Self-Testing Options in the Era of Primary HPV Screening for Cervical Cancer Trial (STEP)

Self-Testing Options in the Era of Primary HPV Screening for Cervical Cancer: the STEP Trial

The Self-Testing options in the Era of Primary HPV screening for cervical cancer (STEP) trial will evaluate effectiveness of home-based HPV kits for improving cervical cancer screening uptake and its cost-effectiveness. The investigators will compare cervical cancer screening uptake within six months among women randomized to different outreach approaches based on prior screening behavior: A) Adherent and coming due: direct mail HPV kit vs. opt-in HPV kit vs. education; B) Overdue: direct mail HPV kit vs. education; C) Unknown: opt-in HPV kit vs. education.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Cervical Cancer; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; HPV-Related Malignancy; HPV Infection; HPV-Related Cervical Carcinoma; Human Papilloma Virus; Uterine Cervical Neoplasm; Cervical Dysplasia
• Intervention / Treatment: Other: Usual Care; Behavioral: Education; Behavioral: Direct Mail; Behavioral: Opt-in

Detailed Description

The scientific objective of the proposed research is to study whether an in-home programmatic HPV screening outreach strategy improves cervical cancer screening initiation and uptake. Identifying new, patient-centered options that motivate continued screening initiation and uptake is essential now and in the future.

In August 2018, the US Preventive Services Task Force released updated cervical cancer screening guidelines that include human papillomavirus (HPV) testing alone (ie, primary HPV screening) as a newly recommended strategy for women aged 30-65 years. With primary HPV screening, home-based screening is an emerging option, because HPV tests (unlike Pap tests) can be performed on clinician- or self-collected samples. Self-collected samples are as sensitive as clinician-collected samples in detecting HPV and mailing HPV self-sampling kits increases screening participation. As US healthcare systems prepare to implement primary HPV screening, they will need to consider a variety of strategies. To date, HPV self-sampling randomized clinical trials have included only overdue women; no study has evaluated uptake and acceptance of HPV self-sampling kits as an alternative to in-clinic screening in a screening-adherent population.

Based on our Home-based Options to Make cervical cancer screening Easy (HOME) trial (ClinicalTrials.gov, NCT02005510), most women will test negative (88%) and can continue routine screening; 11% will require in-clinic follow-up: 3% directly to colposcopy (HPV-16/18+ results) and 8% to Pap because of "HPV+ other" results or an unsatisfactory result (<1%). For home-based HPV screening strategies to be successful, ensuring high follow-up compliance in the minority of women who test positive is critical.

• Study Type: Interventional
• Enrollment (Actual): 32771
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98101
      • Kaiser Permanente Washington Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Currently enrolled at Kaiser Permanente Washington
• Female sex
• 30 years to 64 years of age
• An intact cervix
• Has a primary care provider at Kaiser Permanente Washington

Exclusion Criteria:

• Anyone flagged by the delivery system as being on a non-routine screening schedule
• Previously randomized to the intervention arm of the HOME trial or invited to the PATH study (Participants from the PATH study and individuals randomized to the intervention arm in the HOME Study are excluded from STEP because their prior inclusion in a STEP-related research study could influence their screening uptake and affect the outcome of this trial.)
• On "do not contact list" for research studies
• Currently pregnant or had a pregnancy-related procedure within prior 3 months
• Language interpreter needed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care	Other: Usual Care; Subjects will receive Kaiser Permanente Washington standard of care.
Active Comparator: Education	Behavioral: Education; Participants will receive an Educational Brochure describing why screening for cervical cancer is important, information about HPV and its role in cervical cancer, and different strategies for cervical cancer screening.
Active Comparator: Direct Mail	Behavioral: Direct Mail; Participants will receive an Educational Brochure describing why screening for cervical cancer is important, information about HPV and its role in cervical cancer, and different strategies for cervical cancer screening. Participants will also receive an insert describing the home-based cervical cancer screening option and that a kit will be sent within 1 week. An HPV self-collection kit with instructions and a pre-paid return envelope (to Kaiser Permanente Washington's laboratory) will be sent to individuals with instructions on how to complete the kit.
Active Comparator: Opt-in	Behavioral: Opt-in; Participants will receive an Educational Brochure describing why screening for cervical cancer is important, information about HPV and its role in cervical cancer, and different strategies for cervical cancer screening. Participants will receive an Opt-in Insert describing the home-based cervical cancer screening option and how to request a kit. Individuals can request a kit by phone or through a webpage. Individuals who request a kit will receive the HPV self-collection kit with instructions and a pre-paid return envelope (to Kaiser Permanente Washington's laboratory) will be sent to individuals with instructions on how to complete the kit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening Completion by Outreach Approach and Prior Screening Behavior	Rate of completing cervical cancer screening completion by outreach approach and prior screening behavior. Screening completion defined by returning the home kit and attending the recommended in clinic follow-up (if applicable); or receiving in clinic screening.	Within 6 months of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental Cost-effectiveness Ratio by Outreach Approach and Prior Screening Behavior	Incremental cost-effectiveness ratio, which will be defined for each outreach approach within each screening behavior subgroup. Also, comparisons across screening behavior subgroups of usual care plus education to usual care.	Within 6 months of randomization
Time From Randomization to Screening Completion by Outreach Approach and Prior Screening Behavior	Time from randomization to screening completion by outreach approach and prior screening behavior. Screening completion defined by returning the home kit and attending the recommended in clinic follow-up (if applicable); or receiving in clinic screening.	Within 6 months of randomization
Screening Method Choice	Proportion of intervention group women who do not screen, return the home kit or receive in-clinic screening by outreach approach and prior screening behavior. Screening uptake outcome (no screen, home kit, or in-clinic) by outreach approach and by prior screening behavior	Within 6 months of randomization
Qualitative Information From Focus Groups on Patient Preferences by Prior Screening Behavior	Through focus groups, the investigators will explore patient preference for, and satisfaction with, home HPV screening and barriers to follow-up of abnormal screening results.	6-12 months following study invitation
Health System Costs to Implementing Home Testing by Outreach Approach and Prior Screening Behavior	Economic assessment of system-level financial consequences of adopting home-based HPV screening for cervical cancer. These analyses will evaluate the needed time to follow-up for the next cervical cancer screening to reduce gaps in cervical cancer screening HEDIS metrics, which also addresses program affordability.	3-5 years (projected)
Screening Initiation by Outreach Approach and Prior Screening Behavior	Screening Initiation defined as returning the home kit or receiving in clinic cervical cancer screening.	Within 6 months of randomization
Completion of Recommended Follow-up After a Positive Kit Result	Proportion of intervention group women who complete recommended follow-up after a positive kit result by outreach approach and prior screening behavior. Per current guidelines, in-clinic Pap after other-HR HPV positive; or colposcopy after HPV 16/18+ HPV self-collection	Within 6 months of randomization

Collaborators and Investigators

• Sponsor: Kaiser Permanente
• Collaborators: National Cancer Institute (NCI); University of Washington; University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Beverly B Green, MD, MPH, Kaiser Permanente; Principal Investigator: Rachel L Winer, PhD, MPH, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): July 29, 2023

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cancer Screening
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Precancerous Conditions; Neoplasms, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Uterine Cervical Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Uterine Cervical Dysplasia; Neoplasms by Site; Urogenital Neoplasms; Papillomavirus Infections; Uterine Neoplasms; Papilloma; Uterine Cervical Diseases
• Other Study ID Numbers: 00002344; R01CA240375 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Resources developed during the study will be made available in accordance with the NIH Data Sharing Policy to researchers in both the private and public sector free or for a nominal charge and with minimal restriction. Deidentified data will be made available to qualified investigators within 6 months of acceptance of the manuscript describing major outcomes. Requestors will be required to obtain IRB approval and sign a data use agreement before data will be released. The data use agreement must include the following commitments: a commitment to using the data for research purposes only and not to identify any individual participants or to disclose Kaiser Permanente proprietary information; a commitment to securing the data using appropriate computer technology; a commitment to destroying or returning the data after analyses are completed; and a commitment to meet any additional requirements that might be stipulated by Kaiser Permanente's Human Subjects Review Committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No