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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Uterine Cervical Neoplasm, Uterine Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Uterine Cervical Diseases, Uterine Diseases, Cervical Cancer, Cervical Dysplasia, Human Papilloma Virus, HPV-Related Cervical Carcinoma, HPV Infection, HPV-Related Malignancy

Intervention / Treatment
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* Other: Usual Care
* Behavioral: Education
* Behavioral: Direct Mail
* Behavioral: Opt-in


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The investigators will test interventions separately by prior cervical cancer screening behavior: Screening Adherent, Overdue, and Unknown history. Interventions will differ by screening behavior. Previously Adherent: Previously screened for cervical cancer with a known due date within three months Overdue: Never screened for cervical cancer; or HPV and Pap co-test >5.25 years ago [or Pap alone >3.25 years ago]; or no past Pap and continuously enrolled at Kaiser Permanente Washington for ≥3.25 years. Unknown Prior Screening Behavior: Enrolled at Kaiser Permanente Washington for ≥6 months and <3.25 years, with no recorded cervical cancer screening history. Cohort randomization allocation will be assigned as follows to intervention arms: Previously Adherent (Usual Care, Education, Opt-in, and Direct Mail); Overdue (Usual Care, Education, and Direct Mail); and Unknown (Usual Care, Education, and Opt-in).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care<br> | Other: Usual Care<br>* Subjects will receive Kaiser Permanente Washington standard of care.<br>|
| Active Comparator: Education<br> | Behavioral: Education<br>* 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.<br>|
| Active Comparator: Direct Mail<br> | Behavioral: Direct Mail<br>* 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.<br>|
| Active Comparator: Opt-in<br> | Behavioral: Opt-in<br>* 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.<br>|

What is the study measuring?
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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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Screening