HPV-based cervical screening: Rationale, expectations and future perspectives of the new Dutch screening programme.

Based on scientific data showing that HPV testing provides better protection against cervical precancer and cancer than cytology, in 2011 the Dutch Health Council advised the Minister of Welfare, Health and Sports to replace cytology by HPV testing in the Dutch population-based screening programme. After a successful evaluation of the feasibility of HPV-based screening in 2014, primary HPV testing for cervical screening was implemented in 2017. The Netherlands has been one of the first countries worldwide to implement nationwide HPV-based screening and its experience with the new programme is therefore followed with great interest. In this manuscript, we present an overview of the studies that were instrumental in the choice of HPV assay and triage strategy, the adjustment of screening starting and exit ages and intervals, and the implementation of HPV self-sampling. Finally, we review the cost-effectiveness of the proposed new screening algorithm and we explore future perspectives. The rationale behind the new Dutch HPV-based screening programme, which is based on risk management, could serve as a guidance to other countries that are planning to implement HPV-based screening in the near future.

Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.

Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of 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 with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.