Equivalent Clinical Accuracy of Human Papillomavirus DNA Testing Using Cobas 4800 and 6800 Human Papillomavirus Systems in Paired Urine and Cervical Samples.
Van Keer, Severien; Latsuzbaia, Ardashel; Vanden Broeck, Davyet al.
2025 • In Journal of Molecular Diagnostics, 27 (5), p. 419 - 429
DNA, Viral; Adult; Female; Humans; Middle Aged; Colposcopy; Early Detection of Cancer/methods; Human Papillomavirus Viruses; Sensitivity and Specificity; Uterine Cervical Dysplasia/diagnosis; Uterine Cervical Dysplasia/virology; Cervix Uteri/virology; Cervix Uteri/pathology; DNA, Viral/genetics; DNA, Viral/urine; Human Papillomavirus DNA Tests/methods; Papillomaviridae/genetics; Papillomavirus Infections/diagnosis; Papillomavirus Infections/urine; Papillomavirus Infections/virology; Uterine Cervical Neoplasms/diagnosis; Uterine Cervical Neoplasms/virology; Uterine Cervical Neoplasms/urine; Pathology and Forensic Medicine; Molecular Medicine
Abstract :
[en] The use of urine for cervical cancer screening is gaining international attention, although more data on the relative clinical accuracy of validated human papillomavirus (HPV) DNA tests on urine versus cervical samples are needed. This study primarily seeks to evaluate the clinical performance of Roche cobas 4800 and 6800 HPV Systems in first-void urine, collected at home, compared with clinician-collected cervical samples. Paired first-void urine (index test) and cervical samples (comparator test) from 499 females enrolled at five Belgian colposcopy clinics were analyzed with cobas HPV Systems. Colposcopy and histology of biopsies were used as reference test (trial registration number: NCT03064087). Sample processing protocols and clinical thresholds proposed by the manufacturer for cervical samples were also applied for first-void urine. In the total study population, HPV testing on first-void urine was similarly sensitive [ratioCIN2+, 0.98; 95% CI, 0.93-1.02] and specific for cobas 4800 HPV (ratio<CIN2, 1.00; 95% CI, 0.91-1.10) and cobas HPV for use on the cobas 6800 System (ratioCIN2+, 0.96; 95% CI, 0.91-1.02; ratio<CIN2, 1.01; 95% CI, 0.93-1.09) compared with cervical samples (P ≥ 0.05). Good to excellent HPV test agreements between paired samples were observed (κ = 0.68 to 0.87). In summary, HPV testing using cobas 4800 and 6800 HPV Systems was as accurate on first-void urine as on cervical samples collected by a clinician.
Disciplines :
Oncology
Author, co-author :
Van Keer, Severien ; Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Edegem, Belgium. Electronic address: severien.vankeer@uantwerpen.be
Latsuzbaia, Ardashel; Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels, Belgium
Vanden Broeck, Davy ; Laboratory of Molecular Pathology, AML Sonic Healthcare, Antwerp, Belgium, National Reference Centre for HPV, Brussels, Belgium, AMBIOR, Laboratory for Cell Biology and Histology, University of Antwerp, Wilrijk (Antwerp), Belgium, International Centre for Reproductive Health, Ghent University, Ghent, Belgium
De Sutter, Philippe; Department Gynaecology-Oncology, University Hospital Brussels-Vrije Universiteit Brussel, Jette (Brussels), Belgium
Donders, Gilbert; Department of Obstetrics and Gynaecology, General Regional Hospital Heilig Hart, Tienen, Belgium, Femicare vzw, Clinical Research for Women, Tienen, Belgium, Department of Obstetrics and Gynaecology, Antwerp University Hospital, Edegem, Belgium
Doyen, Jean ; Université de Liège - ULiège > Département des sciences de la santé publique
Tjalma, Wiebren A A; Multidisciplinary Breast Clinic, Unit Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Antwerp University Hospital, Edegem, Belgium, Molecular Imaging, Pathology, Radiotherapy, Oncology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium
Weyers, Steven; Department of Obstetrics and Gynecology, 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, Ghent University, Ghent, Belgium
Vorsters, Alex ; Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Edegem, Belgium
Language :
English
Title :
Equivalent Clinical Accuracy of Human Papillomavirus DNA Testing Using Cobas 4800 and 6800 Human Papillomavirus Systems in Paired Urine and Cervical Samples.
Publication date :
2025
Journal title :
Journal of Molecular Diagnostics
ISSN :
1525-1578
eISSN :
1943-7811
Publisher :
Elsevier, United States
Volume :
27
Issue :
5
Pages :
419 - 429
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
UA - University of Antwerp FWO - Flemish Research Foundation
Funding text :
This work was supported by the Industrial Research Fund of the University of Antwerp, Belgium under grant number PS ID 32387. Severien Van Keer was supported by a junior postdoctoral fellowship of the Research Foundation \u2013 Flanders (FWO), Belgium under grant number 1240220N. Marc Arbyn and Ardashel Latsuzbaia are supported by the RISCC Network funded by the Horizon 2020 Framework of DG Research and Innovation, European Commission, Brussels, Belgium (grant No. 847845); and a SME Instrument Grant GA 80551, funded by the Horizon 2020 program of DG Research and Innovation, European Commission, Brussels, Belgium.
WHO. Global strategy to accelerate the elimination of cervical cancer as a public health problem. 2020, World Health Organization, Geneva, Switzerland.
zur Hausen, H., Papillomaviruses in the causation of human cancers—a brief historical account. Virology 384 (2009), 260–265.
Ronco, G., Dillner, J., Elfstrom, K.M., Tunesi, S., Snijders, P.J., Arbyn, M., Kitchener, H., Segnan, N., Gilham, C., Giorgi-Rossi, P., Berkhof, J., Peto, J., Meijer, C.J., International HPV Screening Working Group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 383 (2014), 524–532.
Arbyn, M., Ronco, G., Anttila, A., Meijer, C.J., Poljak, M., Ogilvie, G., Koliopoulos, G., Naucler, P., Sankaranarayanan, R., Peto, J., Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 30:Suppl 5 (2012), F88–F99.
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 (2022), 308–312.
Arbyn, M., Smith, S.B., Temin, S., Sultana, F., Castle, P., Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ, 363, 2018, k4823.
Arbyn, M., Verdoodt, F., Snijders, P.J., Verhoef, V.M., Suonio, E., Dillner, L., Minozzi, S., Bellisario, C., Banzi, R., Zhao, F.H., Hillemanns, P., Anttila, A., Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol 15 (2014), 172–183.
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 (2023), 805–813.
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, 2014, g5264.
Leeman, A., Del Pino, M., Molijn, A., Rodriguez, A., Torne, A., de Koning, M., Ordi, J., van Kemenade, F., Jenkins, D., Quint, W., HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population. BJOG 124 (2017), 1356–1363.
Rohner, E., McGuire, F.H., Liu, Y., Li, Q., Miele, K., Desai, S.A., Schmitt, J.W., Knittel, A., Nelson, J.A.E., Edelman, C., Sivaraman, V., Baker, A., Romocki, L.S., Rahangdale, L., Smith, J.S., Racial and ethnic differences in acceptability of urine and cervico-vaginal sample self-collection for HPV-based cervical cancer screening. J Womens Health (Larchmt) 29 (2020), 971–979.
Sellors, J.W., Lorincz, A.T., Mahony, J.B., Mielzynska, I., Lytwyn, A., Roth, P., Howard, M., Chong, S., Daya, D., Chapman, W., Chernesky, M., Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions. CMAJ 163 (2000), 513–518.
Senkomago, V., Des Marais, A.C., Rahangdale, L., Vibat, C.R., Erlander, M.G., Smith, J.S., Comparison of urine specimen collection times and testing fractions for the detection of high-risk human papillomavirus and high-grade cervical precancer. J Clin Virol 74 (2016), 26–31.
Sargent, A., Fletcher, S., Bray, K., Kitchener, H.C., Crosbie, E.J., Cross-sectional study of HPV testing in self-sampled urine and comparison with matched vaginal and cervical samples in women attending colposcopy for the management of abnormal cervical screening. BMJ Open, 9, 2019, e025388.
Tranberg, M., Jensen, J.S., Bech, B.H., Andersen, B., Urine collection in cervical cancer screening - analytical comparison of two HPV DNA assays. BMC Infect Dis, 20, 2020, 926.
De Pauw, H., Donders, G., Weyers, S., De Sutter, P., Doyen, J., Tjalma, W.A.A., Vanden Broeck, D., Peeters, E., Van Keer, S., Vorsters, A., Arbyn, M., Cervical cancer screening using HPV tests on self-samples: attitudes and preferences of women participating in the VALHUDES study. Arch Public Health, 79, 2021, 155.
Lefeuvre, C., Pivert, A., Guillou-Guillemette, H.L., Lunel-Fabiani, F., Veillon, P., Le Duc-Banaszuk, A.S., Ducancelle, A., Urinary HPV DNA testing as a tool for cervical cancer screening in women who are reluctant to have a Pap smear in France. J Infect 81 (2020), 248–254.
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 Infect 71 (2015), 377–384.
Ørnskov, D., Jochumsen, K., Steiner, P.H., Grunnet, I.M., Lykkebo, A.W., Waldstrom, M., Clinical performance and acceptability of self-collected vaginal and urine samples compared with clinician-taken cervical samples for HPV testing among women referred for colposcopy: a cross-sectional study. BMJ Open, 11, 2021, e041512.
Latsuzbaia, A., Van Keer, S., Vanden Broeck, D., Weyers, S., Donders, G., De Sutter, P., Tjalma, W., Doyen, J., Vorsters, A., Arbyn, M., Clinical accuracy of alinity m HR HPV assay on self- versus clinician-taken samples using the VALHUDES protocol. J Mol Diagn 25 (2023), 957–966.
Van Keer, S., Latsuzbaia, A., Vanden Broeck, D., De Sutter, P., Donders, G., Doyen, J., Tjalma, W.A.A., Weyers, S., Arbyn, M., Vorsters, A., 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, 2022, 105271.
Van Keer, S., Peeters, E., Vanden Broeck, D., De Sutter, P., Donders, G., Doyen, J., Tjalma, W.A.A., Weyers, S., Vorsters, A., Arbyn, M., 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 (2021), 575–583.
Martinelli, M., Giubbi, C., Di Meo, M.L., Perdoni, F., Musumeci, R., Leone, B.E., Fruscio, R., Landoni, F., Cocuzza, C.E., Accuracy of human papillomavirus (HPV) testing on urine and vaginal self-samples compared to clinician-collected cervical sample in women referred to colposcopy. Viruses, 15, 2023, 1889.
Davies, J.C., Sargent, A., Pinggera, E., Carter, S., Gilham, C., Sasieni, P., Crosbie, E.J., Urine high-risk human papillomavirus testing as an alternative to routine cervical screening: a comparative diagnostic accuracy study of two urine collection devices using a randomised study design trial. BJOG 131 (2024), 1456–1464.
Poljak, M., Oštrbenk Valenčak, A., Cuschieri, K., Bohinc, K.B., Arbyn, M., 2023 Global inventory of commercial molecular tests for human papillomaviruses (HPV). J Clin Virol, 172, 2024, 105671.
Arbyn, M., Simon, M., Peeters, E., Xu, L., Meijer, C., Berkhof, J., Cuschieri, K., Bonde, J., Ostrbenk Vanlencak, A., Zhao, F.H., Rezhake, R., Gultekin, M., Dillner, J., de Sanjosé, S., Canfell, K., Hillemanns, P., Almonte, M., Wentzensen, N., Poljak, M., 2020 List of human papillomavirus assays suitable for primary cervical cancer screening. Clin Microbiol Infect 27 (2021), 1083–1095.
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, 2023, e0140322.
Arbyn, M., Peeters, E., Benoy, I., Vanden Broeck, D., Bogers, J., De Sutter, P., Donders, G., Tjalma, W., Weyers, S., Cuschieri, K., Poljak, M., Bonde, J., Cocuzza, C., Zhao, F.H., Van Keer, S., Vorsters, A., 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 (2018), 52–56.
Saville, M., Sultana, F., Malloy, M.J., Velentzis, L.S., Caruana, M., Ip, E.L.O., Keung, M.H.T., Canfell, K., Brotherton, J.M.L., Hawkes, D., Clinical validation of the cobas HPV test on the cobas 6800 system for the purpose of cervical screening. J Clin Microbiol, 57, 2019, e01239-18.
Heideman, D.A., Hesselink, A.T., Berkhof, J., van Kemenade, F., Melchers, W.J., Daalmeijer, N.F., Verkuijten, M., Meijer, C.J., Snijders, P.J., Clinical validation of the cobas 4800 HPV test for cervical screening purposes. J Clin Microbiol 49 (2011), 3983–3985.
Frayle, H., Gori, S., Rizzi, M., Graziani, B.N., Vian, E., Giorgi Rossi, P., Del Mistro, A., HPV testing for cervical cancer screening: technical improvement of laboratory logistics and good clinical performance of the cobas 6800 in comparison to the 4800 system. BMC Womens Health, 19, 2019, 47.
Ejegod, D.M., Hansen, M., Christiansen, I.K., Pedersen, H., Quint, W., Xu, L., Arbyn, M., Bonde, J., Clinical validation of the Cobas 4800 HPV assay using cervical samples in SurePath medium under the VALGENT4 framework. J Clin Virol, 128, 2020, 104336.
Altman, D.G., Practical Statistics for Medical Research. 1991, Chapman & Hall/CRC, London, UK.
Bornstein, J., Bentley, J., Bösze, P., Girardi, F., Haefner, H., Menton, M., Perrotta, M., Prendiville, W., Russell, P., Sideri, M., Strander, B., Tatti, S., Torne, A., Walker, P., 2011 Colposcopic terminology of the international federation for cervical pathology and colposcopy. Obstet Gynecol 120 (2012), 166–172.
Jordan, J., Arbyn, M., Martin-Hirsch, P., Schenck, U., Baldauf, J.J., Da Silva, D., Anttila, A., Nieminen, P., Prendiville, W., European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1. Cytopathology 19 (2008), 342–354.
Van Keer, S., Téblick, L., Donders, G., Weyers, S., Doyen, J., Cornelis, A., Van de Vijver, K., Delbecque, K., De Smet, A., Van Damme, P., Vorsters, A., Clinical and analytical evaluation of the Abbott alinity m HR HPV assay in a new generation first-void urine collector. J Med Virol, 97, 2025, e70254.
Lim, M.C., Lee, D.H., Hwang, S.H., Hwang, N.R., Lee, B., Shin, H.Y., Jun, J.K., Yoo, C.W., Lee, D.O., Seo, S.S., Park, S.Y., Joo, J., Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples. J Virol Methods 243 (2017), 74–79.
Cho, H.W., Ouh, Y.T., Hong, J.H., Min, K.J., So, K.A., Kim, T.J., Paik, E.S., Lee, J.W., Moon, J.H., Lee, J.K., Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV assay. J Virol Methods 269 (2019), 77–82.
Hwang, S.H., Shin, H.Y., Lee, D.O., Sung, N.Y., Lee, B., Lee, D.H., Jun, J.K., A prospective pilot evaluation of vaginal and urine self-sampling for the Roche cobas 4800 HPV test for cervical cancer screening. Sci Rep, 8, 2018, 9015.
Yamazaki, H., Wada, T., Asano, H., Fujita, H., Okamoto, K., Watari, H., Comparison between urine and cervical high-risk HPV tests for Japanese women with ASC-US. Diagnostics (Basel), 11, 2021, 1895.
Nilyanimit, P., Chaithongwongwatthana, S., Oranratanaphan, S., Poudyal, N., Excler, J.L., Lynch, J., Vongpunsawad, S., Poovorawan, Y., Comparable detection of HPV using real-time PCR in paired cervical samples and concentrated first-stream urine collected with Colli-Pee device. Diagn Microbiol Infect Dis, 108, 2024, 116160.
Hajjar, B.J., Raheel, U., Manina, R., Simpson, J., Irfan, M., Waheed, Y., Clinical performance of cobas 6800 for the detection of high-risk human papillomavirus in urine samples. Vaccines (Basel), 11, 2023, 1071.
Stanczuk, G.A., Currie, H., Baxter, G., Foster, A., Gibson, L., Graham, C., Cuschieri, K., Cobas 4800 HPV detection in the cervical, vaginal and urine samples of women with high-grade CIN before and after treatment. J Clin Pathol 68 (2015), 567–570.
Stanczuk, G., Baxter, G., Currie, H., Lawrence, J., Cuschieri, K., Wilson, A., Arbyn, M., Clinical validation of hrHPV testing on vaginal and urine self-samples in primary cervical screening (cross-sectional results from the Papillomavirus Dumfries and Galloway-PaVDaG study). BMJ Open, 6, 2016, e010660.
Bernal, S., Palomares, J.C., Artura, A., Parra, M., Cabezas, J.L., Robles, A., Mazuelos, E.M., Comparison of urine and cervical samples for detecting human papillomavirus (HPV) with the Cobas 4800 HPV test. J Clin Virol 61 (2014), 548–552.
Asciutto, K.C., Henningsson, A.J., Borgfeldt, H., Darlin, L., Borgfeldt, C., Vaginal and urine self-sampling compared to cervical sampling for HPV-testing with the cobas 4800 HPV test. Anticancer Res 37 (2017), 4183–4187.
Terada, N., Matsuura, M., Kurokawa, S., Nishimura, Y., Tamate, M., Isoyama, K., Yamazaki, S., Shimada, H., Suzuki, M., Tabuchi, Y., Teramoto, M., Saito, T., Human papillomavirus testing and cytology using physician-collected uterine cervical samples vs. self-collected vaginal samples and urine samples. Int J Clin Oncol 27 (2022), 1742–1749.
Teblick, L., Van Keer, S., De Smet, A., Van Damme, P., Laeremans, M., Rios Cortes, A., Beyers, K., Vankerckhoven, V., Matheeussen, V., Mandersloot, R., Floore, A., Meijer, C., Steenbergen, R.D.M., Vorsters, A., Impact of collection volume and DNA extraction method on the detection of biomarkers and HPV DNA in first-void urine. Molecules, 26, 2021, 1989.
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 (2012), 627–640.
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, 2024, 111227.
Lefeuvre, C., De Pauw, H., Le Duc Banaszuk, A.S., Pivert, A., Ducancelle, A., Rexand-Galais, F., Arbyn, M., Study protocol: randomised controlled trial assessing the efficacy of strategies involving self-sampling in cervical cancer screening. Int J Public Health, 67, 2022, 1604284.
