Validation of the clinical performance and reproducibility of the NeuMoDx HPV assay self-sample workflow

•Self-sampling is a key strategy for equitable access to cervical cancer screening.•HPV self-sample workflows need to be validated to assure safe use in screening.•NeuMoDx HPV self-sample workflow demonstrates high clinical accuracy for CIN2+/3+.•NeuMoDx HPV self-sample workflow is highly reproducible.•NeuMoDx HPV self-sample workflow can be considered validated for screening purposes. Human papillomavirus (HPV) testing on self-samples is a valid tool for cervical cancer screening. HPV self-sample workflows need to be clinically validated to ensure safe use in screening. This study evaluated the fully automated NeuMoDx HPV Assay self-sample workflow that is compiled of the NeuMoDx HPV assay and the NeuMoDx 96/288 Molecular Systems, for clinical performance and reproducibility on Evalyn Brush-collected self-samples. The clinical performance of the NeuMoDx HPV Assay self-sample workflow for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ was evaluated on 987 self-samples obtained from women attending national organized HPV-based cervical cancer screening by a noninferiority analysis relative to reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR. Intra- and inter-laboratory reproducibility of the NeuMoDx HPV Assay self-sample workflow using both NeuMoDx 96 and 288 Molecular Systems was assessed on 520 self-samples in three laboratories. The clinical sensitivity and specificity of the NeuMoDx HPV Assay self-sample workflow for the detection of CIN2+ and CIN3+ were found to be non-inferior to the reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR, with all p-values