Cheng.

In: Diagnostic Cytopathology, Vol. 41, No. 1, 01.2013, p. 41-46.

Research output: Contribution to journalArticle

Chao, Tai Kuang ; Ke, Feng Yi ; Liao, Yu Ping ; Wang, Hui Chen ; Yu, Cheng Ping ; Lai, Hung Cheng. / Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1). In: Diagnostic Cytopathology. 2013 ; Vol. 41, No. 1. pp. 41-46.
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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. Diagn. Cytopathol. 2013. {\circledC} 2011 Wiley Periodicals, Inc.",
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