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

Alex Sargent, Samantha Fletcher, Katarina Bray, Henry C Kitchener, Emma J Crosbie, Alex Sargent, Samantha Fletcher, Katarina Bray, Henry C Kitchener, Emma J Crosbie

Abstract

Objectives: Human papillomavirus (HPV) testing in cervical screening offers the potential for self-sampling to improve uptake among non-attenders. High-risk (HR) HPV detection in urine shows promise, but few studies have examined its sensitivity for cervical intraepithelial neoplasia (CIN2+) detection compared with standard cervical samples. The aims of this cross-sectional study were to optimise conditions for urine testing for HPV detection; to determine concordance for HR-HPV detection in matched urine, vaginal and cervical samples; to compare the sensitivity of HR-HPV testing for the detection of CIN2+ in matched samples; and to determine the acceptability of urine testing for cervical screening.

Design: Cross-sectional study.

Setting: Secondary care colposcopy clinic in North West England.

Participants: Women aged 25 years of age or older, attending colposcopy clinic for management of abnormal cervical screening results or a suspicious-looking cervix. In total, 104 women took part in the study. Triple matched samples were available for 79 and 66 women using Abbott RealTime (ART) and Roche Cobas 4800 (RC), respectively.

Intervention: Self-collected urine and vaginal samples and practitioner-obtained cervical samples were tested for HR-HPV by ART and RC assays, including comparison of neat and preservative-fixed urine. Colposcopic opinion was recorded and directed cervical biopsies taken if clinically indicated. The acceptability of self-testing was evaluated by questionnaire.

Primary outcome measure: The sensitivity of urine to detect underlying CIN2+.

Secondary outcome measures: The comparative sensitivity of vaginal and cervical samples to detect CIN2+; the acceptability of urine sampling.

Results: Preservative-fixed, but not neat urine, showed good concordance with vaginal samples for the detection of HR-HPV. The sensitivity for detecting CIN2+ was 15/18 (83%) for urine and 16/18 (89%) for cervical and vaginal samples by ART, and 15/17 (88%) for all samples by RC. Urine-based testing was broadly acceptable to women.

Conclusions: Urinary HR-HPV detection offers an alternative strategy of cervical screening. Larger studies to determine its clinical utility are warranted.

Keywords: Urinary human papillomavirus (HPV) detection; acceptability; cervical cancer screening; cervical intraepithelial neoplasia (CIN).

Conflict of interest statement

Competing interests: HCK is Chair of the Advisory Committee for Cervical Screening (PHE), but the views expressed in this manuscript are those of the author and not Public Health England.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Demographics of study participants and reasons for declining participation. CIN2+, cervical intraepithelial neoplasia grade 2+; GCSE, General Certificate of Secondary Education; PG, postgraduate; UG, undergraduate.
Figure 2
Figure 2
A comparison of the mean ct values for detection of the internal beta globin control and HR-HPV in urine, vaginal and cervical samples using the ART (A,B) and RC assays (C,D). ct, cycle threshold; HPV, human papillomavirus.
Figure 3
Figure 3
The acceptability of urine and vaginal self-obtained samples for cervical screening.

References

    1. Crosbie EJ, Einstein MH, Franceschi S, et al. . Human papillomavirus and cervical cancer. Lancet 2013;382:889–99. 10.1016/S0140-6736(13)60022-7
    1. Kitchener HC, Denton K, Soldan K, et al. . Developing role of HPV in cervical cancer prevention. BMJ 2013;347:f4781 10.1136/bmj.f4781
    1. Ronco G, Dillner J, Elfström KM, et al. . Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;383:524–32. 10.1016/S0140-6736(13)62218-7
    1. Waller J, Bartoszek M, Marlow L, et al. . Barriers to cervical cancer screening attendance in England: a population-based survey. J Med Screen 2009;16:199–204. 10.1258/jms.2009.009073
    1. Kitchener HC, Gittins M, Rivero-Arias O, et al. . A cluster randomised trial of strategies to increase cervical screening uptake at first invitation (STRATEGIC). Health Technol Assess 2016;20:1–138. 10.3310/hta20680
    1. Verdoodt F, Jentschke M, Hillemanns P, et al. . Reaching women who do not participate in the regular cervical cancer screening programme by offering self-sampling kits: a systematic review and meta-analysis of randomised trials. Eur J Cancer 2015;51:2375–85. 10.1016/j.ejca.2015.07.006
    1. Polman NJ, Ebisch RMF, Heideman DAM, et al. . Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial. Lancet Oncol 2019;20:229–38. 10.1016/S1470-2045(18)30763-0
    1. Stanczuk G, Baxter G, Currie H, et al. . 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 2016;6:e010660 10.1136/bmjopen-2015-010660
    1. Pathak N, Dodds J, Zamora J, et al. . Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis. BMJ 2014;349:g5264 10.1136/bmj.g5264
    1. Kitchener HC, Owens GL. Urine Testing for HPV. A promising screening option that deserves further evaluation. BMJ 2014;349:g5542.
    1. Blake DA, Crosbie EJ, Kitson S. Urinary HPV testing may offer hope for cervical screening non-attenders. BJOG 2017. 124:1364 10.1111/1471-0528.14683
    1. Johnson DJ, Calderaro AC, Roberts KA. Variation in nuclear DNA concentrations during urination. J Forensic Sci 2007;52:110–3. 10.1111/j.1556-4029.2006.00329.x
    1. 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 2014;33:2005–14. 10.1007/s10096-014-2147-2
    1. Heideman DA, Hesselink AT, Berkhof J, et al. . Clinical validation of the cobas 4800 HPV test for cervical screening purposes. J Clin Microbiol 2011;49:3983–5. 10.1128/JCM.05552-11
    1. Poljak M, Ostrbenk A, Seme K, et al. . Comparison of clinical and analytical performance of the Abbott Realtime High Risk HPV test to the performance of hybrid capture 2 in population-based cervical cancer screening. J Clin Microbiol 2011;49:1721–9. 10.1128/JCM.00012-11
    1. Moss SM, Bailey A, Cubie H, et al. . Comparison of the performance of HPV tests in women with abnormal cytology: results of a study within the NHS cervical screening programme. Cytopathology 2015;26:373–80. 10.1111/cyt.12210
    1. Daponte A, Pournaras S, Mademtzis I, et al. . Evaluation of high-risk human papillomavirus types PCR detection in paired urine and cervical samples of women with abnormal cytology. J Clin Virol 2006;36:189–93. 10.1016/j.jcv.2006.03.009
    1. Daponte A, Tsezou A, Oikonomou P, et al. . Use of real-time PCR to detect human papillomavirus-16 viral loads in vaginal and urine self-sampled specimens. Clin Microbiol Infect 2008;14:619–21. 10.1111/j.1469-0691.2008.01974.x
    1. Szarewski A, Cadman L, Mesher D, et al. . HPV self-sampling as an alternative strategy in non-attenders for cervical screening - a randomised controlled trial. Br J Cancer 2011;104:915–20. 10.1038/bjc.2011.48

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren