High-Risk Human Papillomavirus Prevalence and Genotype Distribution in Two Opportunistic Cervical Screening Periods in Spain: A Tertiary Hospital-Based Study

High-risk human papillomavirus (HPV) infection is the main cause of cervical cancer and a central target of vaccination and screening programs. This study aimed to evaluate temporal changes in high-risk HPV prevalence and genotype distribution and their association with cytological and histological findings in an opportunistic screening population. Cervical cytology samples processed in 2013-2015 and 2022-2024 at a tertiary center in Spain were analyzed using the same high-risk HPV assay (n = 4724). Age-standardized prevalence and multivariable logistic regression models were applied, and birth cohort (≥ 1994 vs. < 1994) was used as an ecological proxy for vaccination exposure. After age standardization, high-risk HPV prevalence declined from 35.2% in 2013-2015 to 22.8% in 2022-2024, and screening in the later period was independently associated with lower odds of HPV infection (adjusted odds ratio 0.53). Most high-risk genotypes decreased over time, whereas HPV45 and HPV68 showed higher adjusted odds of detection. Coinfection prevalence declined. HPV positivity increased with cytological severity, and high-grade lesions clustered mainly around HPV16, HPV31, HPV52, HPV58 and HPV66. These findings highlight evolving patterns of high-risk HPV genotype distribution and support genotype-specific surveillance.