ABSTRACT/SUMMARY Cervical cancer, entirely preventable, remains the 4th most common cause of cancer incidence and mortality in women, with over 12 million new cases predicted in the next 50 years without sustained scale-up of HPV vaccination and cervical screening. More than 80% of the disease burden occurs in low- and middle-income countries (LMICs), reflecting inequitable availability and adoption of effective preventive strategies. Unfortunately, sustainable implementation of cervical screening and management for cervical cancer prevention has been elusive in LMICs, reflecting challenges of implementing complex health interventions in complex adaptive health systems. In the parent study, using participatory systems thinking as our `grand theory', we integrated various implementation science frameworks into the Integrative Systems Praxis for Implementation Research (INSPIRE) to guide multilevel stakeholders through four phases of an iterative cycle of implementation activities, enabling stakeholder-engaged adaptation of complex health technologies to local health system contexts. In Aim 1 of the continuation of this project, we will conduct a realist evaluation of stakeholders involved in the INSPIRE research, to gain an understanding of the mechanisms through which the INSPIRE activities led to successful adoption and rapid scale-up of HPV-based testing in a large health network in the Peruvian Amazon. In Aim 2 we propose to translate the INSPIRE research methodology into a generalizable implementation strategy (Aim 2) – “Adaptation, Scale-Up, Sustainability: Implementation by Systems Thinking” (ASSIST) - and develop an implementation toolkit to enable stakeholder-engaged implementation planning and context adaptation. In Aim 3, we will leverage the planned scale-up of HPV implementation plans from the Peruvian Ministry of Health to test the ASSIST implementation strategy for impact on screening coverage and management using an interrupted time series design, using the extended RE-AIM evaluation framework. In parallel, we will conduct a qualitative comparative case study to enable understanding of context-dependent mediators and modifiers to the success of the ASSIST implementation strategy (Aim 3). The realist evaluations are designed to examine `what works for whom, in what circumstances, in what respects, and how' vs assuming that one size fits all. Ultimately, meeting our proposal aims will advance public health, by providing a broadly generalizable process and toolkit for context-adaption of HPV-based screening and management that can be used in LMICs, and implementation science, by helping to reduce the evidence gap in implementation science for approaching scale-up and sustainability of complex health interventions in diverse contexts.

PROJECT NARRATIVE Reducing the global disparities in cervical cancer – which is an entirely preventable disease – requires scale- up of available preventive interventions such as HPV vaccination and screening. Biomedical research has successfully developed technologies required to meet this demand; now we must complement this success with development of processes and tools to help countries adopt and integrate these prevention strategies into their routine public health services. Our project builds on a successful application of stakeholder-engaged systems thinking by developing the ASSIST (Adaptation, ScaleUp, Sustainability: Implementation by Systems Thinking) implementation strategy and toolkit, designed to enable countries to adapt and plan for HPV-based screening according to their own context, resources, preferences, and values.