Human papillomavirus (HPV) testing is being increasingly incorporated into cervical cancer screening. VALGENT (VALidation of HPV GENotyping Tests) is a framework designed to evaluate the clinical performance of various HPV tests relative to the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay within the VALGENT-3 panel, and to compare its performance to the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in the routine cervical cancer screening, enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep aliquots and HPV testing was performed using the HPV-Risk assay, blinded to the clinical data. HPV prevalence was analysed and clinical performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) was assessed relative to the performance of the HC2. The sensitivity of the HPV-Risk assay for detection of CIN3+ was similar to that of the HC2 (relative sensitivity: 1.00; 95%CI: 0.95-1.05; p=1.000) with significantly higher specificity (relative specificity: 1.02; 95%CI: 1.01-1.04; p<0.001). For CIN2+, similar results were obtained with relative sensitivity of 0.98; 95%CI: 0.93-1.02 and relative specificity of 1.02; 95%CI: 1.01-1.03. The performance of the HPV-Risk assay for CIN3+ and CIN2+ was non-inferior compared to the HC2, with all p-values ≤0.006. In conclusion, the HPV-Risk assay demonstrated non-inferiority to the clinically validated HC2 through the VALGENT-3 panel for test validation and comparison.