OBJECTIVES: To identify areas with high rates of high-risk Papillomavirus (hrHPV) infection and associated contextual factors in the Centre Region of Portugal at the municipality level. STUDY DESIGN: We conducted an ecological study in 78 municipalities located in the Central Region of Portugal from March 2019 to December 2022. METHODS: We used data from the cervical cancer screening (CCS) program database after switching to primary HPV testing. Demographic, socio-economic, and healthcare availability variables were extracted from official sources (Statistics Portugal and Central Region Health Administration Information Systems). Spatial analysis and logistic generalised linear models were used to identify areas of high hrHPV infection and associated contextual factors. RESULTS: The overall hrHPV infection prevalence was 9.9%. We found three significant clusters, predominantly in municipalities near major urban centres. These clusters were characterised by higher population density, a greater proportion of younger women, higher median income per inhabitant, a larger proportion of residents with graduate degrees, and increased availability of healthcare units. CONCLUSIONS: This study has uncovered the geographical distribution of hrHPV infection at the municipal level and highlights the contextual factors associated with higher prevalence. Identifying demographics and socio-economic predictors of high hrHPV infection could support public health programs by targeting interventions to specific populations and contexts. This might open up new scenarios for improving prevention and control strategies, offering more intensive screening in areas with the most urgent needs.