High-risk human papillomavirus testing in first-void urine as a novel and non-invasive cervical cancer screening modality-a Danish diagnostic test accuracy study
- PMID: 40457337
- PMCID: PMC12131459
- DOI: 10.1186/s12916-025-04149-0
High-risk human papillomavirus testing in first-void urine as a novel and non-invasive cervical cancer screening modality-a Danish diagnostic test accuracy study
Abstract
Background: First-void urine (FVU) collection for high-risk human papillomavirus (hrHPV) testing has game-changing potential to improve cervical cancer prevention among under-screened women who remain unreached by clinician-based cervical cancer screening and vaginal self-sampling. Yet, the wide variation in the clinical accuracy of hrHPV testing in urine for detecting high-grade cervical intraepithelial neoplasia (CIN2 + /CIN3 +) across studies and clinical settings highlights the importance of local piloting and validation. This study determined the relative clinical accuracy of hrHPV testing in FVU versus clinician-collected cervical samples to detect CIN2 + /CIN3 + in a Danish referral population.
Methods: In a diagnostic test accuracy study, paired FVU (10 mL Colli-Pee device; index test) and cervical samples (Cervex Combi brush; comparator test) were obtained from 325 women aged 23-64 years (median age 36.0 years (IQR 29-46) who were either referred for colposcopy and biopsy taking or a cervical excision (reference test; available for all participants). Samples were tested using Allplex HR HPV DNA extended genotyping assay. Same absolute cut-off for hrHPV positivity applied for cervical samples was used for FVU. Of the 325 women, 145 (44.6%), 180 (55.4%), and 138 (42.5%) were diagnosed with < CIN2, CIN2 + , and CIN3 + , respectively.
Results: Sensitivity to detect CIN2 + (ratio 0.97, 95% CI 0.92-1.02, pMCN = 0.33) and CIN3 + (ratio 0.95, 95% CI 0.90-1.00, pMCN = 0.09) using hrHPV testing in FVU samples was not significantly different to hrHPV testing in cervical samples, whereas specificity for < CIN2 (ratio 0.67, 95% CI 0.46-0.96, pMCN = 0.04) was significantly lower in FVU than on cervical samples. Moderate to excellent hrHPV test agreements between paired samples were demonstrated (Cohen's kappa = 0.44 to 0.88).
Conclusions: This is the first study proving similar CIN2 + /CIN3 + sensitivity for FVU-hrHPV testing using the 10-mL Colli-Pee device and Allplex HR HPV assay compared to testing in cervical samples. From an implementation perspective, further research is needed to gather additional clinical accuracy and acceptability data on hrHPV testing of FVU-device collection in under-screened populations to support its broader integration into screening programmes.
Trial registration: Clinicaltrials.gov: NCT05065853.
Keywords: Cervical cancer screening; Early detection of cancer/methods; HrHPV DNA testing; Mass screening; Sensitivity and specificity; Urinary hrHPV testing; Uterine cervical dysplasia.
© 2025. The Author(s).
Conflict of interest statement
Declarations. Ethics approval and consent to participate: The project was listed in the record of processing activities for research projects in the Central Denmark Region (j.no. 1–16-02–313-21) and approved by the Ethics Committee in the Central Denmark Region (j. no: 1–10-72–246-21). All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: Seegene sponsors the Allplex HR HPV assays for the study. According to the contract between Seegene and the University Research Clinic for Cancer Screening and Dept. of Pathology, Randers Regional Hospital, Seegene had no influence on the scientific process and no editorial rights pertaining to this manuscript. The authors retained the right to submit the manuscript. MT and JSJ have participated in other studies with HPV test kits sponsored by Roche. MT has received honoraria fee from Roche Diagnostics and AstraZeneca for lectures on HPV self-sampling and HPV triage-methods, respectively. SVK was supported by a junior postdoctoral fellowship of the Research Foundation – Flanders (grant no: 1240220 N). The University of Antwerp received payment for participation of SVK in an Advisory Board of Novosanis (Subsidiary of OraSure Technologies Inc, Wijnegem, Belgium). All funds are handled and managed by the University of Antwerp. LWG and AH: Have outside this project, received free-of-charge test kits from Roche Diagnostics and AH has received honoraria fee from Exeltis. PN, PB, KOB, and CB: No competing interests. AV: is co-founder of and former board member of Novosanis (Subsidiary of OraSure Technologies Inc, Wijnegem, Belgium), a spin-off company of the University of Antwerp, and was minority shareholder until January 2019.
Figures
References
-
- Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30:F88–99. - PubMed
-
- Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJF, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. The Lancet. 2014;383(9916):524–32. - PubMed
-
- Inturrisi F, Aitken CA, Melchers WJG, van den Brule AJC, Molijn A, Hinrichs JWJ, et al. Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study. Lancet Reg Health Eur. 2021;11: 100235. - PMC - PubMed
-
- Serrano B, Ibáñez R, Robles C, Peremiquel-Trillas P, de Sanjosé S, Bruni L. Worldwide use of HPV self-sampling for cervical cancer screening. Prev Med. 2022;154: 106900. - PubMed
