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DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WIDTM-qCIN test
C. Herzog, K. Sundström, A. Jones, I. Evans, JE. Barrett, J. Wang, E. Redl, L. Schreiberhuber, L. Costas, S. Paytubi, L. Dostalek, M. Zikan, D. Cibula, G. Sroczynski, U. Siebert, J. Dillner, M. Widschwendter
Language English Country Germany
Document type Journal Article
Grant support
742432
European Research Council - International
NLK
BioMedCentral
from 2010-09-01
BioMedCentral Open Access
from 2011
Directory of Open Access Journals
from 2011
Free Medical Journals
from 2011
PubMed Central
from 2010
Europe PubMed Central
from 2010
ProQuest Central
from 2015-01-01
Open Access Digital Library
from 2010-01-01
Open Access Digital Library
from 2011-01-01
Health & Medicine (ProQuest)
from 2015-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2010
Springer Nature OA/Free Journals
from 2010-09-01
- MeSH
- Alphapapillomavirus * MeSH
- Early Detection of Cancer MeSH
- Adult MeSH
- Uterine Cervical Dysplasia * diagnosis genetics MeSH
- Papillomavirus Infections * diagnosis genetics MeSH
- Humans MeSH
- DNA Methylation MeSH
- Uterine Cervical Neoplasms * diagnosis genetics MeSH
- Papillomaviridae genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients. RESULTS: The WIDTM-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WIDTM-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WIDTM-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation. CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WIDTM-qCIN, a PCR-based DNAme test. The WIDTM-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.
Center for Health Decision Science Boston MA USA
Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA
Department of Health Policy and Management Harvard T H Chan School of Public Health Boston MA USA
Department of Laboratory Medicine Division of Pathology Karolinska Institutet Stockholm Sweden
Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden
Medical Diagnostics Karolinska Karolinska University Hospital Stockholm Sweden
Research Institute for Biomedical Aging Research Universität Innsbruck 6020 Innsbruck Austria
References provided by Crossref.org
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