Comparing the performance ofFAM19A4methylation analysis, cytology and HPV16/18 genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive women of a gynecologic outpatient population (COMETH study)
| Autor: | Wim Quint, Daniëlle A.M. Heideman, Peppino G.C.M. Graziosi, Folkert J. van Kemenade, Peter J.F. Snijders, Renske D.M. Steenbergen, René H.M. Verheijen, Roosmarijn Luttmer, Johannes Berkhof, W. Marchien van Baal, Maaike G. Dijkstra, Lise M.A. De Strooper, W Abraham ter Harmsel, Chris J.L.M. Meijer, Theo J.M. Helmerhorst, Lawrence Rozendaal, Margot H. Uijterwaal |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cervical cancer Gynecology Cancer Research medicine.medical_specialty education.field_of_study business.industry Population medicine.disease Cervical intraepithelial neoplasia female genital diseases and pregnancy complications 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Cytology DNA methylation medicine Outpatient clinic Population study business education Genotyping |
| Zdroj: | International Journal of Cancer. 138:992-1002 |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.29824 |
| Popis: | Recently, DNA methylation analysis of FAM19A4 in cervical scrapes has been shown to adequately detect high-grade cervical intraepithelial neoplasia and cervical cancer (≥ CIN3) in high-risk HPV (hrHPV)-positive women. Here, we compared the clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18 genotyping, separately and in combination, for ≥ CIN3 detection in hrHPV-positive women participating in a prospective observational multi-center cohort study. The study population comprised hrHPV-positive women aged 18-66 years, visiting a gynecological outpatient clinic. From these women, cervical scrapes and colposcopy-directed biopsies (for histological confirmation) were obtained. Cervical scrapes were analyzed for FAM19A4 gene promoter methylation, cytology and HPV16/18 genotyping. Methylation analysis was performed by quantitative methylation-specific PCR (qMSP). Sensitivities and specificities for ≥ CIN3 were compared between tests. Stratified analyses were performed for variables that potentially influence marker performance. Of all 508 hrHPV-positive women, the sensitivities for ≥ CIN3 of cytology, FAM19A4 methylation analysis, and cytology combined with HPV16/18 genotyping were 85.6, 75.6 and 92.2%, respectively, with corresponding specificities of 49.8, 71.1 and 29.4%, respectively. Both sensitivity and specificity of FAM19A4 methylation analysis were associated with age (p ≤ 0.001 each). In women ≥ 30 years (n = 287), ≥ CIN3 sensitivity of FAM19A4 methylation analysis was 88.3% (95%CI: 80.2-96.5) which was noninferior to that of cytology [85.5% (95%CI: 76.0-94.0)], at a significantly higher specificity [62.1% (95%CI: 55.8-68.4) compared to 47.6% (95%CI: 41.1-54.1)]. In conclusion, among hrHPV-positive women from an outpatient population aged ≥ 30 years, methylation analysis of FAM19A4 is an attractive marker for the identification of women with ≥ CIN3. |
| Databáze: | OpenAIRE |
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