Test Accuracy of Human Papillomavirus in Urine for Detection of Cervical Intraepithelial Neoplasia

Abstract

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triple-matched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urine-based hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care.

Self‑sampling for high‑risk human papillomavirus as a follow‑up alternative after treatment of high‑grade cervical intraepithelial neoplasia

“…A recent investigation ( 26 ) comparing histologic findings and triple HPV results in women undergoing colposcopy revealed that urine-based HPV testing was somewhat less sensitive in identifying women with high-grade CIN, compared to VSS and provider-sampled HPV results, similarly to our study. Our samples were from the initial urine stream, thought to contain highest concentrations of diagnostically relevant components ( 27 ) and to be more accurate for detecting cervical HPV than mid-stream or end-stream samples ( 28 ).…”

Accuracy of human papillomavirus tests on self-collected urine versus clinician-collected samples for the detection of cervical precancer: a systematic review and meta-analysis

“…Thus, data from 30 combinations for urine and 25 combinations for clinician-collected samples were included in the meta-analysis, totaling to 11,159 and 10,774 women for each collection method, respectively. For the urinary HPV test studies, generally healthy women were enrolled in 4 combinations from 3 studies [ 15 29 31 ], whilst women who were referred to colposcopic clinics were enrolled in 26 combinations from 17 studies [ 7 12 13 14 16 17 18 19 20 21 22 23 24 25 26 28 30 ]. Women undergoing conization for CIN were enrolled in only one study [ 27 ].…”

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

“…This initial urine stream washes away, and hence collects, HPV-containing mucus and debris from exfoliated cells from the female genital organs lining the urethra opening. Indeed, recent clinical trials 4 collecting urine using a standardized sample collection protocol which includes use of FV urine and DNA preservative demonstrate higher hrHPV test agreement [15][16][17][18][19] and clinical sensitivity [9,12,[20][21][22] in self-collected urine versus cervical samples compared to trials where random or midstream urine was collected or not immediately preserved [23][24][25]. Although there are over 250 commercial HPV tests available on the global market to date, only few tests' performance are clinically validated for screening with an HPV assay according to either the Meijer guidelines (n=13), United States Food and Drug Administration (FDA) standards (n=2), or World Health Organization (WHO) prequalifications (n=3) [3].…”