Cervical cancer; Diagnostic test accuracy; First-void urine; Human papillomavirus; Prevention; Screening; Self-samples; WHO; Oncology; Obstetrics and Gynecology
Abstract :
[en] OBJECTIVE: Human papillomavirus (HPV) testing on self-collected urine and vaginal samples has shown great potential for cervical cancer screening by offering a non-invasive and approachable alternative to un(der)screened populations. Although many HPV tests were validated on cervical samples, data regarding clinical performance on self-samples is warranted prior to its clinical use.
METHODS: The VALHUDES framework was designed to evaluate the accuracy of HPV tests on self-samples. As such, five colposcopy clinics enrolled patients with aberrant cervical results, asking them to collect a first-void urine (Colli-Pee) and a vaginal self-sample (Evalyn Brush or Qvintip). Additionally, a clinician-collected cervical sample was collected as comparator. 0.4 mL of all samples was used for DNA extraction with Abbott m2000, eluting in 50 μL. To detect high-risk HPV, PCR was conducted on 5 μL DNA extract from all samples with the EUROArray HPV test. Disease outcome was determined by colposcopy with or without biopsy. Relative accuracy was estimated for each self-sample type compared to the clinician-collected sample.
RESULTS: Data was available from 491 and 494 matched samples for vaginal and first-void urine self-samples, respectively. Relative sensitivity for CIN2+ was 0.96 (95 % CI: 0.91-1.02) for vaginal self-samples and 0.96 (95 % CI: 0.90-1.05) for first-void urine. The specificity for <CIN2 was also not significantly lower on the self-samples compared to clinician-taken samples (relative specificity: 0.98 [95 % CI: 0.91-1.07] for vaginal self-samples and 0.94 [95 % CI: 0.85-1.04] for first-void urine).
CONCLUSIONS: The accuracy of EUROArray HPV is similar on vaginal self-samples and first-void urine compared to clinician-collected cervical samples.
Disciplines :
Oncology Radiology, nuclear medicine & imaging
Author, co-author :
van den Borst, Eef; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2650 Edegem, Belgium, Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2650 Edegem, Belgium. Electronic address: eef.vandenborst@uantwerpen.be
Vanden Broeck, Davy; Laboratory of Molecular Pathology, AML Sonic Healthcare, Antwerp, Belgium, National Reference Centre for HPV, Brussels, Belgium, AMBIOR, Laboratory for Cell Biology & Histology, University of Antwerp, Antwerp, Belgium, International Centre for Reproductive Health, Ghent University, Ghent, Belgium
De Sutter, Philippe; Department Gynaecology-Oncology, UZ Brussel-VUB, Brussels, Belgium
Donders, Gilbert; Department of Obstetrics and Gynaecology of the General Regional Hospital Heilig Hart, Tienen, Belgium, Femicare vzw, Clinical Research for Women, Tienen, Belgium, Department of Obstetrics and Gynaecology University Hospital Antwerp, Antwerp, Belgium
Doyen, Jean ; Université de Liège - ULiège > Département des sciences de la santé publique
Tjalma, Wiebren; Multidisciplinary Breast Clinic, Unit Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Antwerp University Hospital (UZA), Edegem, Belgium, Molecular Imaging, Pathology, Radiotherapy, Oncology (MIPRO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
Weyers, Steven; Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium
Arbyn, Marc; Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels, Belgium, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, University Ghent, Ghent, Belgium
Van Keer, Severien; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2650 Edegem, Belgium
Latsuzbaia, Ardashel; Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels, Belgium
Language :
English
Title :
EUROArray HPV test accuracy for cervical precancer in self- vs. clinician-collected samples using the VALHUDES protocol.
Publication date :
2025
Journal title :
Gynecologic Oncology
ISSN :
0090-8258
eISSN :
1095-6859
Publisher :
Academic Press Inc., United States
Volume :
202
Pages :
14 - 23
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
UA - University of Antwerp FWO - Research Foundation Flanders EU - European Union
Funding text :
This work was supported by the Industrial Research Fund of the University of Antwerp , Belgium under grant number PS ID 32387. Eef van den Borst is supported by a PhD fellowship of the Research Foundation Flanders (Belgium) (FWO; grant number 1SC9125N ). Marc Arbyn and Ardashel Latsuzbaia were supported by the RISCC Network [grant no. 8478459] funded by the Horizon 2020 Program for Research and Innovation of the European Commission (Brussels, Belgium). Marc Arbyn was supported by the EU Joint Action EUCanScreen (Grant No. 101162959).This work was supported by the Industrial Research Fund of the University of Antwerp, Belgium under grant number PS ID 32387. Eef van den Borst is supported by a PhD fellowship of the Research Foundation Flanders (Belgium) (FWO; grant number 1SC9125N). Marc Arbyn and Ardashel Latsuzbaia were supported by the RISCC Network [grant no. 8478459] funded by the Horizon 2020 Program for Research and Innovation of the European Commission (Brussels, Belgium). Marc Arbyn was supported by the EU Joint Action EUCanScreen (Grant No. 101162959).MA and AL were supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (Grant No. 847845).
Costa, S., Verberckmoes, B., Castle, P.E., Arbyn, M., Offering HPV self-sampling kits: an updated meta-analysis of the effectiveness of strategies to increase participation in cervical cancer screening. Br. J. Cancer 128:5 (Mar 2023), 805–813, 10.1038/s41416-022-02094-w.
Lefeuvre, C., Pivert, A., Guillou-Guillemette, H.L., et al. Urinary HPV DNA testing as a tool for cervical cancer screening in women who are reluctant to have a pap smear in France. J. Inf. Secur. 81:2 (Aug 2020), 248–254, 10.1016/j.jinf.2020.05.006.
Ducancelle, A., Reiser, J., Pivert, A., Le Guillou-Guillemette, H., Le Duc-Banaszuk, A.S., Lunel-Fabiani, F., Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics. J. Inf. Secur. 71:3 (Sep 2015), 377–384, 10.1016/j.jinf.2015.05.001.
Arbyn, M., Smith, S.B., Temin, S., et al. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ, 363, 2018, k4823, 10.1136/bmj.k4823.
World Health Organization, Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. 2020, World Health Organization, 56.
Pathak, N., Dodds, J., Zamora, J., Khan, K., Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis. BMJ, 349, Sep 16 2014, g5264, 10.1136/bmj.g5264.
Arbyn, M., Castle, P.E., Schiffman, M., Wentzensen, N., Heckman-Stoddard, B., Sahasrabuddhe, V.V., Meta-analysis of agreement/concordance statistics in studies comparing self- vs clinician-collected samples for HPV testing in cervical cancer screening. Int. J. Cancer 151:2 (Jul 15 2022), 308–312, 10.1002/ijc.33967.
Vorsters, A., Micalessi, I., Bilcke, J., Ieven, M., Bogers, J., Van Damme, P., Detection of human papillomavirus DNA in urine. A review of the literature. Eur. J. Clin. Microbiol. Infect. Dis. 31:5 (May 2012), 627–640, 10.1007/s10096-011-1358-z.
Vorsters, A., Van den Bergh, J., Micalessi, I., et al. Optimization of HPV DNA detection in urine by improving collection, storage, and extraction. Eur. J. Clin. Microbiol. Infect. Dis. 33:11 (Nov 2014), 2005–2014, 10.1007/s10096-014-2147-2.
zur Hausen, H., Condylomata acuminata and human genital cancer. Cancer Res., 36(2 pt 2), 1976, 794.
Koliopoulos, G., Nyaga, V.N., Santesso, N., et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst. Rev., 8(8), 2017, CD008587, 10.1002/14651858.CD008587.pub2.
Ronco, G., Dillner, J., Elfstrom, K.M., et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 383:9916 (2014), 524–532, 10.1016/S0140-6736(13)62218-7.
Arbyn, M., Ronco, G., Anttila, A., et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 30:Suppl. 5 (2012 Nov 20), F88–F99, 10.1016/j.vaccine.2012.06.095.
Arbyn, M., Peeters, E., Benoy, I., et al. VALHUDES: a protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples. J. Clin. Virol. 107 (Oct 2018), 52–56, 10.1016/j.jcv.2018.08.006.
Arbyn, M., Verdoodt, F., Snijders, P.J., et al. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 15:2 (2014), 172–183, 10.1016/S1470-2045(13)70570-9.
Van Keer, S., Peeters, E., Vanden Broeck, D., et al. Clinical and analytical evaluation of the RealTime high risk HPV assay in Colli-pee collected first-void urine using the VALHUDES protocol. Gynecol. Oncol. 162:3 (Sep 2021), 575–583, 10.1016/j.ygyno.2021.06.010.
Latsuzbaia, A., Vanden Broeck, D., Van Keer, S., et al. Clinical performance of the RealTime high risk HPV assay on self-collected vaginal samples within the VALHUDES framework. Microbiol. Spectr., 10(5), Oct 26 2022, e0163122, 10.1128/spectrum.01631-22.
Latsuzbaia, A., Van Keer, S., Vanden Broeck, D., et al. Clinical accuracy of Alinity m HR HPV assay on self- versus clinician-taken samples using the VALHUDES protocol. J. Mol. Diagn. 25:12 (Dec 2023), 957–966, 10.1016/j.jmoldx.2023.09.008.
Latsuzbaia, A., Vanden Broeck, D., Van Keer, S., et al. Validation of BD Onclarity HPV assay on vaginal self-samples versus cervical samples using the VALHUDES protocol. Cancer Epidemiol. Biomarkers Prev. 31:12 (Dec 5 2022), 2177–2184, 10.1158/1055-9965.EPI-22-0757.
Van Keer, S., Latsuzbaia, A., Vanden Broeck, D., et al. Analytical and clinical performance of extended HPV genotyping with BD Onclarity HPV assay in home-collected first-void urine: a diagnostic test accuracy study. J. Clin. Virol., 155, Oct 2022, 105271, 10.1016/j.jcv.2022.105271.
Latsuzbaia, A., Vanden Broeck, D., Van Keer, S., et al. Comparison of the clinical accuracy of Xpert HPV assay on vaginal self-samples and cervical clinician-taken samples within the VALHUDES framework. J. Mol. Diagn. 25:9 (Sep 2023), 702–708, 10.1016/j.jmoldx.2023.06.004.
Latsuzbaia, A., Van Keer, S., Broeck, D.V., et al. Accuracy of Liferiver HarmoniaHPV and VenusHPV assays on urine and vaginal self-samples. J. Med. Virol., 97(3), 2025, e70273, 10.1002/jmv.70273.
Van Keer, S., Latsuzbaia, A., Broeck, D.V., et al. Equivalent clinical accuracy of human papillomavirus DNA testing using cobas 4800 and 6800 human papillomavirus systems in paired urine and cervical samples. J. Mol. Diagn., 2025, 10.1016/j.jmoldx.2025.02.004.
Viti, J., Poljak, M., Ostrbenk, A., et al. Validation of EUROArray HPV test using the VALGENT framework. J. Clin. Virol. 108 (Nov 2018), 38–42, 10.1016/j.jcv.2018.09.005.
Arbyn, M., Simon, M., Peeters, E., et al. 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clin. Microbiol. Infect. 27:8 (Aug 2021), 1083–1095, 10.1016/j.cmi.2021.04.031.
BE 71030031000, Biobank Antwerp [BB190007] BBMR-ERIC. Belgian, [BIORESOURCE], 2025.
Serrano, B., Ibanez, R., Robles, C., Peremiquel-Trillas, P., de Sanjose, S., Bruni, L., Worldwide use of HPV self-sampling for cervical cancer screening. Prev. Med., 154, Jan 2022, 106900, 10.1016/j.ypmed.2021.106900.
Cadman, L., Reuter, C., Jitlal, M., et al. A randomized comparison of different vaginal self-sampling devices and urine for human papillomavirus testing-predictors 5.1. Cancer Epidemiol. Biomarkers Prev. 30:4 (Apr 2021), 661–668, 10.1158/1055-9965.EPI-20-1226.
Jordaens, S., Zwaenepoel, K., Tjalma, W., et al. Urine biomarkers in cancer detection: a systematic review of preanalytical parameters and applied methods. Int. J. Cancer 152:10 (May 15 2023), 2186–2205, 10.1002/ijc.34434.
Poljak, M., Cuschieri, K., Alemany, L., Vorsters, A., Testing for human papillomaviruses in urine, blood, and oral specimens: an update for the laboratory. J. Clin. Microbiol., 61(8), Aug 23 2023, e0140322, 10.1128/jcm.01403-22.
Arbyn, M., Costa, S., Latsuzbaia, A., et al. HPV-based cervical cancer screening on self-samples in the netherlands: challenges to reach women and test performance questions. Cancer Epidemiol. Biomarkers Prev. 32:2 (Feb 6 2023), 159–163, 10.1158/1055-9965.EPI-22-1041.
Latsuzbaia, A., Martinelli, M., Giubbi, C., et al. Clinical accuracy of OncoPredict HPV quantitative typing (QT) assay on self-samples. J. Clin. Virol., 175, Dec 2024, 105737, 10.1016/j.jcv.2024.105737.
Rohner, E., Rahangdale, L., Sanusi, B., et al. Test accuracy of human papillomavirus in urine for detection of cervical intraepithelial neoplasia. J. Clin. Microbiol., 58(3), Feb 24 2020, 10.1128/JCM.01443-19.
World Health Organization, Human papillomavirus vaccines: WHO position paper (2022 update). Wkly Epidemiol. Rec. 97:50 (2022), 645–672 16–12-2022.
IARC, IARC Handbooks of Cancer Prevention: Cervical Cancer Screening. 18, 2022.
Wei, F., Georges, D., Man, I., Baussano, I., Clifford, G.M., Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: a systematic analysis of the global literature. Lancet 404:10451 (Aug 3 2024), 435–444, 10.1016/S0140-6736(24)01097-3.
Cornall, A.M., Poljak, M., Garland, S.M., et al. Anyplex II HPV28 detection and Anyplex II HPV HR detection assays are highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities. Eur. J. Clin. Microbiol. Infect. Dis. 36:3 (Mar 2017), 545–551, 10.1007/s10096-016-2831-5.
Cornall, A.M., Poljak, M., Garland, S.M., et al. EUROarray human papillomavirus (HPV) assay is highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities. Eur. J. Clin. Microbiol. Infect. Dis. 35:6 (Jun 2016), 1033–1036, 10.1007/s10096-016-2634-8.
Latsuzbaia, A., Tapp, J., Nguyen, T., et al. Analytical performance evaluation of Anyplex II HPV28 and Euroarray HPV for genotyping of cervical samples. Diagn. Microbiol. Infect. Dis. 85:3 (Jul 2016), 318–322, 10.1016/j.diagmicrobio.2016.04.011.
Brentnall, A.R., Cuschieri, K., Sargent, A., Berkhof, J., Rebolj, M., Staged design recommendations for validating relative sensitivity of self-sample human papillomavirus tests for cervical screening. J. Clin. Epidemiol., 166, Feb 2024, 111227, 10.1016/j.jclinepi.2023.111227.
