Early effects of HPV vaccination on high-grade cervical intraepithelial neoplasia in Brazil: Evidence from outpatient data

Cervical cancer remains a leading cause of disease burden among women, despite being largely preventable. High-grade cervical intraepithelial neoplasia (CIN) is a key intermediate outcome for evaluating early population-level effects of HPV vaccination and is mainly managed in outpatient settings, which may provide a more timely signal than hospitalizations or cancer registry data. This study aimed to assess whether the introduction of quadrivalent HPV vaccination in Brazil in 2014 through its National Immunization Program was associated with changes in first outpatient consultations for high-grade CIN. We conducted a quasi-experimental interrupted time-series analysis using Brazil's Outpatient Information System, including females aged ≥15 y with first eligible high-grade CIN records identified by ICD-10 codes and relevant procedures. Descriptive trends were assessed from 2011 to 2023, and interrupted time-series models were restricted to 2011-2019. Age-specific consultation counts and rates were calculated, and segmented regression models were fitted using generalized linear models. Negative controls included consultations for non-HPV sexually transmitted infections (STIs) and trends among older age groups not directly targeted by vaccination. Among adolescents aged 15-19 y, high-grade CIN consultation rates increased from 5.5 per 100,000 women in 2011 to a peak of 7.1 in 2015, followed by a decline to 1.8 in 2023, falling below pre-vaccination levels. Older age groups did not show comparable declines, while non-HPV STI consultations increased steadily across all ages. These contrasting trends support a vaccine-related effect in adolescents and indicate that the observed decline is unlikely to reflect changes in healthcare-seeking behavior or reporting practices.