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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5669
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Pb 5313 Majorstuen
    • Oslo, Pb 5313 Majorstuen, Norway, 0304
      • Cancer Registry of Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sociodemographic characteristics (%)	We will compare the distribution of sociodemographic characteristics (income, education, immigration status, age etc.) by intervention and attendance status	Up-to-date sociodemographic data retrieved from national registries in 2019

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo; Albert Einstein College of Medicine; University of Bergen; University Hospital, Akershus; Cancer Registry of Norway
• Investigators: Study Director: Giske Ursin, MD, Prof, Oslo University Hospital

Publications and helpful links

General Publications

• Aasbo G, Trope A, Nygard M, Christiansen IK, Baasland I, Iversen GA, Munk AC, Christiansen MH, Presthus GK, Undem K, Bjorge T, Castle PE, Hansen BT. HPV self-sampling among long-term non-attenders to cervical cancer screening in Norway: a pragmatic randomised controlled trial. Br J Cancer. 2022 Nov;127(10):1816-1826. doi: 10.1038/s41416-022-01954-9. Epub 2022 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: HPV; mass screening; self-sampling; non-attendance
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: 18/14056; 182687 (Other Identifier: Cancer Society of Norway (Funder))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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