Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study.

Autor: Bonde J; Molecular Pathology Laboratory, Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark., Floore A; Self-screen B.V, Amsterdam, The Netherlands., Ejegod D; Molecular Pathology Laboratory, Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark., Vink FJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands., Hesselink A; Self-screen B.V, Amsterdam, The Netherlands., van de Ven PM; Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Valenčak AO; Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia., Pedersen H; Molecular Pathology Laboratory, Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark., Doorn S; Self-screen B.V, Amsterdam, The Netherlands., Quint WG; DDL Diagnostic Laboratory, Rijswijk, The Netherlands., Petry KU; Department of Gynaecology and Obstetrics, Klinikum Wolfsburg, Germany., Poljak M; Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia., Stanczuk G; Department of Obstetrics and Gynaecology, Western Isles Hospital, Scotland, UK., Cuschieri K; HPV Research Group, Division of Pathology, University of Edinburgh, Scotland, UK., de Sanjosé S; Infections and Cancer Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain., Bleeker M; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands., Berkhof J; Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Meijer CJLM; Self-screen B.V, Amsterdam, The Netherlands.; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands., Heideman DAM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2021 Jan 15; Vol. 148 (2), pp. 396-405. Date of Electronic Publication: 2020 Oct 21.
DOI: 10.1002/ijc.33320
Abstrakt: In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID-SCREEN is a EU-multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124-2 methylation-based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124-2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV-positive cervical screening samples, from women 29-76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV-status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow-up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen-detected cervical cancers were found methylation-positive (sensitivity 95%). Overall specificity of FAM19A4/miR124-2 methylation test was 78.3% (n = 2013; 95%CI: 76-80). The negative predictive value of hrHPV positive, methylation-negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6-99.99), 96.9% for ≥CIN3 (95%CI: 96-98), and 93.0% for ≥CIN2 (95%CI: 92-94). Overall sensitivity for CIN3 using FAM19A4/miR124-2 methylation test was 77% (n = 228; 95%CI: 71-82). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the FAM19A4/miR124-2 methylation constitute an alternative/supplement to cytology as triage method to be investigated in real-life pilot implementation.
(© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)
Databáze: MEDLINE
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