Clinical and analytical evaluation of the RealTime High Risk HPV assay in Colli-Pee collected first-void urine using the VALHUDES protocol

Abstract

ObjectiveUrine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. MethodsVALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples (NCT03064087). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator.3 ResultsAs no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN≤32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI:0.88-1.01) and specific (relative specificity 1.03; 95% CI:0.95-1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI:0.89-1.05) and specificity (1.02; 95% CI:0.93-1.12) was found. Additionally, an exploratory cut-off (CN≤33.86) was defined which further improved sensitivity and analytical test performance. ConclusionHrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Study Protocol: Randomised Controlled Trial Assessing the Efficacy of Strategies Involving Self-Sampling in Cervical Cancer Screening

“…Several studies have been set up recently that compares the clinical accuracy of HPV testing on diverse types of self-samples (vaginal, first-void urine) with HPV testing on cervical samples taken by a clinician [16,[37][38][39].…”

“…The vaginal and urinary self-samples will be analysed at the virology laboratory of the Angers University Hospital using realtime PCR for the search of oncogenic HPV with extended genotyping (BD Onclarity ™ HPV test, BD Diagnostics, Burlington, NC). The BD Onclarity ™ HPV test provides results for six individual high-risk HPV genotypes (16,18,31,45, 51 and 52), with the remaining eight high-risk genotypes reported in three small groups: (33,58), (35,39,68) and (56, 59, 66). The Onclarity ™ assay fulfills requirements for HPV tests in the context of cervical cancer screening [24,25].…”

“…HPV testing can also be performed on first-void urine [ 15 ], which is less invasive and might be even more acceptable than vaginal self-sampling for women reluctant to undergo gynaecologic examinations. The clinical accuracy of HPV testing on urine and on vaginal samples was investigated in the VALHUDES trial (VALidation of HUman papillomavirus assays and collection DEvices for Self-samples and urine samples) [ 16 ]. However, no data exist today indicating that sending urine collection kits may be more effective than sending vaginal self-collection kits or conventional invitations.…”

False Negative Results in Cervical Cancer Screening—Risks, Reasons and Implications for Clinical Practice and Public Health

“…In order to address still unmet needs in CC screening some novel methods have been proposed. HPV testing on first-void urine samples seems to be an acceptable method for reaching underscreened women, with sensitivity and specificity comparable with respective indicators of HPV test performed on clinician-taken samples [ 185 , 186 ]. HR HPV digital droplet polymerase chain reaction test, based on the fractionation of a sample into droplets and subsequent detection and quantification of HPV DNA in each of them, may improve the sensitivity of HPV detection in CIN lesions and early CC tumors [ 187 , 188 ].…”

Cervical screening: the evolving landscape

“…Another potential sample type for cervical screening is urine, which has advantages in terms of familiarity with self-collection and avoidance of an intimate procedure. Promising diagnostic accuracy for hr-HPV detection 17 and acceptability with users has been reported when urine is collected using a bespoke first void urine collection device called the Colli-Pee (Novosanis, Wijnegem, Belgium). The ACES (Alternative Cervical Screening) suite of studies in Manchester, UK, will establish with precision how urine compares to cervical sampling for cervical precancer detection, and provide proof of principle for home-based urine self-collection with postal return for hr-HPV testing in current cervical screening non-attenders.…”