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

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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 languageEnglish
Article number7862
Pages (from-to)7862
JournalScientific reports
Issue number1
Publication statusPublished - Dec 2021

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