Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women
More evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions...
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MDPI AG
2023-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/1/46 |
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| author | Remila Rezhake Yan Wang Xuelian Zhao Marc Arbyn Guqun Shen Qinjing Pan Xun Zhang Yuanming Zhang Fanghui Zhao Youlin Qiao |
| author_facet | Remila Rezhake Yan Wang Xuelian Zhao Marc Arbyn Guqun Shen Qinjing Pan Xun Zhang Yuanming Zhang Fanghui Zhao Youlin Qiao |
| author_sort | Remila Rezhake |
| collection | DOAJ |
| description | More evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions among hrHPV-positive women was evaluated based on a population-based cohort study from China. Overall methylation positivity was 12.4% among hrHPV-positive women. Methylation-positive women had significantly higher risks of hrHPV persistence at 12M and 24M follow-up (RR<sub>12M</sub> = 1.9, 95%CI: 1.5–2.6 and RR<sub>24M</sub> = 1.7, 95%CI: 1.2–2.5). For CIN2+, cross-sectional triage sensitivity of methylation was similar to HPV16/18 (70.6% vs. 64.7%, p<sub>exact</sub> = 1.000), but was lower than cytology (94.1%), although not significantly (p<sub>exact</sub> = 0.213). The specificity (91.2%) of methylation was significantly higher than other triage methods (<i>p</i> < 0.001 for all). The longitudinal sensitivity of methylation over 24M follow-up was 56.0%, lower (but not significantly so) than HPV16/18 (64.0%, p<sub>exact</sub> = 0.688) and cytology (76.0%, p<sub>exact</sub> = 0.125). Methylation testing showed high positive predictive values for CIN2+ (41.4% at baseline, 50.0% at 24-month), while the CIN2+ risk of methylation negative women (cNPV) remained considerable (2.5% at baseline, 6.9% at 24-month). Study findings indicate that methylation has better specificity and predictive values for the presence or development of cervical precancer and might therefore be considered for the strategy of HPV screening and methylation triage followed by immediate treatment of triage-positive women and delayed follow-up of hrHPV-positive/methylation-negative women. |
| first_indexed | 2024-03-08T09:44:33Z |
| format | Article |
| id | doaj.art-533f93693d694f079fee4433f5697a53 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-08T09:44:33Z |
| publishDate | 2023-12-01 |
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| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-533f93693d694f079fee4433f5697a532024-01-29T14:25:32ZengMDPI AGVaccines2076-393X2023-12-011214610.3390/vaccines12010046Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive WomenRemila Rezhake0Yan Wang1Xuelian Zhao2Marc Arbyn3Guqun Shen4Qinjing Pan5Xun Zhang6Yuanming Zhang7Fanghui Zhao8Youlin Qiao9Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830000, ChinaCancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830000, ChinaDepartment of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaUnit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels B-1000, BelgiumCancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830000, ChinaDepartment of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaCancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830000, ChinaDepartment of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaCancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830000, ChinaMore evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions among hrHPV-positive women was evaluated based on a population-based cohort study from China. Overall methylation positivity was 12.4% among hrHPV-positive women. Methylation-positive women had significantly higher risks of hrHPV persistence at 12M and 24M follow-up (RR<sub>12M</sub> = 1.9, 95%CI: 1.5–2.6 and RR<sub>24M</sub> = 1.7, 95%CI: 1.2–2.5). For CIN2+, cross-sectional triage sensitivity of methylation was similar to HPV16/18 (70.6% vs. 64.7%, p<sub>exact</sub> = 1.000), but was lower than cytology (94.1%), although not significantly (p<sub>exact</sub> = 0.213). The specificity (91.2%) of methylation was significantly higher than other triage methods (<i>p</i> < 0.001 for all). The longitudinal sensitivity of methylation over 24M follow-up was 56.0%, lower (but not significantly so) than HPV16/18 (64.0%, p<sub>exact</sub> = 0.688) and cytology (76.0%, p<sub>exact</sub> = 0.125). Methylation testing showed high positive predictive values for CIN2+ (41.4% at baseline, 50.0% at 24-month), while the CIN2+ risk of methylation negative women (cNPV) remained considerable (2.5% at baseline, 6.9% at 24-month). Study findings indicate that methylation has better specificity and predictive values for the presence or development of cervical precancer and might therefore be considered for the strategy of HPV screening and methylation triage followed by immediate treatment of triage-positive women and delayed follow-up of hrHPV-positive/methylation-negative women.https://www.mdpi.com/2076-393X/12/1/46methylationcervical cancerHPVcancer screeningearly detectiontriage |
| spellingShingle | Remila Rezhake Yan Wang Xuelian Zhao Marc Arbyn Guqun Shen Qinjing Pan Xun Zhang Yuanming Zhang Fanghui Zhao Youlin Qiao Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women Vaccines methylation cervical cancer HPV cancer screening early detection triage |
| title | Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women |
| title_full | Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women |
| title_fullStr | Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women |
| title_full_unstemmed | Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women |
| title_short | Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women |
| title_sort | performance of human gene epb41l3 and hpv 16 18 viral dna methylation to triage hrhpv positive women |
| topic | methylation cervical cancer HPV cancer screening early detection triage |
| url | https://www.mdpi.com/2076-393X/12/1/46 |
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