Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients
Abstract Objective To assess the triage value of multigene methylation testing for cervical intraepithelial neoplasia 2 and above (CIN2+) in high-risk human papillomavirus (hrHPV) positive patients. Methods 634 hrHPV-positive cases were selected from the gynecology outpatient clinic at Hainan Women...
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BMC
2025-04-01
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| Series: | Infectious Agents and Cancer |
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| Online Access: | https://doi.org/10.1186/s13027-025-00652-4 |
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| author | Caiyun Lin Chenye Zhu Meihua Xie Hua Yang |
| author_facet | Caiyun Lin Chenye Zhu Meihua Xie Hua Yang |
| author_sort | Caiyun Lin |
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| description | Abstract Objective To assess the triage value of multigene methylation testing for cervical intraepithelial neoplasia 2 and above (CIN2+) in high-risk human papillomavirus (hrHPV) positive patients. Methods 634 hrHPV-positive cases were selected from the gynecology outpatient clinic at Hainan Women and Children’s Medical Center between July 2022 and April 2024. Out of these, 274 patients were excluded based on the inclusion and exclusion criteria. A total of 360 patients were evaluated for hrHPV, cytology, histopathology, and DNA methylation across multiple loci. These patients were categorized into five groups based on their histopathological diagnoses: control group, CIN1 group, CIN2 group, CIN3 group, and cervical cancer (CC) group. The triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients was evaluated by calculating the positivity of candidate gene methylation, sensitivity, specificity, area under the curve (AUC), and other performance indicators. Results Among the 17 candidate genes (ST6GALNAC5, PAX1, AJAP1, CDKN2A, ZNF671, GATA4, MAL, POU4F3, RXFP3, JAM3, MIR124, LHX8, SOX1, ASTN1, SOX17, DLX1, and ITGA4), ITGA4 methylation testing demonstrated the highest diagnostic efficacy for detecting CIN2 + lesions, with an AUC of 0.866 (95% confidence interval [CI]: 0.806–0.925). This method exhibited a sensitivity of 75.32% (95% CI: 0.647–0.836) and a specificity of 96.45% (95% CI: 0.936–0.981). The combined methylation test, which included all candidate genes, showed a higher specificity of 97.87% (95% CI: 0.954–0.990) compared to any individual gene methylation test. However, its sensitivity was lower, at 72.73% (95% CI: 0.619–0.814). Furthermore, the diagnostic accuracy of combining HPV16/18 testing with all candidate gene methylation tests for the diagnosis of CIN2 + was significantly greater than when HPV16/18 testing was combined with cytology. This combined approach had an AUC of 0.907 (95% CI: 0.858–0.955), a sensitivity of 72.73% (95% CI: 0.619–0.814), and a specificity of 98.58% (95% CI: 0.964–0.995). Conclusion Multigene methylation testing is an efficient triage test for CIN2 + in hrHPV-positive patients and has potential value in clinical practice. Combined HPV16/18 and multigene methylation testing for the triage of CIN2 + is significantly better than combined HPV16/18 and cytology testing. |
| format | Article |
| id | doaj-art-5f07f52c0e7f4e68b379d4fdf49f2e07 |
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| spelling | doaj-art-5f07f52c0e7f4e68b379d4fdf49f2e072025-08-20T02:17:09ZengBMCInfectious Agents and Cancer1750-93782025-04-0120111010.1186/s13027-025-00652-4Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patientsCaiyun Lin0Chenye Zhu1Meihua Xie2Hua Yang3Hainan Women and Children’s Medical CenterHainan Women and Children’s Medical CenterHainan Women and Children’s Medical CenterHainan Women and Children’s Medical CenterAbstract Objective To assess the triage value of multigene methylation testing for cervical intraepithelial neoplasia 2 and above (CIN2+) in high-risk human papillomavirus (hrHPV) positive patients. Methods 634 hrHPV-positive cases were selected from the gynecology outpatient clinic at Hainan Women and Children’s Medical Center between July 2022 and April 2024. Out of these, 274 patients were excluded based on the inclusion and exclusion criteria. A total of 360 patients were evaluated for hrHPV, cytology, histopathology, and DNA methylation across multiple loci. These patients were categorized into five groups based on their histopathological diagnoses: control group, CIN1 group, CIN2 group, CIN3 group, and cervical cancer (CC) group. The triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients was evaluated by calculating the positivity of candidate gene methylation, sensitivity, specificity, area under the curve (AUC), and other performance indicators. Results Among the 17 candidate genes (ST6GALNAC5, PAX1, AJAP1, CDKN2A, ZNF671, GATA4, MAL, POU4F3, RXFP3, JAM3, MIR124, LHX8, SOX1, ASTN1, SOX17, DLX1, and ITGA4), ITGA4 methylation testing demonstrated the highest diagnostic efficacy for detecting CIN2 + lesions, with an AUC of 0.866 (95% confidence interval [CI]: 0.806–0.925). This method exhibited a sensitivity of 75.32% (95% CI: 0.647–0.836) and a specificity of 96.45% (95% CI: 0.936–0.981). The combined methylation test, which included all candidate genes, showed a higher specificity of 97.87% (95% CI: 0.954–0.990) compared to any individual gene methylation test. However, its sensitivity was lower, at 72.73% (95% CI: 0.619–0.814). Furthermore, the diagnostic accuracy of combining HPV16/18 testing with all candidate gene methylation tests for the diagnosis of CIN2 + was significantly greater than when HPV16/18 testing was combined with cytology. This combined approach had an AUC of 0.907 (95% CI: 0.858–0.955), a sensitivity of 72.73% (95% CI: 0.619–0.814), and a specificity of 98.58% (95% CI: 0.964–0.995). Conclusion Multigene methylation testing is an efficient triage test for CIN2 + in hrHPV-positive patients and has potential value in clinical practice. Combined HPV16/18 and multigene methylation testing for the triage of CIN2 + is significantly better than combined HPV16/18 and cytology testing.https://doi.org/10.1186/s13027-025-00652-4Cervical cancerCervical intraepithelial neoplasiaMultigene methylation testingTriage value |
| spellingShingle | Caiyun Lin Chenye Zhu Meihua Xie Hua Yang Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients Infectious Agents and Cancer Cervical cancer Cervical intraepithelial neoplasia Multigene methylation testing Triage value |
| title | Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients |
| title_full | Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients |
| title_fullStr | Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients |
| title_full_unstemmed | Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients |
| title_short | Analysis of the triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients |
| title_sort | analysis of the triage value of multigene methylation testing for cin2 in hrhpv positive patients |
| topic | Cervical cancer Cervical intraepithelial neoplasia Multigene methylation testing Triage value |
| url | https://doi.org/10.1186/s13027-025-00652-4 |
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