The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive

ObjectiveThis study aims to systematically evaluate the application value of PAX1 gene methylation detection in cervical lesion screening and its potential advantages in the triage of non-16/18 high-risk human papillomavirus (HR-HPV) positive patients.Materials and methodsThis study enrolled 1,619 H...

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Main Authors: Meng-Meng Chen, Bing-Qiang Zhang, Yan-Song Luan, Guo-Long Sun, Yun-Yuan Zhang, Xiao-Yan Zhou, Xi-Feng Zhang, Feng-Chun Gao, Jun-Mei Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1634297/full
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author Meng-Meng Chen
Meng-Meng Chen
Bing-Qiang Zhang
Bing-Qiang Zhang
Yan-Song Luan
Guo-Long Sun
Yun-Yuan Zhang
Xiao-Yan Zhou
Xi-Feng Zhang
Feng-Chun Gao
Jun-Mei Yu
author_facet Meng-Meng Chen
Meng-Meng Chen
Bing-Qiang Zhang
Bing-Qiang Zhang
Yan-Song Luan
Guo-Long Sun
Yun-Yuan Zhang
Xiao-Yan Zhou
Xi-Feng Zhang
Feng-Chun Gao
Jun-Mei Yu
author_sort Meng-Meng Chen
collection DOAJ
description ObjectiveThis study aims to systematically evaluate the application value of PAX1 gene methylation detection in cervical lesion screening and its potential advantages in the triage of non-16/18 high-risk human papillomavirus (HR-HPV) positive patients.Materials and methodsThis study enrolled 1,619 HPV-positive female patients who visited the Affiliated Hospital of Qingdao University from December 2023 to March 2025, with 989 patients ultimately meeting the inclusion criteria. All subjects underwent HPV-DNA testing, cytological examination, colposcopy, and PAX1 gene methylation detection, with results analyzed in conjunction with histopathological evaluations. HPV-DNA detection was performed using fluorescence quantitative PCR methodology capable of identifying 17 high-risk HPV genotypes. Cytological examination results were classified according to the International Society of Cytology standards. PAX1 gene methylation detection employed fluorescence quantitative PCR technology with ACTB as the internal reference gene, determining methylation levels through calculation of ΔCT values. Statistical analyses included ROC curve assessment of diagnostic performance, with intergroup comparisons conducted using one-way analysis of variance and Pearson’s chi-squared test.ResultsThe results demonstrated that PAX1 gene methylation detection showed significantly better diagnostic performance compared to cytological examination for the detection of CIN2+ and CIN3+ lesions. The AUC values for PAX1 gene methylation detection in diagnosing CIN2+and CIN3+ were 0.934 (95% confidence interval [CI]: 0.916–0.948) with sensitivity of 93.49% and specificity of 93.24%and0.875 (95% confidence interval [CI]: 0.853–0.895)with sensitivity of 95.31% and specificity of 79.77%. Among non-16/18 HR-HPV(in women positive for high-risk HPV types other than 16/18) positive patients, PAX1 gene methylation detection demonstrated higher sensitivity and specificity than cytological examination, enabling more accurate identification of patients requiring further intervention and reducing unnecessary colposcopy referrals. Furthermore, in HR-HPV positive patients with cytology results ≤ASCUS, PAX1 gene methylation detection significantly decreased colposcopy referral rates (22.29%), thus alleviating patients’ medical burden.ConclusionPAX1 gene methylation detection exhibits strong diagnostic efficiency for cervical lesions and holds significant value in triage diagnosis of non-16/18 HR-HPV positive.
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spelling doaj-art-b5a2df52c0a34d6b9b9cd394e48d64d52025-07-24T04:10:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16342971634297The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positiveMeng-Meng Chen0Meng-Meng Chen1Bing-Qiang Zhang2Bing-Qiang Zhang3Yan-Song Luan4Guo-Long Sun5Yun-Yuan Zhang6Xiao-Yan Zhou7Xi-Feng Zhang8Feng-Chun Gao9Jun-Mei Yu10Qingdao Restore Medical Laboratory Co., Ltd., Qingdao, Shandong, ChinaKey Laboratory of Cancer and Immune Cells of Qingdao, Qingdao, ChinaQingdao Restore Medical Laboratory Co., Ltd., Qingdao, Shandong, ChinaKey Laboratory of Cancer and Immune Cells of Qingdao, Qingdao, ChinaQingdao Restore Medical Laboratory Co., Ltd., Qingdao, Shandong, ChinaQingdao Restore Medical Laboratory Co., Ltd., Qingdao, Shandong, ChinaDepartment of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaCollege of Veterinary Medicine, Qingdao Agricultural University, Qingdao, ChinaDepartment of Obstetrics, Jinan Materlity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, ChinaQingdao Restore Medical Laboratory Co., Ltd., Qingdao, Shandong, ChinaObjectiveThis study aims to systematically evaluate the application value of PAX1 gene methylation detection in cervical lesion screening and its potential advantages in the triage of non-16/18 high-risk human papillomavirus (HR-HPV) positive patients.Materials and methodsThis study enrolled 1,619 HPV-positive female patients who visited the Affiliated Hospital of Qingdao University from December 2023 to March 2025, with 989 patients ultimately meeting the inclusion criteria. All subjects underwent HPV-DNA testing, cytological examination, colposcopy, and PAX1 gene methylation detection, with results analyzed in conjunction with histopathological evaluations. HPV-DNA detection was performed using fluorescence quantitative PCR methodology capable of identifying 17 high-risk HPV genotypes. Cytological examination results were classified according to the International Society of Cytology standards. PAX1 gene methylation detection employed fluorescence quantitative PCR technology with ACTB as the internal reference gene, determining methylation levels through calculation of ΔCT values. Statistical analyses included ROC curve assessment of diagnostic performance, with intergroup comparisons conducted using one-way analysis of variance and Pearson’s chi-squared test.ResultsThe results demonstrated that PAX1 gene methylation detection showed significantly better diagnostic performance compared to cytological examination for the detection of CIN2+ and CIN3+ lesions. The AUC values for PAX1 gene methylation detection in diagnosing CIN2+and CIN3+ were 0.934 (95% confidence interval [CI]: 0.916–0.948) with sensitivity of 93.49% and specificity of 93.24%and0.875 (95% confidence interval [CI]: 0.853–0.895)with sensitivity of 95.31% and specificity of 79.77%. Among non-16/18 HR-HPV(in women positive for high-risk HPV types other than 16/18) positive patients, PAX1 gene methylation detection demonstrated higher sensitivity and specificity than cytological examination, enabling more accurate identification of patients requiring further intervention and reducing unnecessary colposcopy referrals. Furthermore, in HR-HPV positive patients with cytology results ≤ASCUS, PAX1 gene methylation detection significantly decreased colposcopy referral rates (22.29%), thus alleviating patients’ medical burden.ConclusionPAX1 gene methylation detection exhibits strong diagnostic efficiency for cervical lesions and holds significant value in triage diagnosis of non-16/18 HR-HPV positive.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1634297/fullcervical cancermethylationPAX1HR-HPVTCT
spellingShingle Meng-Meng Chen
Meng-Meng Chen
Bing-Qiang Zhang
Bing-Qiang Zhang
Yan-Song Luan
Guo-Long Sun
Yun-Yuan Zhang
Xiao-Yan Zhou
Xi-Feng Zhang
Feng-Chun Gao
Jun-Mei Yu
The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
Frontiers in Immunology
cervical cancer
methylation
PAX1
HR-HPV
TCT
title The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
title_full The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
title_fullStr The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
title_full_unstemmed The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
title_short The diagnostic of PAX1 gene methylation in cervical lesions and its role in the triage of non-16/18 HR-HPV positive
title_sort diagnostic of pax1 gene methylation in cervical lesions and its role in the triage of non 16 18 hr hpv positive
topic cervical cancer
methylation
PAX1
HR-HPV
TCT
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1634297/full
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