ArticleInternational journal of cancer2021
Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study.
Article in International journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- DNA methylation as a triage marker for colposcopy referral in HPV-based cervical cancer screening: a systematic review and meta-analysis.Clinical epigenetics · 2023Pooled it
- Value of a catch-up HPV test in women aged 65 and above: A Danish population-based nonrandomized intervention study.PLoS medicine · 2023Trial
- Triage Performance of FAM19A4/miR124-2 Methylation: 18-Month Follow-Up Results From a Prospective Observational Study Within the Dutch Primary HPV-Based Cervical Screening Program.International journal of cancer · 2026Observational
- Clinical Utility of Cytological Methylation Assay in Cervical Cancer Screening Across Various Cervical Transformation Zones.International journal of cancer · 2026Article
- Analysis of DNA methylation markers for diagnosing cervical precancer and cancer: A single-center cross-sectional study.Oncology letters · 2026Article
- HPV-Associated Field Cancerization: Molecular Alterations in Histologically Normal Tissues and Implications for Early Detection and Cancer Prevention.Current issues in molecular biology · 2026Review
- Review
- Methylation biomarkers in non-regressive cervical intraepithelial neoplasia grade 2 lesions: an epigenome wide association study.British journal of cancer · 2026Article
- Primary Human Papillomavirus Screening Versus Cytology for Detection of Cervical Intraepithelial Neoplasia Grade 2 or Higher in Poland: a Parallel-Group, Randomized Controlled Trial.The Lancet regional health. Europe · 2026Article
- Biology-aligned cervical cancer screening: target-centric biomarkers and next-generation diagnostic platforms.Biomarker research · 2026Review
- Article
- Genotype-Specific HPV mRNA Triage Improves Colposcopy Efficiency Compared with Cytology and ATHENA-Derived Triage: A Population-Based Study of HPV DNA-Positive Women.Pathogens (Basel, Switzerland) · 2026Article
- Effectiveness analysis and clinical application potential exploration of combined detection of PAX1/JAM3 gene methylation in early diagnosis of cervical precancerous lesions.Clinical epigenetics · 2026Article
- Human Papillomavirus in Reproductive Health and Pregnancy: Clinical Implications, Outcomes, and a Comprehensive Review of Vaccination.Vaccines · 2026Review
- Epidemiology and prevention of HPV-driven cervical cancer in urban-rural China: a population-based study of 60,280 women.Scientific reports · 2026Article
- HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches.International journal of molecular sciences · 2026Review
- DNA Methylation in Cervical Intraepithelial Neoplasia and Cervical Cancer: Triage and Management.Current topics in microbiology and immunology · 2026Review
- Recent advancement in inflammatory biomarkers for cervical cancer diagnosis and therapy.Frontiers in oncology · 2026Review
- Optimization of RNAscope for HPV mRNA detection in liquid-based cervical cytology samples.Frontiers in oncology · 2026Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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