Impact of HPV vaccination in Spain: Reductions in vaccine-type genotypes, cytological abnormalities, and the influence of epidemiological factors

Data evaluating human papillomavirus (HPV) vaccine impact in Spain remain limited. We aimed to assess HPV and cytology findings among vaccinated and unvaccinated women as an early indicator of its effectiveness. During April 2024-January 2026, a total of 908 women participating in a population-based cervical cancer screening in three regions of Spain were recruited (58% vaccinated). Cervical samples and epidemiological and vaccination data were obtained. HPV was detected in 37% (337/908) and high-risk HPV in 24% (221/908). High-grade cytological lesions (1.2%, 11/907) were more frequent in unvaccinated women (2.4% vs 0.38%, p=0.011) and showed higher prevalence of HPV 16/18 (5.5% vs 0.76%; aOR: 4.9; 95% CI: 1.4–17) and HPV31 (3.4% vs 1.3%; aOR: 2.7; 95% CI: 1.0–6.9) compared with vaccinated women. HPV51 and HPV70 were more frequent among vaccinated women; however, both were associated with factors unrelated to vaccination. HPV51 was linked to a higher number of sexual partners (aOR: 2.6; 95% CI: 1.2–5.6), while HPV70 to smoking (aOR: 0.36; 95% CI: 0.13–0.99). Lower detection of HPV 16/18, HPV31 and high-grade lesions among vaccinated women supports vaccine effectiveness and cross-protection, highlighting the importance of continuous comprehensive surveillance of HPV genotype, including epidemiological and sexual behavioral factors.