Urine self-sampling: An Alternative CErvical Screening (ACES) strategy

Abstract

Abstract Background: Cervical screening saves lives but only 68.7% of those eligible in the UK attend. The main barriers include restricted access to screening appointments and poor acceptability of the speculum examination. Urine human papillomavirus (HPV) testing shows promise as an alternative cervical screening strategy and may be an attractive option for non-attenders, including those from the LGBTQ+ community. Key to the introduction of urine based cervical screening is establishing its diagnostic test accuracy and acceptability to the cervical screening population. Aims: The aim of the Alternative CErvical Screening (ACES) studies were to (1) determine the clinical performance of optimised urine HPV testing for CIN2+ detection in colposcopy referral, test of cure and general screening populations; and (2) ascertain its acceptability to the cervical screening population, including people from LGBTQ+ backgrounds. Methods: Matched same-day urine and cervical samples were collected from colposcopy referral, test of cure and general screening populations. In ACES Colposcopy, participants were randomised to provide a first void urine sample using either a standard urine collection pot or the Colli-Pee 10ml device with preservative (DNA Genotek Inc., Ottawa, Canada). In ACES Test of Cure and ACES Primary Care, urine samples were collected with the Colli-PeeTM. All samples were tested for high-risk HPV using Roche Cobas® 8800 at cervical thresholds. HPV positive cervical samples underwent reflex cytology, followed by colposcopy referral, biopsy and treatment as appropriate. We measured sensitivity and specificity relative to cervical samples for cervical intraepithelial neoplasia grade 2 or above (CIN2+) detection. We assessed concurrent acceptability of urine self-sampling in trial participants and prospective acceptability in people from the LGBTQ+ community using a mixed methods approach (survey and qualitative interviews). Results: In total, 465 colposcopy (standard pot n=230, Colli-Pee n=235), 1517 primary care and 448 test of cure participants provided matched cervix and urine samples (total n=2430). Their median age was 35.0 years (IQR 29-44) and 75.2% were of white ethnicity. In ACES Colposcopy, urine HPV test sensitivity for CIN2+ detection was higher with the Colli-Pee (90.3%, 95%CI=83.7-94.9, 112/124) than the standard pot (73.4%, 95%CI=64.7-80.9, 91/124, p=0.0005). Overall, Colli-Pee collected HPV-tested urine was non-inferior for the detection of CIN2+, with a relative sensitivity of 92% (95%CI=0.87-0.97, ACES Colposcopy, n=124 CIN2+ samples in Colli-Pee arm) and a relative specificity of 97% (95% CI: 0.95-0.99; ACES Primary Care, n=1492 CIN2- samples) compared to cervical samples. In ACES Test of Cure, HPV concordance between urine and cervical samples revealed substantial agreement (κ: 0.64, 95% CI: 0.56–0.71). Concurrent acceptability for urine based cervical screening was good with 70% of participants indicating they would be happy to use only a urine sample in the future. When asked about specific future sampling method preference, 31.3% chose urine self-sampling, 36.6% a healthcare-provider taken sample and 32.1% gave no preference. Prospective acceptability of self-sampling methods (vaginal and urine) in the LGBTQ+ community was assessed using a survey. Self-sampling methods were preferred for future cervical screening (72%) with urine most popular (41.7%) particularly amongst transgender individuals (56.2%). Qualitative interviews revealed significant barriers to cervical screening for the transgender male and non-binary community. At home, self- sampling options would likely improve uptake by removing most barriers through enhanced choice of location and sampling method. Conclusion: The Colli-pee urine self-sampling / Roche Cobas® workflow shows non-inferior diagnostic test accuracy for CIN2+ detection compared to routine cervical screening, meeting HPValidate criteria for a candidate self-sample/ HPV testing workflow for NHS implementation. Urine is generally acceptable especially to marginalised groups like the LGBTQ+ community. Urine self-sampling may improve attendance in current non-attenders, however, this must now be formally tested, including how best to offer self-sampling.

Date of Award	14 May 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Tanya Walsh (Co Supervisor), Alexandra Sargent (Co Supervisor) & Emma Davidson (Main Supervisor)