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. 2023 Jul 15;153(2):341-351.
doi: 10.1002/ijc.34504. Epub 2023 Mar 23.

DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes

Birgit M M Wever  1   2 , Rianne van den Helder  1   2   3 , Annina P van Splunter  1   2 , Mignon D J M van Gent  2   4 , Jenneke C Kasius  2   4 , Johannes W Trum  3 , Harold R Verhoeve  5 , Wilhelmina M van Baal  6 , Alicia Hulbert  7 , Lisanne Verhoef  1   2 , Daniëlle A M Heideman  1   2 , Birgit I Lissenberg-Witte  2   8 , Nienke E van Trommel  3 , Renske D M Steenbergen  1   2 , Maaike C G Bleeker  1   2
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DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes

Birgit M M Wever et al. Int J Cancer. .

Abstract

Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P < .01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.

Keywords: DNA methylation; cervical scrape; endometrial cancer; urine; vaginal sample.

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References

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