Cervical Cancer, Cervical Dysplasia, Genital Neoplasms, Female, HPV Infection, HPV-Related Cervical Carcinoma, HPV-Related Malignancy, Human Papilloma Virus, Neoplasms, Neoplasms by Site, Urogenital Neoplasms, Uterine Cervical Diseases, Uterine Cervical Neoplasm, Uterine Diseases, Uterine Neoplasms
Conditions
Keywords
Cancer Screening
Brief summary
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
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.
Interventions
OTHERUsual Care
Subjects will receive Kaiser Permanente Washington standard of care.
BEHAVIORALEducation
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.
BEHAVIORALDirect 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.
BEHAVIORALOpt-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.
Sponsors
National Cancer Institute (NCI)
University of Washington
University of Texas Southwestern Medical Center
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Investigator)
Intervention 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).
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Screening Completion by Outreach Approach and Prior Screening Behavior | Within 6 months of randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Screening Initiation by Outreach Approach and Prior Screening Behavior | Within 6 months of randomization | Screening Initiation defined as returning the home kit or receiving in clinic cervical cancer screening. |
| Time From Randomization to Screening Completion by Outreach Approach and Prior Screening Behavior | Within 6 months of randomization | 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. |
| Completion of Recommended Follow-up After a Positive Kit Result | Within 6 months of randomization | 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 |
| Incremental Cost-effectiveness Ratio by Outreach Approach and Prior Screening Behavior | Within 6 months of randomization | 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. |
| Qualitative Information From Focus Groups on Patient Preferences by Prior Screening Behavior | 6-12 months following study invitation | 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. |
| Health System Costs to Implementing Home Testing by Outreach Approach and Prior Screening Behavior | 3-5 years (projected) | 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. |
| Screening Method Choice | Within 6 months of randomization | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Usual Care: Subjects will receive Kaiser Permanente Washington standard of care. | 12,142 |
| Education 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. | 8,854 |
| Direct Mail 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. | 2,897 |
| Opt-in 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. | 7,462 |
| Total | 31,355 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Excluded from analysis, recent disenrollment from KPWA | 211 | 164 | 27 | 137 |
| Overall Study | Excluded from analysis, recent Papanicolaou test prior to randomization date | 356 | 261 | 50 | 210 |
Baseline characteristics
| Characteristic | Usual Care | Education | Direct Mail | Opt-in | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12142 Participants | 8854 Participants | 2897 Participants | 7462 Participants | 31355 Participants |
| Age, Continuous | 46.2 years STANDARD_DEVIATION 10.3 | 45.6 years STANDARD_DEVIATION 10.4 | 47.5 years STANDARD_DEVIATION 10 | 45.1 years STANDARD_DEVIATION 10.5 | 45.9 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 628 Participants | 502 Participants | 154 Participants | 421 Participants | 1705 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8047 Participants | 5278 Participants | 2307 Participants | 4446 Participants | 20078 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3467 Participants | 3074 Participants | 436 Participants | 2595 Participants | 9572 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 76 Participants | 50 Participants | 16 Participants | 41 Participants | 183 Participants |
| Race (NIH/OMB) Asian | 1298 Participants | 919 Participants | 326 Participants | 861 Participants | 3404 Participants |
| Race (NIH/OMB) Black or African American | 553 Participants | 411 Participants | 133 Participants | 315 Participants | 1412 Participants |
| Race (NIH/OMB) More than one race | 353 Participants | 261 Participants | 92 Participants | 208 Participants | 914 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 153 Participants | 120 Participants | 30 Participants | 69 Participants | 372 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2534 Participants | 2249 Participants | 398 Participants | 1792 Participants | 6973 Participants |
| Race (NIH/OMB) White | 7175 Participants | 4844 Participants | 1902 Participants | 4176 Participants | 18097 Participants |
| Region of Enrollment United States | 12142 participants | 8854 participants | 2897 participants | 7462 participants | 31355 participants |
| Sex: Female, Male Female | 12142 Participants | 8854 Participants | 2897 Participants | 7462 Participants | 31355 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12,142 | 0 / 8,854 | 0 / 2,897 | 0 / 7,462 |
| other Total, other adverse events | 0 / 12,142 | 0 / 8,854 | 4 / 2,897 | 3 / 7,462 |
| serious Total, serious adverse events | 0 / 12,142 | 0 / 8,854 | 0 / 2,897 | 0 / 7,462 |
Outcome results
Primary
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.
Time frame: Within 6 months of randomization
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Screening Completion by Outreach Approach and Prior Screening Behavior | Unknown | 2983 Participants |
| Usual Care | Screening Completion by Outreach Approach and Prior Screening Behavior | Screening-Adherent | 3671 Participants |
| Usual Care | Screening Completion by Outreach Approach and Prior Screening Behavior | Overdue | 5488 Participants |
| Education | Screening Completion by Outreach Approach and Prior Screening Behavior | Overdue | 1408 Participants |
| Education | Screening Completion by Outreach Approach and Prior Screening Behavior | Screening-Adherent | 3960 Participants |
| Education | Screening Completion by Outreach Approach and Prior Screening Behavior | Unknown | 3486 Participants |
| Direct Mail | Screening Completion by Outreach Approach and Prior Screening Behavior | Unknown | 0 Participants |
| Direct Mail | Screening Completion by Outreach Approach and Prior Screening Behavior | Screening-Adherent | 1482 Participants |
| Direct Mail | Screening Completion by Outreach Approach and Prior Screening Behavior | Overdue | 1415 Participants |
| Opt-in | Screening Completion by Outreach Approach and Prior Screening Behavior | Overdue | 0 Participants |
| Opt-in | Screening Completion by Outreach Approach and Prior Screening Behavior | Screening-Adherent | 3956 Participants |
| Opt-in | Screening Completion by Outreach Approach and Prior Screening Behavior | Unknown | 3506 Participants |
Comparison: Primary analysis stratified by screening history. These results are for Screening-Adherent (population):Direct-Mail versus Education analysis.p-value: 0.0595% CI: [1.23, 1.36]Poisson Regression with GEE
Comparison: Primary analysis stratified by screening history. These results are for Screening-Adherent (population):Opt-In versus Education analysis.p-value: 0.0595% CI: [1.02, 1.12]Poisson Regression with GEE
Comparison: Primary analysis stratified by screening history. These results are for Screening-Overdue (population):Direct-Mail versus Education analysis.p-value: 0.0595% CI: [1.68, 2.16]Poisson Regression with GEE
Comparison: Primary analysis stratified by screening history. These results are for Screening-Unknown (population):Opt-In versus Education analysis.p-value: 0.0595% CI: [1.03, 1.25]Poisson Regression with GEE
Secondary
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
Time frame: Within 6 months of randomization
Secondary
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.
Time frame: 3-5 years (projected)
Secondary
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.
Time frame: Within 6 months of randomization
Secondary
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.
Time frame: 6-12 months following study invitation
Secondary
Screening Initiation by Outreach Approach and Prior Screening Behavior
Screening Initiation defined as returning the home kit or receiving in clinic cervical cancer screening.
Time frame: Within 6 months of randomization
Secondary
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
Time frame: Within 6 months of randomization
Secondary
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.
Time frame: Within 6 months of randomization