ABSTRACT HPV vaccination rates remain below target levels among adolescents in the United States, which is particularly concerning in safety-net populations with persistent disparities in HPV-associated cancer burden. There are numerous evidence-based strategies (EBS) designed to encourage HPV vaccination, but few programs are routinely used, much less sustained when research studies come to an end. The major research challenge we now face is not the lack of scientific knowledge about what works, but about how to integrate and sustain effective EBS for HPV vaccination within dynamic, real-world settings. Significant disruptions due to the COVID-19 pandemic further support the need to understand implementation context and processes for long- term sustainability and equity requirements of EBS for HPV vaccination in clinics serving safety-net populations (underinsured, low-income, marginalized communities). The R37 Parent Award consists of a four-year sequential mixed-methods study that identifies multilevel, community and clinic factors associated with implementation EBS for HPV vaccination within a multi-site Federally Qualified Health Care (FQHC) system. Guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework and Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) process, our multidisciplinary team will evaluate longer-term sustainability, maintenance and equity requirements for use of EBS for HPV vaccination and identify factors that impact broader system-level adoption in this R37 Merit Extension Award. We also explore factors required for scaling-out and optimization for other settings and contexts. Specific aims include: Aim 1: Assess longer-term sustainability, maintenance and equity of HPV Vaccine EBS in demonstration clinics; and Aim 2: Identify factors and core strategies needed for broader FQHC system-wide adoption (scale-up) of EBS and inform requirements for spread to other safety-net settings (scale-out). There is a dearth of data on sustainability, adaptation, and scale-up/out within implementation science as it relates to integrating EBS for HPV vaccination in safety-net settings, as most intervention and hybrid trials have limited timeframes to rigorously examine these longer-term outcomes. This R37 MERIT Extension request will leverage two additional years of funding to carry out a logical extension of the four-year funded parent award to fill a critical research gap in longer-term sustainability and equity in EBS for HPV vaccination in safety-net settings. Data obtained will also inform a larger pragmatic trial to advance the science in adaptation and fit of EBS in diverse contexts and settings in future research.