Triage of human papillomavirus infected women by methylation analysis in first-void urine

Severien Van Keer; Annina P van Splunter; Jade Pattyn; Annemie De Smet; Sereina A Herzog; Xaveer Van Ostade; Wiebren A A Tjalma; Margareta Ieven; Pierre Van Damme; Renske D M Steenbergen; Alex Vorsters

doi:https://doi.org/10.1038/s41598-021-87329-1

Triage of human papillomavirus infected women by methylation analysis in first-void urine

Severien Van Keer, Annina P van Splunter, Jade Pattyn, Annemie De Smet, Sereina A Herzog, Xaveer Van Ostade, Wiebren A A Tjalma, Margareta Ieven, Pierre Van Damme, Renske D M Steenbergen, Alex Vorsters

CCA - Imaging and biomarkers (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

15 Citations (Scopus)

Abstract

Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

Original language	English
Article number	7862
Pages (from-to)	7862
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-87329-1
Publication status	Published - Dec 2021

Access to Document

https://doi.org/10.1038/s41598-021-87329-1

Cite this

@article{a0e82846eb01450ba93d178e2314d470,

title = "Triage of human papillomavirus infected women by methylation analysis in first-void urine",

abstract = "Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.",

author = "{Van Keer}, Severien and {van Splunter}, {Annina P} and Jade Pattyn and {De Smet}, Annemie and Herzog, {Sereina A} and {Van Ostade}, Xaveer and Tjalma, {Wiebren A A} and Margareta Ieven and {Van Damme}, Pierre and Steenbergen, {Renske D M} and Alex Vorsters",

note = "Funding Information: We would like to express our gratitude to all women who volunteered to participate in this study, and thank Dr. L. Ameryckx for her assistance in recruiting participants. We are grateful for the excellent laboratory and logistic assistance of Ms. S. Biesmans and furthermore thank Prof. N. Hens, PhD for statistical support. This work was supported by the Industrial Research Fund of the University of Antwerp, Belgium under grant number PS ID 32387. S. Van Keer is supported by a junior postdoctoral fellowship of the Research Foundation—Flanders (FWO), Belgium under grant number 1240220N. J. Pattyn is supported by the Royal Belgian Academy of Medicine. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = dec,

doi = "https://doi.org/10.1038/s41598-021-87329-1",

language = "English",

volume = "11",

pages = "7862",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - Triage of human papillomavirus infected women by methylation analysis in first-void urine

AU - Van Keer, Severien

AU - van Splunter, Annina P

AU - Pattyn, Jade

AU - De Smet, Annemie

AU - Herzog, Sereina A

AU - Van Ostade, Xaveer

AU - Tjalma, Wiebren A A

AU - Ieven, Margareta

AU - Van Damme, Pierre

AU - Steenbergen, Renske D M

AU - Vorsters, Alex

N1 - Funding Information: We would like to express our gratitude to all women who volunteered to participate in this study, and thank Dr. L. Ameryckx for her assistance in recruiting participants. We are grateful for the excellent laboratory and logistic assistance of Ms. S. Biesmans and furthermore thank Prof. N. Hens, PhD for statistical support. This work was supported by the Industrial Research Fund of the University of Antwerp, Belgium under grant number PS ID 32387. S. Van Keer is supported by a junior postdoctoral fellowship of the Research Foundation—Flanders (FWO), Belgium under grant number 1240220N. J. Pattyn is supported by the Royal Belgian Academy of Medicine. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

AB - Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

UR - http://www.scopus.com/inward/record.url?scp=85104243252&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s41598-021-87329-1

DO - https://doi.org/10.1038/s41598-021-87329-1

M3 - Article

C2 - 33846517

SN - 2045-2322

VL - 11

SP - 7862

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 7862

ER -

Triage of human papillomavirus infected women by methylation analysis in first-void urine

Abstract

Access to Document

Other files and links

Cite this