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Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial
Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492122/ https://www.ncbi.nlm.nih.gov/pubmed/30412281 http://dx.doi.org/10.1002/ijc.31976 |
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author | Cook, Darrel A. Krajden, Mel Brentnall, Adam R. Gondara, Lovedeep Chan, Tracy Law, Jennifer H. Smith, Laurie W. van Niekerk, Dirk J. Ogilvie, Gina S. Coldman, Andrew J. Warman, Rhian Reuter, Caroline Cuzick, Jack Lorincz, Attila T. |
author_facet | Cook, Darrel A. Krajden, Mel Brentnall, Adam R. Gondara, Lovedeep Chan, Tracy Law, Jennifer H. Smith, Laurie W. van Niekerk, Dirk J. Ogilvie, Gina S. Coldman, Andrew J. Warman, Rhian Reuter, Caroline Cuzick, Jack Lorincz, Attila T. |
author_sort | Cook, Darrel A. |
collection | PubMed |
description | Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens. |
format | Online Article Text |
id | pubmed-6492122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64921222019-05-06 Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial Cook, Darrel A. Krajden, Mel Brentnall, Adam R. Gondara, Lovedeep Chan, Tracy Law, Jennifer H. Smith, Laurie W. van Niekerk, Dirk J. Ogilvie, Gina S. Coldman, Andrew J. Warman, Rhian Reuter, Caroline Cuzick, Jack Lorincz, Attila T. Int J Cancer Tumor Markers and Signatures Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens. John Wiley & Sons, Inc. 2018-12-24 2019-05-15 /pmc/articles/PMC6492122/ /pubmed/30412281 http://dx.doi.org/10.1002/ijc.31976 Text en © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Tumor Markers and Signatures Cook, Darrel A. Krajden, Mel Brentnall, Adam R. Gondara, Lovedeep Chan, Tracy Law, Jennifer H. Smith, Laurie W. van Niekerk, Dirk J. Ogilvie, Gina S. Coldman, Andrew J. Warman, Rhian Reuter, Caroline Cuzick, Jack Lorincz, Attila T. Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title | Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title_full | Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title_fullStr | Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title_full_unstemmed | Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title_short | Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial |
title_sort | evaluation of a validated methylation triage signature for human papillomavirus positive women in the hpv focal cervical cancer screening trial |
topic | Tumor Markers and Signatures |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492122/ https://www.ncbi.nlm.nih.gov/pubmed/30412281 http://dx.doi.org/10.1002/ijc.31976 |
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