BackgroundHuman papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. In a large pilot implementation, we compared participation, referrals and detection of high-grade cervical intraepithelial neoplasia (CIN) in HPV- versus cytology-based cervical cancer screening.MethodsThe implementation was embedded into the routine screening program at Lillebaelt Hospital, Department of Pathology, Vejle, Denmark. Based on the area of residence, women aged 30–59 years were screened by either HPV testing (with HPV16/18 genotyping and cytology triage) or cytology (with HPV triage for minor abnormalities). Our analysis includes women invited or screened during May 2017–May 2018 (invited: n=35,081; screened: n=28,352) with 6 months of follow-up. Information on screening results and sociodemographic characteristics were obtained from registers. Using logistic regression, we estimated odds ratios (ORs) with 95% confidence intervals (CIs) of participation, referral and CIN3+-detection in HPV- versus cytology-based screening, adjusting for sociodemographic characteristics.ResultsParticipation was virtually identical in the HPV- and cytology group (58.4% vs 58.8%; ORadjusted=0.97, 95% CI, 0.93–1.01). Referral to colposcopy was more common in the HPV- than cytology group (3.8% vs 2.1%; ORadjusted=1.88, 95% CI, 1.63–2.17). More cases of CIN3+ were detected in the HPV- than cytology group (1.0% vs 0.7%, ORadjusted=1.47; 95% CI, 1.13–1.91).ConclusionParticipation did not differ between HPV- and cytology-based screening. HPV-based screening detected more cases of CIN3+, but in this initial screening round also led to more colposcopies than cytology-based screening.