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Introduction: To direct interventions, the Florida counties with the greatest risk of current and future human papillomavirus‒associated cancers were identified by estimating county-level (1) percentages of adolescents aged 13-17 years who initiated (≥1 dose) and were up to date (2-3 doses) for the human papillomavirus vaccine and (2) human papillomavirus‒associated cancer incidence rates., Methods: Records were obtained for human papillomavirus vaccinations from the Florida immunization registry (2006-2019), incident cancer cases from the Florida registry (2013-2017), and annual population counts from the Florida Department of Health (2006-2019). In 2020, annual county-level human papillomavirus vaccine initiation, human papillomavirus vaccine up-to-date, and age-adjusted human papillomavirus‒associated cancer incidence rates were estimated., Results: Among adolescents aged 13-17 years, average 2018-2019 county-specific human papillomavirus vaccine initiation ranged from 38% to 100% for females and from 34% to 96% for males. Up-to-date estimates ranged from 20% to 72% for females and from 24% to 77% for males. The majority (78%) of counties with initiation and up-to-date estimates within the lowest tercile were located in Northern Florida. County-specific 2013-2017 annualized, adjusted human papillomavirus‒associated cancer incidence rates ranged from 0 to 29.8 per 100,000 among females and from 5.4 to 24.1 per 100,000 among males. Counties within the highest tercile for human papillomavirus‒associated cancers were primarily (90% for females and 77% for males) located in Northern Florida., Conclusions: Human papillomavirus‒associated cancer risk varies widely across Florida counties, with particularly high risk within Northern Florida. Targeting interventions toward counties with low vaccination and high cancer rates may reduce human papillomavirus‒associated cancers., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)