•Self-collection is comparable to current practice for detecting cervical lesions.•Collection devices may have impact on disease detection and on acceptability.•Delays in specimen preparation can notably affect the performance of self-collection.•Only validated procedure should be used and any delays should be minimized. Comparative data on different self-collection methods is limited. To assess the impact of hrHPV testing of two self-collection devices for detection of cervical carcinoma and high-grade lesions. Three hundred ten patients collected two cervicovaginal specimens using a brush (Evalyn®Brush) and a swab (FLOQSwabs™), and filled a questionnaire at home. Then, a physician at the clinic took a cervical specimen into PreservCyt® buffer for hrHPV testing and cytology. All specimens were tested using Anyplex™ II HPV28, Cobas® 4800 HPV Test and Xpert®HPV. Performance comparison included 45 cervical carcinomas and 187 patients with premalignant lesions. Compared to the physician-specimen, hrHPV testing of Evalyn®Brush showed non-inferior sensitivity for CIN3+ (relative sensitivity of Anyplex™ 0.99; Cobas® 0.96; Xpert®HPV 0.97) while hrHPV testing of FLOQSwabs™ showed inferior sensitivity (relative sensitivity of Anyplex™ 0.91; Cobas® 0.92; Xpert®HPV 0.93). Similar results were observed for invasive carcinomas albeit that FLOQSwabs™ was statistically non-inferior to the physician-specimen. Self-collection by either Evalyn®Brush or FLOQSwabs™ was more sensitive for CIN3+ than LSIL or worse cytology. Significant decrease in sensitivity for CIN3+ were observed for FLOQSwabs™ when specimens were preprocessed for hrHPV testing after 28 days. Both devices were well accepted, but patients considered Evalyn®Brush easier and more comfortable than FLOQSwabs™. Self-collection is comparable to current screening practice for detecting cervical carcinoma and CIN3+ but device and specimen processing effects exist. Only validated procedure including collection device, hrHPV assay and specimen preparation should be used.