Objectives: To estimate the impact of differentiating between persistent and new HPV infections on the colposcopy referral rate in HPV-positive triage-negative women. Design: secondary analyses from a multicentric randomized clinical trial Setting: five Italian cervical cancer screening programs Population: 1,540 women enrolled in the NTCC2 trial, who were baseline HPV-DNA-positive and genotyped by the Onclarity HPV assay, without CIN2+ at baseline, and with a cervicovaginal sample collected at 1-year retesting. Methods: Comparing the genotyping results at baseline and 1-year retesting, we defined the outcomes as: persistent infections (at least one common genotype between baseline and 1-year retesting specimens) and new infections (positivity for different genotypes at retesting, with no baseline genotypes detected). Main Outcome Measures: proportions of persistent and new infections; reduction of colposcopy referral due to not referring new infections. Results: 613 women still HPV-DNA positive at 1-year retesting were genotyped and 556 were Onclarity-positive at both baseline and retesting: 488 (79.6%) had persistent infections, while 68 (11.1%) had new ones. Overall, 11 CIN3 were diagnosed at 1 year, all among women with persistent infections. If an alternative management strategy, rather than immediate colposcopy, was considered for women with new infections, and knowing that, in the Italian screening programs, 1-year retesting accounts for about 60% of colposcopies, the total colposcopy referral rate could be reduced by approximately 7%. Conclusions: The use of extended genotyping to differentiate new and persistent infections has the potential to reduce the colposcopy burden.