1. Methylation analysis in urine fractions for optimal CIN3 and cervical cancer detection.
- Author
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van den Helder R, van Trommel NE, van Splunter AP, Lissenberg-Witte BI, Bleeker MCG, and Steenbergen RDM
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Cervix Uteri pathology, Cervix Uteri virology, Early Detection of Cancer methods, Female, Humans, Mass Screening methods, Middle Aged, Statistics, Nonparametric, Uterine Cervical Neoplasms urine, Uterine Cervical Dysplasia urine, DNA Methylation, Papillomavirus Infections diagnosis, Papillomavirus Infections urine, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Dysplasia diagnosis
- Abstract
Introduction: Urine sampling is an interesting solution for CIN3 and cervical cancer detection. Urine can be separated in different fractions: full void urine, urine sediment and urine supernatant. We aimed to determine which urine fraction is most competent for CIN3 and cervical cancer detection by methylation analysis., Methods: Urine samples (27 controls, 30 CIN3 and 17 cervical cancer) were processed into 3 fractions and tested for 5 methylation markers (ASCL1, GHSR, LHX8, SST, ZIC1). We determined Spearman correlation coefficients between fractions, compared methylation levels and calculated AUCs for CIN3 and cancer detection., Results: In general strong correlations (r > 0.60) were found between urine fractions. Methylation levels increased significantly with severity of underlying disease in all urine fractions. CIN3 and controls differed significantly for 2 markers in full void urine, 4 markers in urine sediment and 1 marker in urine supernatant, with AUCs of 0.55-0.79. Comparison of cancer to controls was highly significant for all markers in all fractions, yielding AUCs of 0.87-0.99., Conclusion: Methylation analysis performs excellent in all urine fractions for cervical cancer detection. Our results indicate the potential of CIN3 detection by urinary methylation analysis, and demonstrate that urine sediment performs best to detect CIN3., Competing Interests: Declaration of competing interests Rianne van den Helder, Nienke E. van Trommel, Annina P. van Splunter, Birgit I. Lissenberg-Witte and Maaike C.G. Bleeker have no interests to declare. Renske D.M. Steenbergen has a minority share in Self-screen B·V., a spin-off company of Amsterdam UMC, location VUmc. Self-screen B.V. holds patents related to the work (i.e., high-risk HPV test and methylation markers for cervical screening) and has developed and manufactured the methylation assay, which is licensed to Qiagen (QIAsure® Methylation Test)., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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