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Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease

Cervical screening by high-risk HPV (hrHPV) testing requires additional risk stratification (triage), as most infections are transient and only a subset of hrHPV-positive women harbours clinically relevant disease. Molecular triage markers such as microRNAs (miRNAs) and DNA methylation markers are p...

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Autores principales: Babion, Iris, De Strooper, Lise M.A., Luttmer, Roosmarijn, Bleeker, Maaike C.G., Meijer, Chris J.L.M., Heideman, Daniëlle A.M., Wilting, Saskia M., Steenbergen, Renske D.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557605/
https://www.ncbi.nlm.nih.gov/pubmed/30955437
http://dx.doi.org/10.1080/15592294.2019.1600390
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author Babion, Iris
De Strooper, Lise M.A.
Luttmer, Roosmarijn
Bleeker, Maaike C.G.
Meijer, Chris J.L.M.
Heideman, Daniëlle A.M.
Wilting, Saskia M.
Steenbergen, Renske D.M.
author_facet Babion, Iris
De Strooper, Lise M.A.
Luttmer, Roosmarijn
Bleeker, Maaike C.G.
Meijer, Chris J.L.M.
Heideman, Daniëlle A.M.
Wilting, Saskia M.
Steenbergen, Renske D.M.
author_sort Babion, Iris
collection PubMed
description Cervical screening by high-risk HPV (hrHPV) testing requires additional risk stratification (triage), as most infections are transient and only a subset of hrHPV-positive women harbours clinically relevant disease. Molecular triage markers such as microRNAs (miRNAs) and DNA methylation markers are particularly promising, as they can be objectively tested directly on hrHPV-positive scrapes and cervicovaginal self-samples. Here, we evaluated the marker potential of 10 candidate miRNAs in 209 hrHPV-positive scrapes of women with underlying precancer (cervical intraepithelial neoplasia, grade 2–3 (CIN2-3)), cancer, or without disease (CIN0/1). A predictive miRNA classifier for CIN3 detection was built using logistic regression, which was compared to and combined with DNA methylation marker FAM19A4. Markers were correlated to histology parameters and hrHPV genotype. A miRNA classifier consisting of miR-149, miR-20a, and miR-93 achieved an area under the curve (AUC) of 0.834 for CIN3 detection, which was not significantly different to that of FAM19A4 methylation (AUC: 0.862, p = 0.591). Combining miRNA and methylation analysis demonstrated complementarity between both marker types (AUC: 0.939). While the miRNA classifier seemed more predictive for CIN2, FAM19A4 methylation was particularly high in HPV16-positive and histologically advanced CIN3, i.e. CIN3 with high lesion volume. The miRNA classifier, FAM19A4 methylation, and the miRNA/methylation combination were highest in cancer-associated scrapes. In conclusion, a panel of three miRNAs is discriminatory for CIN3 in hrHPV-positive scrapes and can complement DNA methylation analysis for the efficient detection of cervical disease. Combined analysis of the two marker types warrants further evaluation as triage strategy in hrHPV-based screening.
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spelling pubmed-65576052019-06-19 Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease Babion, Iris De Strooper, Lise M.A. Luttmer, Roosmarijn Bleeker, Maaike C.G. Meijer, Chris J.L.M. Heideman, Daniëlle A.M. Wilting, Saskia M. Steenbergen, Renske D.M. Epigenetics Research Paper Cervical screening by high-risk HPV (hrHPV) testing requires additional risk stratification (triage), as most infections are transient and only a subset of hrHPV-positive women harbours clinically relevant disease. Molecular triage markers such as microRNAs (miRNAs) and DNA methylation markers are particularly promising, as they can be objectively tested directly on hrHPV-positive scrapes and cervicovaginal self-samples. Here, we evaluated the marker potential of 10 candidate miRNAs in 209 hrHPV-positive scrapes of women with underlying precancer (cervical intraepithelial neoplasia, grade 2–3 (CIN2-3)), cancer, or without disease (CIN0/1). A predictive miRNA classifier for CIN3 detection was built using logistic regression, which was compared to and combined with DNA methylation marker FAM19A4. Markers were correlated to histology parameters and hrHPV genotype. A miRNA classifier consisting of miR-149, miR-20a, and miR-93 achieved an area under the curve (AUC) of 0.834 for CIN3 detection, which was not significantly different to that of FAM19A4 methylation (AUC: 0.862, p = 0.591). Combining miRNA and methylation analysis demonstrated complementarity between both marker types (AUC: 0.939). While the miRNA classifier seemed more predictive for CIN2, FAM19A4 methylation was particularly high in HPV16-positive and histologically advanced CIN3, i.e. CIN3 with high lesion volume. The miRNA classifier, FAM19A4 methylation, and the miRNA/methylation combination were highest in cancer-associated scrapes. In conclusion, a panel of three miRNAs is discriminatory for CIN3 in hrHPV-positive scrapes and can complement DNA methylation analysis for the efficient detection of cervical disease. Combined analysis of the two marker types warrants further evaluation as triage strategy in hrHPV-based screening. Taylor & Francis 2019-04-08 /pmc/articles/PMC6557605/ /pubmed/30955437 http://dx.doi.org/10.1080/15592294.2019.1600390 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Babion, Iris
De Strooper, Lise M.A.
Luttmer, Roosmarijn
Bleeker, Maaike C.G.
Meijer, Chris J.L.M.
Heideman, Daniëlle A.M.
Wilting, Saskia M.
Steenbergen, Renske D.M.
Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title_full Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title_fullStr Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title_full_unstemmed Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title_short Complementarity between miRNA expression analysis and DNA methylation analysis in hrHPV-positive cervical scrapes for the detection of cervical disease
title_sort complementarity between mirna expression analysis and dna methylation analysis in hrhpv-positive cervical scrapes for the detection of cervical disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557605/
https://www.ncbi.nlm.nih.gov/pubmed/30955437
http://dx.doi.org/10.1080/15592294.2019.1600390
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