| Autor: |
Dick S; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Verhoef L; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., De Strooper LM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Ciocănea-Teodorescu I; Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology & Biostatistics, De Boelelaan 1117, Amsterdam, The Netherlands., Wisman GBA; University of Groningen, University Medical Centre Groningen, Gynaecologic Oncology, Cancer Research Center Groningen, Groningen, The Netherlands., Meijer CJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Bleeker MC; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Steenbergen RD; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Heideman DA; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands. |
| Abstrakt: |
Aim: To evaluate the triage performance of six host-cell DNA methylation markers derived from two genome-wide discovery screens for detection of cervical precancer (cervical intraepithelial neoplasia 3 [CIN]) and cancer. Materials & methods: Human papillomavirus-positive cervical scrapes of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analyzed for methylation of ASCL1 , LHX8 , ST6GALNAC5 , GHSR , SST and ZIC1 . Results: Methylation levels increased significantly with disease severity (all markers p < 0.001). Three markers ( ASCL1 , LHX8 , ZIC1 ) showed receiver operating characteristic curves with area under the curve >0.800 after leave-one-out cross-validation. Bi-marker panel ASCL1/LHX8 had highest area under the curve (0.882), and detected 83.4% of CIN3 and all cervical cancers at specificity of 82.4%. Conclusion: All six methylation markers showed an equivalent, high performance for the triage of human papillomavirus-positive women using cervical scrapes with complementarity between markers. |
