Detection of DNA methylation markers in urine of cervical cancer patients: a feasibility study

W.F. Rurup, N.E. van Trommel, A.P. van Splunter, L.I. Segerink, G.G. Kenter, D.A.M. Heideman, M. van Gent, H.M. Pinedo, P.J.F. Snijders, A. van den Berg, R.D.M. Steenbergen

    Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

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    Background and aims: Current cervical screening programs use cervical cytology and is likely to be replaced by primary hrHPV testing in many Western countries. Cytology has a low sensitivity (50-80%), which is largely improved by hrHPV testing. Due to its lower positive predictive value hrHPV testing requires further triage testing. Analysis of DNA methylation of host cell tumor suppressor genes provides promising triage strategy for hrHPV-positive women. Urine collection is expected to increase the uptake of cervical screening programs, and hrHPV testing in urine appears promising. We performed a feasibility study to detect cervical cancer with DNA methylation testing in urine.

    Methods: Cervical scrapes and urine samples were collected from 29 cervical cancer patient and urine from 24 healthy controls. Extracted DNAs were tested for hrHPV presence and DNA methylation of 6 genes which were previously found to enable cervical (pre)cancer detection in cervical scrapes.

    Results: A 97% (28/29) concordance was found between hrHPV testing on cervical scrapes and urine samples. DNA methylation levels of all 6 genes were significantly increased in urine samples of cervical cancer patients compared to controls. Receiver operating curve analysis showed a maximum AUC 0.92 (95%CI 0.80-1.0) with 4 out of 6 genes having an AUC>0.86. Moreover, DNA methylation levels in urine were highly correlated to those detected in cervical scrapes of the same patients (Spearmann correlation = 0.83)

    Conclusions: DNA methylation testing in urine has a high diagnostic accuracy (up to AUC 0.92) to detect cervical cancer, warranting further exploration of methylation markers for use in urine-based cervical cancer screening programs.

    Original languageEnglish
    Title of host publication16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS)
    Place of PublicationPhiladelphia
    PublisherLippincott Williams & Wilkins
    Number of pages1
    Publication statusPublished - Oct 2016
    Event16th Biennial Meeting of the International Gynecologic Cancer Society: Uniting the Globe in the Fight Against Gynecologic Cancer - Lisbon, Portugal
    Duration: 29 Oct 201631 Oct 2016
    Conference number: 16th

    Publication series

    NameBiennial Meeting of the International Gynecologic Cancer Society (IGCS)
    PublisherLippincott Williams & Wilkins
    ISSN (Print)1048-891X


    Conference16th Biennial Meeting of the International Gynecologic Cancer Society
    Abbreviated titleIGCS 2016


    • EWI-27559
    • IR-103272
    • METIS-321669


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