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Background  New cervical cancer screening guidelines recommend primary human papillomavirus (HPV) testing for women age 30–65 years. Healthcare organizations are preparing to de-implement the previous recommended strategies of Pap testing or co-testing (Pap plus HPV test) and substitute primary HPV testing. However, there may be significant challenges to the replacement of this entrenched clinical practice, even with an evidence-based substitution. We sought to identify stakeholder-perceived barriers and facilitators to this substitution within a large healthcare system, Kaiser Permanente Southern California.    Methods  We conducted semi-structured qualitative interviews with clinician, administrative, and patient stakeholders regarding (a) acceptability and feasibility of the planned substitution; (b) perceptions of barriers and facilitators, with an emphasis on those related to the de-implementation/implementation cycle of substitution; and (c) perceived readiness to change. Our interview guide was informed by the Consolidated Framework for Implementation Research (CFIR). Using a team coding approach, we developed an initial coding structure refined during iterative analysis; the data were subsequently organized thematically into domains, key themes, and sub-themes using thematic analysis, followed by framework analysis informed by CFIR.    Results  We conducted 23 interviews: 5 patient and 18 clinical/administrative. Clinicians perceived that patients feel more tests equals better care, and clinicians and patients expressed fear of missed cancers (“…it’ll be more challenging convincing the patient that only one test is…good enough to detect cancer.”). Patients perceived practice changes resulting in “less care” are driven by the desire to cut costs .  In contrast, clinicians/administrators viewed changing from two tests to one as acceptable and a workflow efficiency (“…It’s very easy and half the work.”). Stakeholder - recommended strategies included focusing on the increased efficacy of primary HPV testing and developing clinician talking points incorporating national guidelines to assuage “cost-cutting” fears.    Conclusions  Substitution to replace an entrenched clinical practice is complex. Leveraging available facilitators is key to ease the process for clinical and administrative stakeholders—e.g., emphasizing the efficiency of going from two tests to one. Identifying and addressing clinician and patient fears regarding cost-cutting and perceived poorer quality of care is critical for substitution. Multicomponent and multilevel strategies for engagement and education will be required.    Trial registration  ClinicalTrials.gov, # NCT04371887Supplementary Information  The online version contains supplementary material available at 10.1186/s43058-021-00211-z.

implementation science communications

De-implementation and substitution of clinical care processes: stakeholder perspectives on the transition to primary human papillomavirus (HPV) testing for cervical cancer screening