Mailed self-sample HPV testing kits to improve cervical cancer screening in a safety net health system: protocol for a hybrid effectiveness-implementation randomized controlled trial
Authors: Montealegre Jane R. , Anderson Matthew L. , Hilsenbeck Susan G. , Chiao Elizabeth Y. , Cantor Scott B. , Parker Susan L. , Daheri Maria , Bulsara Shaun , Escobar Betsy , Deshmukh Ashish A. , Jibaja-Weiss Maria L. , Zare Mohammed , Scheurer Michael E. 
Published: October 2020

Abstract
Background
Almost 20% of U.S. women remain at risk for cervical cancer due to their inability or unwillingness to participate in periodic clinic-based screening. Self-sampling has been shown to be an effective strategy for screening women for high-risk human papillomavirus (HR-HPV) infection in specific contexts. However, its effectiveness among medically underserved women in safety net health systems has not been evaluated. Furthermore, it is also unclear whether implementation strategies such as patient navigation can be used to improve the success of self-sample screening programs by addressing patient-level barriers to participation.

Methods/design
The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) trial is a hybrid type 2 effectiveness-implementation pragmatic randomized controlled trial of mailed self-sample HPV testing. The aim is to assess the effectiveness of mailed self-sample HPV testing kits to improve cervical cancer screening participation among patients in a safety net health system who are overdue for clinic-based screening, while simultaneously assessing patient navigation as an implementation strategy. Its setting is a large, urban safety net health system that serves a predominantly racial/ethnic minority patient population. The trial targets recruitment of 2268 participants randomized to telephone recall (enhanced usual care, n = 756), telephone recall with mailed self-sample HPV testing kit (intervention, n = 756), or telephone recall with mailed self-sample HPV testing kit and patient navigation (intervention + implementation strategy, n = 756). The primary effectiveness outcome is completion of primary screening, defined as completion and return of mailed self-sample kit or completion of a clinic-based Pap test. Secondary effectiveness outcomes are predictors of screening and attendance for clinical follow-up among women with a positive screening test. Implementation outcomes are reach, acceptability, fidelity, adaptations, and cost-effectiveness.

Discussion
Hybrid designs are needed to evaluate the clinical effectiveness of self-sample HPV testing in specific populations and settings, while incorporating and evaluating methods to optimize its real-world implementation. The current manuscript describes the rationale and design of a hybrid type 2 trial of self-sample HPV testing in a safety net health system. Trial findings are expected to provide meaningful data to inform screening strategies to ultimately realize the global goal of eliminating cervical cancer.

Trial registration
ClinicalTrials.gov NCT03898167. Registered on 01 April 2019.

Trial status
Study start data: February 13, 2020. Recruitment status: Enrolling by invitation. Estimated primary completion date: February 15, 2023. Estimated study completion date: May 31, 2024. Protocol version 1.6 (February 25, 2020).