Long-Term Follow-Up of HPV FOCAL Participants (HPV FOCAL)

Evaluation of CIN2+ Rates up to 120 Months After 48-Month Co-Testing (Long Term Follow up of HPV FOCAL Participants)

This FOCAL follow-up study aims to assess the long-term effectiveness and safety of primary HPV testing for cervical cancer screening. A cohort of participants from the original FOCAL study will be asked to see their health care provider to submit another cervical sample for cytology and HPV testing. This will permit evaluation of long term safety and effectiveness of primary HPV testing up to ten years after a participant's first screening in the FOCAL study and comparison of primary HPV testing to HPV and cytology co-testing.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Other: HPV and cytology co-testing (via Liquid based collection device)

Detailed Description

This study will evaluate the long-term effectiveness of primary HPV screening, with and without cytology co-testing at various time points and inform optimal algorithms for HPV-based cervical cancer screening. Specifically the project will compare rates of CIN2+ after primary HPV testing to rates of CIN2+ after baseline LBC testing followed by HPV and LBC "co-testing" at 48 months. We hypothesize that women who have a negative HPV result at baseline will have fewer CIN2+ lesions detected at 96 months or 120 months (or greater) after baseline than women who have a negative cytology (LBC) result at baseline, and who receive HPV/LBC co-testing at 48 months and at 96 months or greater after baseline.

Objectives

1. Determine detection rates of CIN2+ at approximately 48 months or 72 months (one sample only, depending on when women exited the trial) after the FOCAL 48 month exit HPV/LBC co-test screen in control arm women.
2. Compare CIN2+ rates from women in the intervention arm (HPV testing) at 48 month FOCAL HPV/LBC co-test screen, to CIN2+ rates of women in the control arm (LBC testing) receiving HPV/LBC co-testing up to 120 months or greater (if applicable). If CIN2+ outcomes are available beyond 120 months where available, this will be captured to ensure important endpoints are not missed because of a 120 month cut off. (For the remainder of this proposal, when indicating 120 months, this will include those with CIN2+ outcomes beyond 120 months).
3. Using passive follow-up by anonymized data linkage with the BC Cancer cervix screening registry, determine long term protection against CIN2+ up to 120 months after a negative HPV baseline result.

Women in the control arm (LBC testing at baseline) who completed the 48 month exit screen (HPV/LBC co-test) and who had no CIN2+ detected during the trial or at trial exit will be invited to participate. When women consented to participate in the HPV FOCAL trial, they were asked if they were interested in being contacted in the future for potential research studies related to cervical cancer. Women who indicated they would be interested and those who did not specifically state they did not want to be contacted, will be contacted.

An information letter will be sent to eligible participants with information describing the study. This information package will also include a link to a REDCap eConsent that has an eligibility survey and consent form. Interested women will be asked to complete this online eConsent form to give consent to participate. It is not possible to have face to face interactions with participants, given the nature of this trial, and electronic consent is the most feasible approach for this project. Electronic consent procedures will be followed per UBC guidelines and per US OHRP "Use of Electronic Consent" guidelines. https://www.fda.gov/media/116850/download.

After eligibility has been confirmed, women will be directed to their usual HCP for a cervical sample collection with Liquid based cytology, permitting for both HPV and cytology testing on the same sample.

All LBC samples will be sent to the PHL for HPV and cytology testing.

In order to compare the results of post- 48month trial exit follow-up for women in the FOCAL control arm (who had baseline LBC testing) to women in the FOCAL intervention arm (who had baseline HPV testing), a data linkage will be conducted between the FOCAL study database, the Cervix Screening Program Registry and the BC Cancer Registry, using BC Cancer Registry Data Linkage established procedures.

• Study Type: Observational
• Enrollment (Actual): 1710

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3N1
      • Women's Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Study population consists entirely of participants from a previous RCT.

Description

Inclusion Criteria:

• Previous HPV FOCAL study, control arm participants who completed 48 month FOCAL LBC/HPV co-testing with no CIN2+ detected at trial exit
• Resident of BC
• <69 years of age (upper age limit for routine screening per BC Cancer Cervix Screening program)
• No history of CIN2+ since FOCAL study exit or in the last 5 years
• Has not had a hysterectomy
• Has never had a diagnosis of invasive cervical cancer

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Women in the original HPV FOCAL control arm who completed the 48 month exit screen (HPV/LBC co-test) and who had no CIN2+ detected during the trial or at trial exit will be invited to submit another LBC sample for HPV and cytology co-testing.	Other: HPV and cytology co-testing (via Liquid based collection device); Liquid-based cytology co-testing is a procedure in which that a cervical sample is taken, and can be co-tested for HPV and standard cytology at the same time. It is collected in the same way that a traditional Pap is collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of CIN2+	Moderately abnormal cells are found on the surface of the cervix	120 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: National Cancer Institute (NCI); British Columbia Cancer Agency
• Investigators: Principal Investigator: Gina Ogilvie, MD, MSc FCFP DrPH, University of British Columbia; Study Director: Laurie Smith, MPH, BC Cancer

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): July 14, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: human papillomavirus; cytology; hpv testing; cervix screening
• 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: H19-01584; 5R01CA221918-02 (U.S. NIH Grant/Contract)

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