The introduction of self-sampling in cervical cancer screening has raised the importance of HPV testvalidation on self-collected samples. This study aimed to evaluate the clinical performance of the OncoPredict HPV Screening (SCR) assay on self-collected vaginal and first-void urine (FVU) as part of the VALHUDES framework. Vaginal (FLOQSwabs) and FVU (Colli-Pee) samples were self-collected by 500 women referred to colposcopy, followed by a clinician-collected cervical sample prior to colposcopy, which were all tested using OncoPredict HPV SCR. OncoPredict HPV SCR demonstrated similar relative clinical sensitivity to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN2) in urine (ratio: 0.95 [95%CI 0.88-1.02]) and vaginal self-samples (ratio: 0.96 [95%CI 0.90-1.02]) compared to cervical samples. The clinical specificity was lower in vaginal but not in urine samples compared to cervical which improved following cut-off optimization. A higher cellularity was found in vaginal as compared to cervical and FVU samples. Moderate to excellent agreement in HPV detection in self-collected samples and cervical scrapes was demonstrated (Kappa values: 0.53 to 1.00). OncoPredict HPV SCR assay demonstrated similar accuracy on self-collected vaginal and FVU samples compared to cervical samples, although cut-off adjustment improved clinical specificity when applied to vaginal samples.