PAX1 Methylation Analysis by MS-HRM is Useful in Triage of High-grade Squamous Intraepithelial Lesions

Zhen-Ming Wang

doi:10.7314/apjcp.2014.15.2.891

Abstract

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

Highlights

Optimal treatment option for women with atypical squamous cells -cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) is not well established
This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylationsensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test
The HC2 high-risk HPV (HR-HPV) test result was positive in 100% of the cervical carcinoma, 66.7% of the CIN3 and 64.7% of CIN2 specimens

Summary

Introduction

Optimal treatment option for women with atypical squamous cells -cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) is not well established. A small but significant proportion of cases with ASC-H may harbour cervical intraepithelial neoplasia (CIN), or even invasive carcinoma. ASC-H smears need further investigation to identify patients likely to have a high-grade lesion. In almost every case of invasive cervical cancer and its pre-malignant progenitors, HPV can be recognized (Walboomers et al, 1999; Nambaru et al, 2009; Wang et al, 2013). HPV testing has been adopted for the triage of patients with ASC-H (Wu et al, 2006; Bandyopadhyay et al, 2008). In the older age group, HPV-DNA testing may be of benefit to better identify those women at risk for high grade lesions (Selvaggi , 2013). Methylation-sensitive high-resolution melting (MS-HRM) analysis has recently been introduced as a rapid and sensitive technique for the quantification of DNA methylation (Wu et al, 2011; Dimitrakopoulos et al, 2012)

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