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DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohortLeeuwen, Robert W., van ...Objective triage strategies are required to prevent unnecessary referrals for colposcopy in population-based screening programs using primary high-risk human papillomavirus (hrHPV) testing. We have ... identified several DNA methylation markers with high sensitivity and specificity for detection of high-grade cervical intraepithelial neoplasia or worse (CIN2+) in women referred for colposcopy. Our study assessed diagnostic potential of these methylation markers in a hrHPV-positive screening cohort. All six markers (JAM3, EPB41L3, C13orf18, ANKRD18CP, ZSCAN1 and SOX1) showed similar association across histology in the hrHPV-positive cohort when compared to the Dutch cohort (each p > 0.15). Sensitivity for CIN2+ was higher using methylation panel C13orf18/EPB41L3/JAM3 compared to the other 2 panels (80% vs. 60% (ANKRD18CP/C13orf18/JAM3) and 63% (SOX1/ZSCAN1), p = 0.01). For CIN3+ all three methylation panels showed comparable sensitivity ranging from 68% (13/19) to 95% (18/19). Specificity of SOX1/ZSCAN1 panel (84%, 167/200) was considerably higher compared to ANKRD18CP/C13orf18/JAM3 (68%, 136/200, p = 2 X 10-5) and C13orf18/EPB41L3/JAM3 (66%, 132/200, p = 2 X 10-7). High negative predictive value (NPV) (91-95% and 96-99%) was observed for CIN2+ and CIN3+, for all three methylation panels, while positive predictive value (PPV) varied from 25 to 40% for CIN2+ and 15-27% for CIN3+. Interestingly, 118/235 samples were negative for all six markers (including 106 controls (89.8%), 6 CIN1 (5.1%), 5 CIN2 (4.2%) and 1 CIN3 (0.8%)). Methylation results from both independent cohorts were comparable as well as high sensitivity for detection of cervical cancer and its high-grade precursors in hrHPV-positive population. Our study therefore validates these methylation marker panels as triage test either in hrHPV-based or abnormal cytology-based screening programs.Source: International journal of cancer = Journal international du cancer. - ISSN 0020-7136 (Vol. 144, no. 4, Feb. 2019, str. 746-754)Type of material - article, component partPublish date - 2019Language - englishCOBISS.SI-ID - 34126041
Author
Leeuwen, Robert W., van |
Oštrbenk Valenčak, Anja |
Poljak, Mario, 1965- |
Zee, Ate G. J., van der |
Schuuring, Ed |
Wisman, Bea A.
Topics
(pred) maligni rak materničnega vratu |
markerji DNA metilacije |
odkrivanje raka materničnega vratu |
(pre)malignant cervical cancer |
DNA methylation markers |
cervical cancer screening
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source: International journal of cancer = Journal international du cancer. - ISSN 0020-7136 (Vol. 144, no. 4, Feb. 2019, str. 746-754)
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Leeuwen, Robert W., van | ![]() |
Oštrbenk Valenčak, Anja | 35359 |
Poljak, Mario, 1965- | 11622 |
Zee, Ate G. J., van der | ![]() |
Schuuring, Ed | ![]() |
Wisman, Bea A. | ![]() |
Source: Personal bibliographies
and: SICRIS
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