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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.
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1 University of Antwerp, Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, Wilrijk, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681)
2 Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
3 University of Antwerp, Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, Wilrijk, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681)
4 University of Antwerp, Laboratory of Proteinscience, Proteomics & Epigenetic Signalling (PPES), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Wilrijk, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681)
5 Antwerp University Hospital (UZA), Multidisciplinary Breast Clinic, Unit Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Edegem, Belgium (GRID:grid.411414.5) (ISNI:0000 0004 0626 3418); University of Antwerp, Molecular Imaging, Pathology, Radiotherapy, Oncology (MIPRO), Faculty of Medicine and Health Sciences, Wilrijk, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681)
6 University of Antwerp, Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, Wilrijk, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681)