Translating Molecular Diagnostics for Cervical Cancer Prevention into Practice

摘要/总结 宫颈癌是完全可以预防的，仍然是癌症发病率和死亡率的第四大常见原因， 女性，在未来50年内，如果没有HPV的持续扩大，预计将有超过1200万新病例 疫苗注射及子宫颈普查。80%以上的疾病负担发生在低收入和中等收入人群中， 这反映出有效预防战略的可获得性和采用情况不公平。 不幸的是，可持续地实施宫颈筛查和宫颈癌管理 预防在中低收入国家一直难以实现，这反映了在低收入国家实施复杂的卫生干预措施的挑战。 复杂的适应性卫生系统。在家长研究中，使用参与式系统思维作为我们的“大 理论”，我们将各种实施科学框架集成到集成系统实践中， 实施研究（INSPIRE），指导多层面利益攸关方完成迭代周期的四个阶段 实施活动的执行，使参与者能够参与将复杂的卫生技术应用于当地 卫生系统背景。在本项目的目标1中，我们将对以下方面进行现实主义的评估： 参与INSPIRE研究的利益攸关方，以了解 INSPIRE的活动导致在大型卫生机构中成功采用并迅速扩大了基于HPV的检测， 秘鲁亚马逊的网络。在目标2中，我们建议将INSPIRE研究方法转化为 可推广的执行战略（目标2）-“适应、扩大、可持续： 系统思维”（ASSIST）-并开发一个实施工具包， 实施规划和环境适应。在目标3中，我们将利用计划中的HPV规模扩大 执行计划，以测试ASSIST执行战略， 影响筛查覆盖率和管理使用中断的时间序列设计，使用扩展 RE-AIM评估框架。同时，我们将进行定性比较案例研究， 理解环境依赖的中介和修饰符，以成功实施ASSIST 战略（目标3）。现实主义的评价旨在审查“什么对谁有效，在什么方面有效 在什么情况下，在什么方面，以及如何与假设一个尺寸适合所有。最终，满足我们的提议 aims将通过提供一个可广泛推广的过程和适应环境的工具包来促进公共卫生 基于HPV的筛查和管理，可用于中低收入国家，以及实施科学， 减少实施科学方面的证据差距，以实现综合方案的扩大和可持续性， 不同背景下的卫生干预措施。

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.