Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

Shi-Rong Li,Fu-Guo Jiang,Zhen-Ming Wang,Yu-Hui Wang,Xi-Bo Wang,Jian-Qiang Zhao,Hai-Bin Xue

doi:10.7314/apjcp.2015.16.14.5843

Abstract

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Highlights

Optimal treatment option for women with atypical squamous cells of undetermined significance (ASCUS) is not well established
The paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) demonstrated a better performance than the high-risk human papillomavirus (HPV)-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases
Patient samples A total of 463 consecutive patients who participated in the cervical cytological screening by Thinprep cytologic test (TCT) technique in the Weifang city people’s hospital from January 2013 to December 2014, and with an ASCUS diagnosis based on the cytological screening, were selected

Summary

Introduction

Optimal treatment option for women with ASCUS is not well established. Most low-grade lesions regress spontaneously. In almost every invasive cervical cancer patient, HPV can be recognized (Park et al, 1996; Wang et al, 2013; Siriaunkgul et al, 2014). HR-HPV testing has been widely used for the triage of ASCUS patients (Wentzensen et al, 2010). HR-HPV testing has a good sensitivity , but the high prevalence of transient human papillomavirus infections limits it’s specificity (Dehn et al, 2007). Methylationsensitive high-resolution melting (MS-HRM) analysis has been introduced as a sensitive and rapid technique for the quantification of DNA methylation (Wu et al, 2011; Dimitrakopoulos et al, 2012). We tested the efficacy of PAX1 methylation analysis by MS-HRM for the triage of patients with ASCUS, and compared its performance with HRHPV testing

Materials and Methods

Findings

Discussion