Agreement and Diagnostic Performance of Urinary HPV Testing Versus Clinician-Collected Cervico-Vaginal Sampling: A Prospective Cross-Sectional Study in a Romanian Cohort.
Background: Cervical cancer screening uptake in Romania remains below 20%, with invasive sampling cited as a major participation barrier. Urinary HPV testing is a non-invasive alternative, but data from Eastern European populations are scarce and reporting stratified by histological grade is inconsistent. Objectives: To evaluate the agreement between paired urinary and clinician-collected cervico-vaginal HPV testing, and to assess the diagnostic performance of urinary HPV testing for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Methods: Prospective cross-sectional study in three outpatient obstetrics and gynecology clinics (May 2025-May 2026). A total of 230 women aged 25-70 years provided paired cervico-vaginal (PreservCyt®) and first-void urine (Colli-Pee®) specimens. To capture the full spectrum of disease probability, participants were recruited across three clinical scenarios: primary screening, cytology triage and HPV-positive triage. A multiplex RT-PCR assay targeted a total of 14 high-risk HPV genotypes, providing separate identification for HPV16 and HPV18, alongside a pooled detection for the remaining 12 high-risk strains. Colposcopy-guided cervical biopsy served as the reference standard. Results: Paired hrHPV testing achieved substantial agreement (κ = 0.696, 95% CI 0.604-0.788), with higher genotype-specific concordance for HPV16 (κ = 0.755) and HPV18 (κ = 0.789). Discordance was directionally asymmetric (30 cervical-positive/urine-negative versus 4 urine-positive/cervical-negative; McNemar p < 0.001). For biopsy-confirmed CIN2+ (59 of 230; 25.7%), urinary hrHPV showed a sensitivity of 86.4% (95% CI 75.5-93.0), specificity 56.7%, positive predictive value 40.8% and negative predictive value 92.4%, compared with 91.5%, 43.3%, 35.8% and 93.7% for cervico-vaginal testing. Urinary HPV positivity increased monotonically with histological severity (25.0% no-lesion, 69.0% CIN1, 86.4% CIN2+; linear-by-linear p < 0.001). Conclusions: Urinary HPV testing demonstrates substantial agreement with clinician-collected sampling, near-equivalent negative predictive value, and a robust dose-response with histological severity. It is a clinically credible non-invasive entry point for a triage cascade in settings such as Romania, where low participation rather than analytical performance is the principal screening barrier.
Authors
Nati Nati, Oancea Oancea, Mihu Mihu, Mihu Mihu, Ciortea Ciortea, Iuhas Iuhas, Bucuri Bucuri, Roman Roman, Ormindean Ormindean, Suciu Suciu, Chereches Chereches, Malutan Malutan
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