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

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Abstract

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
Pages170-170
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
Number3
Volume26
ISSN (Print)1048-891X

Conference

Conference16th Biennial Meeting of the International Gynecologic Cancer Society
Abbreviated titleIGCS 2016
CountryPortugal
CityLisbon
Period29/10/1631/10/16

Fingerprint

Feasibility Studies
DNA Methylation
Genetic Markers
Uterine Cervical Neoplasms
Urine
Area Under Curve
Triage
Cell Biology
Genes
Urine Specimen Collection
Tumor Suppressor Genes
Early Detection of Cancer
Methylation
DNA

Keywords

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

Cite this

Rurup, W. F., van Trommel, N. E., van Splunter, A. P., Segerink, L. I., Kenter, G. G., Heideman, D. A. M., ... Steenbergen, R. D. M. (2016). Detection of DNA methylation markers in urine of cervical cancer patients: a feasibility study. In 16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS) (pp. 170-170). (Biennial Meeting of the International Gynecologic Cancer Society (IGCS); Vol. 26, No. 3). Philadelphia: LIPPINCOTT WILLIAMS & WILKINS.
Rurup, W.F. ; van Trommel, N.E. ; van Splunter, A.P. ; Segerink, L.I. ; Kenter, G.G. ; Heideman, D.A.M. ; van Gent, M. ; Pinedo, H.M. ; Snijders, P.J.F. ; van den Berg, A. ; Steenbergen, R.D.M. / Detection of DNA methylation markers in urine of cervical cancer patients : a feasibility study. 16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS). Philadelphia : LIPPINCOTT WILLIAMS & WILKINS, 2016. pp. 170-170 (Biennial Meeting of the International Gynecologic Cancer Society (IGCS); 3).
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title = "Detection of DNA methylation markers in urine of cervical cancer patients: a feasibility study",
abstract = "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.",
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author = "W.F. Rurup and {van Trommel}, N.E. and {van Splunter}, A.P. and L.I. Segerink and G.G. Kenter and D.A.M. Heideman and {van Gent}, M. and H.M. Pinedo and P.J.F. Snijders and {van den Berg}, A. and R.D.M. Steenbergen",
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Rurup, WF, van Trommel, NE, van Splunter, AP, Segerink, LI, Kenter, GG, Heideman, DAM, van Gent, M, Pinedo, HM, Snijders, PJF, van den Berg, A & Steenbergen, RDM 2016, Detection of DNA methylation markers in urine of cervical cancer patients: a feasibility study. in 16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS). Biennial Meeting of the International Gynecologic Cancer Society (IGCS), no. 3, vol. 26, LIPPINCOTT WILLIAMS & WILKINS, Philadelphia, pp. 170-170, 16th Biennial Meeting of the International Gynecologic Cancer Society, Lisbon, Portugal, 29/10/16.

Detection of DNA methylation markers in urine of cervical cancer patients : a feasibility study. / Rurup, W.F.; van Trommel, N.E.; van Splunter, A.P.; Segerink, L.I.; Kenter, G.G.; Heideman, D.A.M.; van Gent, M.; Pinedo, H.M.; Snijders, P.J.F.; van den Berg, A.; Steenbergen, R.D.M.

16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS). Philadelphia : LIPPINCOTT WILLIAMS & WILKINS, 2016. p. 170-170 (Biennial Meeting of the International Gynecologic Cancer Society (IGCS); Vol. 26, No. 3).

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

TY - GEN

T1 - Detection of DNA methylation markers in urine of cervical cancer patients

T2 - a feasibility study

AU - Rurup, W.F.

AU - van Trommel, N.E.

AU - van Splunter, A.P.

AU - Segerink, L.I.

AU - Kenter, G.G.

AU - Heideman, D.A.M.

AU - van Gent, M.

AU - Pinedo, H.M.

AU - Snijders, P.J.F.

AU - van den Berg, A.

AU - Steenbergen, R.D.M.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

KW - EWI-27559

KW - IR-103272

KW - METIS-321669

M3 - Conference contribution

T3 - Biennial Meeting of the International Gynecologic Cancer Society (IGCS)

SP - 170

EP - 170

BT - 16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS)

PB - LIPPINCOTT WILLIAMS & WILKINS

CY - Philadelphia

ER -

Rurup WF, van Trommel NE, van Splunter AP, Segerink LI, Kenter GG, Heideman DAM et al. Detection of DNA methylation markers in urine of cervical cancer patients: a feasibility study. In 16th Biennal Meetin of the International Gynecologic Cancer Society (IGCS). Philadelphia: LIPPINCOTT WILLIAMS & WILKINS. 2016. p. 170-170. (Biennial Meeting of the International Gynecologic Cancer Society (IGCS); 3).