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In Italy, the first women invited for HPV vaccination at 15-16 years reached the age for cervical screening (25 years) in 2018. The real-world vaccination impact was evaluated. Women born in 1993-1996 invited for organised cervical screening in three Italian areas in 2018-2022 were eligible. After informed consent, they were tested for high-risk HPV and genotyped. Positives, triaged by cytology, were immediately referred to colposcopy if ASCUS+ (irrespective of genotyping); otherwise, recalled for cytology after 3 years. We estimated the relative (vaccinated with ≥ 2 doses vs. unvaccinated women) infection prevalence of three groups of genotypes: HPV16/18, HPV31/33/45 and HPV 35, 39, 51, 52, 56, 58, 59, 66, 68 ('non-vaccine preventable') and the relative positive predictive value (PPV) for histology-based CIN2+ detected at immediate colposcopy. Of 14,346 enrolled women, 34% had no vaccination, 66% ≥ 2 doses. The relative infection prevalence was 0.05 (0.03-0.10) for HPV16/18 without non-vaccine genotypes, 1.36 (1.23-1.50) for non-vaccine genotypes without HPV16/18 infections and 0.06 (0.03-0.12) for co-infections by both groups. The relative PPV for CIN2+ was very high (4.09; 1.40-12.01) in vaccinated women co-infected by HPV16/18 and non-vaccine types (4/9 vs. 7/84 cases) but reduced to zero in case of stand-alone HPV16/18 infections (0/12 vs. 15/117 cases). The CIN2+ relative detection in women infected only by non-vaccine types was 1.57 (0.87-2.82). The increase in infections and high-grade CIN from the pool of all non-vaccine genotypes requires further research (including pooling of data) to be confirmed with longer follow-up and on a larger study population.