Self-sampling Among Long-term Non-attenders to Cervical Cancer Screening

Study Overview
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Brief Summary
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The trial will evaluate whether human papillomavirus (HPV) self-sampling may increase cervical cancer screening attendance among under-screened women in Norway, how different ways of offering self-sampling and follow-up may affect attendance, and whether self-sampling may reduce inequities in attendance.

Detailed Description
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A randomized control trial will be performed on the effect of vaginal HPV self-sampling on screening attendance, targeting women age 35-69 who have not attended screening for at least 10 years. The women will be randomly allocated to one of three interventions: (i) receive a reminder to be screened by a physician; (ii) receive a self-sampling kit; (iii) receive an offer to order a self-sampling kit. Comparisons of the screening attendance among the interventions will be made. To also address potential effects on inequities, the analyses will include comparisons by sociodemographic characteristics. The rates of cervical cancer/precancer among the interventions will also be compared. Further, to assess the feasibility of and the compliance to follow-up after a positive HPV test in this population, half of the HPV-positive women from each self-sampling arm will be referred to initial follow-up by their regular general practitioner (GP), while the other half will be referred to initial follow-up by a gynecologist. The project will be embedded in the national cervical cancer screening program, and will utilize the extensive nationwide registers describing performance and outcomes of screening collected by the Cancer Registry of Norway.

Official Title
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A Pragmatic Randomized Controlled Trial of Self-sampling Among Long-term Non-attenders to Cervical Cancer Screening

Conditions
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Cervical Cancer

Intervention / Treatment
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* Behavioral: Opt-in; Receive offer to order self-sampling kit
* Behavioral: Opt-out; Receive self-sampling kit unsolicited
* Behavioral: Control; Receive open reminder to be screened by physician


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women living in the regions Hordaland, Vest-Agder, Rogaland or Sør-Trøndelag, who have been eligible for screening in Norway, but who have not attended screening for at least 10 years (2009-2018) Exclusion Criteria: Women who have not been eligible for cervical cancer screening during the entire 10 year period (2009-2018)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 69 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Opt-in<br>Receive offer to order self-sampling kit | Behavioral: Opt-in; Receive offer to order self-sampling kit<br>* Women in the opt-in arm receive an offer to order a HPV self-sampling kit, in addition to information about the study. Women who order, receive a kit that includes a self-sampling brush (Evalyn, Rovers Medical Devices), with instructions for use and a pre-paid envelope for returning the brush for HPV testing. The women are also informed that they can attend ordinary screening, i.e. performed by a physician. Women who choose self-sampling and test positive for high-risk HPV will be 1:1 allocated to follow-up by their general practitioner or a gynecologist. Women who test negative for high-risk HPV return to the ordinary screening program<br>|
| Experimental: Opt-out<br>Receive self-sampling kit unsolicited | Behavioral: Opt-out; Receive self-sampling kit unsolicited<br>* Women in the opt-out arm receive the self-sampling kit directly, without having ordered it themselves. The kit has the same contents, and the follow-up is the same, as that described for the opt-in arm.<br>|
| Experimental: Control<br>Receive open reminder to be screened by physician | Behavioral: Control; Receive open reminder to be screened by physician<br>* Similar to the procedure of the national screening program, women in the control arm receive a reminder to be screened by their general practitioner, and continues in the ordinary screening program<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Screening attendance rate (%) | The primary outcome measure is the attendance rate to cervical cancer screening. Attendance is defined as returning a self-sampling test, or being screened by a physician during the 6 months following receipt of the invitation letter | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of high-risk HPV (%) | Self-samples as well as physician-taken samples will be tested for high-risk HPV with the Cobas 4800 HPV-DNA test at the national HPV reference laboratory | 6 months | 
| Prevalence of CIN2+ (proportion of cervical intraepithelial neoplasia grade 2 or worse) | Histologically confirmed CIN2+ diagnoses of all study participants who are eligible for follow-up will be retrieved from the cervical screening registry at the Cancer Registry of Norway | 6 months | 
| Compliance to clinical follow-up of a high-risk HPV positive screening test (%) | Attendance to follow-up among women with a positive screening test will be surveyed following notification of the positive test result. In addition to comparing arms, we will compare compliance of women in the self-sampling arms who are followed up by their regular GP vs. women who are followed up by a gynecologist | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mass screening, non-attendance, self-sampling, HPV