FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study |
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| Authors: | Frederique J Vink Chris JLM Meijer Gary M Clifford Mario Poljak Anja Oštrbenk Karl Ulrich Petry Beate Rothe Jesper Bonde Helle Pedersen Silvia de Sanjosé Montserrat Torres Marta del Pino Wim GV Quint Kate Cuschieri Elia Alcañiz Boada Nienke E van Trommel Birgit I Lissenberg-Witte Arno N Floore Albertus T Hesselink Renske DM Steenbergen Maaike CG Bleeker Daniëlle AM Heideman |
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| Institution: | 1. Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands;2. International Agency for Research on Cancer, Lyon, France;3. Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia;4. Department of Gynecologic Oncology, Klinikum Wolfsburg, Wolfsburg, Germany;5. Institute for Clinical Chemistry, Laboratory and Transfusion Medicine, Wolfsburg, Germany;6. Molecular Pathology Laboratory, Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark;7. PATH, Seattle, WA;8. Infections and Cancer Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain;9. Faculty of Medicine, Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain;10. DDL Diagnostic Laboratory, Rijswijk, The Netherlands;11. Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom;12. HPV Research Group, Division of Pathology, University of Edinburgh, Edinburgh, United Kingdom;13. Department of Gynaecologic Oncology, Centre of Gynaecologic Oncology Amsterdam, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, The Netherlands;14. Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Biostatistics, Amsterdam, The Netherlands;15. Self-screen B.V, Amsterdam, The Netherlands |
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| Abstract: | Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In our study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation-specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. |
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| Keywords: | DNA hypermethylation human genome methylation human papillomavirus biomarker cervical carcinoma cervical screening |
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