Pooled performance of urinary human papillomavirus (HPV) testing for the presence of cervical HPV

Abstract Background Human papillomavirus (HPV) testing is the preferred method for cervical cancer screening. Noninvasive urinary HPV testing offers an attractive alternative to improve screening coverage among underscreened populations. However, few studies have assessed its performance in detecting cervical HPV via systematic review and meta‐analysis. Methods This study systematically searched PubMed, Embase, Web of Science Core Collection, and the Cochrane Library from inception until September 2023. The aim was to assess the performance of urinary HPV testing for detecting cervical HPV against two distinct reference standards: cervical HPV infection and histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+). The study also pooled results of vaginal self‐sampling and participants' attitudes toward urine sampling. This study was registered in PROSPERO (CRD42023462218). Results A total of 2292 records were initially retrieved, and four previous reviews were examined. The meta‐analysis was conducted in two primary parts on the basis of the reference standard. First, with cervical HPV infection as the reference standard, the analysis included 65 studies (17,766 individuals). Compared to cervical samples, urine samples had a lower detection rate for high‐risk HPV (46% vs. 53%; p = .110), with a pooled sensitivity of 76% (95% CI, 72%–80%) and specificity of 90% (95% CI, 87%–92%). Second, with CIN2+ as the reference standard, the analysis included 31 studies (15,054 individuals). In a direct comparison with paired data from 28 of these studies, urine samples demonstrated lower sensitivity than cervical samples (79% [95% CI, 72%–84%] vs. 93% [95% CI, 89%–96%]) but slightly higher specificity (58% [95% CI, 50%–65%] vs. 50% [95% CI, 42%–58%]). Additionally, with CIN2+ as the reference standard, this analysis of 21 studies (8974 individuals) showed that vaginal self‐samples had higher sensitivity (89% vs. 79%) but lower specificity (43% vs. 49%) compared to urine samples. Similar results were observed for CIN3+. Questionnaires or interviews conducted in 13 studies with 2426 participants revealed a greater preference for urine sampling. Conclusions Urinary HPV testing exhibits lower sensitivity than both cervical professional sampling and vaginal self‐sampling. Although its noninvasive nature supports its potential utility as a complementary strategy in resource‐limited or culturally conservative populations, it is not currently suitable for general population screening where standard methods are available because of its suboptimal performance and lack of standardized protocols for sampling and testing. Furthermore, standardization of sampling and testing protocols is required before routine implementation.