PAX1/SOX1 gene methylation as a detection and triage method for triage of high risk HPV-Positive women in cervical cancer screening

IF 1.3 Q3 OBSTETRICS & GYNECOLOGY

Gynecologic Oncology Reports Pub Date : 2025-06-30 DOI:10.1016/j.gore.2025.101794

Ruyi Zhang , Ye Li , Yu Han , Chang Guo , Jie Guo , Jie Sun , Dengfeng Wang , Xiatao Hu , Jiao Li , Xuanying Zhao , Yiyuan Zhou , Tingting Zhai , Yuqiong Meng , Jing Wang , Wengao Chen

{"title":"PAX1/SOX1 gene methylation as a detection and triage method for triage of high risk HPV-Positive women in cervical cancer screening","authors":"Ruyi Zhang , Ye Li , Yu Han , Chang Guo , Jie Guo , Jie Sun , Dengfeng Wang , Xiatao Hu , Jiao Li , Xuanying Zhao , Yiyuan Zhou , Tingting Zhai , Yuqiong Meng , Jing Wang , Wengao Chen","doi":"10.1016/j.gore.2025.101794","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the role of PAX1/SOX1 methylation testing in the triage of HPV-positive patients and compare its performance with traditional screening methods, including HPV genotyping and cytology.</div></div><div><h3>Methods</h3><div>A study was conducted from February 2024 to October 2024, involving women referred for colposcopy during the “two-cancer screening” in a specific region. Patients were grouped based on histopathological results [normal/cervicitis, cervical intraepithelial neoplasia 1 (CIN1), high-grade squamous intraepithelial lesion (HSIL), cervical cancer] and high-risk human papillomavirus (hrHPV) typing (HPV16/18 positive, other 12 hrHPV positive). Cervical exfoliated cell specimens were collected for PAX1/SOX1 methylation and liquid-based cytology testing. Methylation status was detected using a specific PCR-fluorescence probe kit, and cytology results were interpreted according to the 2022 Bethesda System (TBS) system.</div></div><div><h3>Results</h3><div>The study included 640 participants. The mean Ct values of PAX1 and SOX1 decreased with the progression of cervical lesions. In the detection of high grad CIN+ (HG-CIN + ) in HPV-positive women, PAX1/SOX1 methylation testing showed higher AUCs (PAX1: 0.84; SOX1: 0.83) compared to HPV genotyping and cytology. For non-16/18 hrHPV positive cases, methylation testing had a better balance of sensitivity and specificity in detecting ≥ CIN2 and ≥ CIN3 lesions. Methylation testing also had the potential to reduce unnecessary colposcopy referrals in HPV-positive patients with cytology.</div></div><div><h3>Conclusions</h3><div>PAX1/SOX1 methylation testing shows potential as an effective adjunct to traditional cervical cancer screening methods. It can better identify high-grade lesions in HPV-positive patients and may reduce unnecessary referrals. However, larger-scale studies and long-term follow-up are needed to confirm its efficacy and optimize its integration into routine screening protocols.</div></div>","PeriodicalId":12873,"journal":{"name":"Gynecologic Oncology Reports","volume":"60 ","pages":"Article 101794"},"PeriodicalIF":1.3000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic Oncology Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352578925001195","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

To evaluate the role of PAX1/SOX1 methylation testing in the triage of HPV-positive patients and compare its performance with traditional screening methods, including HPV genotyping and cytology.

Methods

A study was conducted from February 2024 to October 2024, involving women referred for colposcopy during the “two-cancer screening” in a specific region. Patients were grouped based on histopathological results [normal/cervicitis, cervical intraepithelial neoplasia 1 (CIN1), high-grade squamous intraepithelial lesion (HSIL), cervical cancer] and high-risk human papillomavirus (hrHPV) typing (HPV16/18 positive, other 12 hrHPV positive). Cervical exfoliated cell specimens were collected for PAX1/SOX1 methylation and liquid-based cytology testing. Methylation status was detected using a specific PCR-fluorescence probe kit, and cytology results were interpreted according to the 2022 Bethesda System (TBS) system.

Results

The study included 640 participants. The mean Ct values of PAX1 and SOX1 decreased with the progression of cervical lesions. In the detection of high grad CIN+ (HG-CIN + ) in HPV-positive women, PAX1/SOX1 methylation testing showed higher AUCs (PAX1: 0.84; SOX1: 0.83) compared to HPV genotyping and cytology. For non-16/18 hrHPV positive cases, methylation testing had a better balance of sensitivity and specificity in detecting ≥ CIN2 and ≥ CIN3 lesions. Methylation testing also had the potential to reduce unnecessary colposcopy referrals in HPV-positive patients with cytology.

Conclusions

PAX1/SOX1 methylation testing shows potential as an effective adjunct to traditional cervical cancer screening methods. It can better identify high-grade lesions in HPV-positive patients and may reduce unnecessary referrals. However, larger-scale studies and long-term follow-up are needed to confirm its efficacy and optimize its integration into routine screening protocols.

查看原文本刊更多论文

PAX1/SOX1基因甲基化作为宫颈癌筛查中hpv阳性高危妇女分诊的检测和分诊方法

目的评价PAX1/SOX1甲基化检测在HPV阳性患者分诊中的作用，并与HPV基因分型和细胞学检测等传统筛查方法进行比较。方法研究于2024年2月至2024年10月进行，涉及特定地区在“双癌筛查”期间转诊进行阴道镜检查的女性。根据组织病理学结果[正常/宫颈炎、宫颈上皮内瘤变1型（CIN1）、高度鳞状上皮内病变（HSIL）、宫颈癌]和高危人乳头瘤病毒（hrHPV）分型（HPV16/18阳性，其余12例hrHPV阳性）对患者进行分组。收集宫颈脱落细胞标本进行PAX1/SOX1甲基化和液基细胞学检测。使用特异性pcr荧光探针试剂盒检测甲基化状态，细胞学结果根据2022 Bethesda系统（TBS）系统进行解释。结果该研究包括640名参与者。PAX1和SOX1的平均Ct值随着宫颈病变的进展而降低。在hpv阳性女性中，PAX1/SOX1甲基化检测显示较高的auc (PAX1: 0.84；SOX1: 0.83)与HPV基因分型和细胞学相比较。对于非16/18 hrHPV阳性病例，甲基化检测在检测≥CIN2和≥CIN3病变方面具有更好的敏感性和特异性平衡。甲基化检测也有可能减少hpv阳性细胞学患者不必要的阴道镜转诊。结论spax1 /SOX1甲基化检测可作为传统宫颈癌筛查方法的有效辅助手段。它可以更好地识别hpv阳性患者的高级别病变，并可能减少不必要的转诊。然而，需要更大规模的研究和长期随访来证实其有效性并优化其与常规筛查方案的整合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gynecologic Oncology Reports OBSTETRICS & GYNECOLOGY-

CiteScore

2.00

自引率

0.00%

发文量

183

审稿时长

41 days

期刊介绍： Gynecologic Oncology Reports is an online-only, open access journal devoted to the rapid publication of narrative review articles, survey articles, case reports, case series, letters to the editor regarding previously published manuscripts and other short communications in the field of gynecologic oncology. The journal will consider papers that concern tumors of the female reproductive tract, with originality, quality, and clarity the chief criteria of acceptance.