Urinary and Vaginal HPV Testing in Cervical Cancer Screening

Urinary and Vaginal HPV Testing as a Novel Cervical Cancer Screening Tool: a Diagnostic Test Accuracy Study

Cervical cancer, caused by high-risk human papillomavirus (HPV) infection, poses a problem worldwide as it is the fourth most common female cancer. Fifty percent of all invasive cervical cancers occur among the 25% not attending cervical cancer screening. To reach these women, this project will contribute to the development of a novel and accurate urinary and vaginal screening tool, which allows women to collect the screening samples at home. This project tests the hypotheses: 1) urinary HPV testing is non-inferior to HPV testing on clinician-collected cervical samples for detection of high-grade cervical pre-cancer, 2) Vaginal HPV testing is non-inferior to HPV testing on clinician-collected cervical samples for detection of high-grade cervical pre-cancer and 3) DNA methylation testing is suitable as a colposcopy triage test among women with HPV-positive urine and/or vaginal samples to prevent unnecessary colposcopies and overtreatment of women without clinically meaningful HPV infections. If confirmed, urinary and vaginal HPV testing could revolutionize todays screening programs and keep Denmark at the forefront of cervical cancer prevention.

Study Overview

• Status: Not yet recruiting
• Conditions: Uterine Cervical Neoplasms
• Intervention / Treatment: Diagnostic test: urine self-sampling group; Diagnostic test: clinician-collected cervical sample group

Detailed Description

Paired urine, vaginal, and clinician-collected cervical samples will be obtained from approximately 330 women aged 23-64 years referred for colposcopy and cervical biopsies due to abnormal screening result or referred for cervical excision due to treatment of CIN2+. Upon informed consent, the women will collect a first-void urine sample and a vaginal self-sample. Before colposcopy or excision, a clinician will collect a cervical sample. Among women referred for colposcopy, four cervical punch biopsies will be taken. For women referred for excision, a cone biopsy will be taken using a loop electrosurgical excision procedure. Upon arrival in the laboratory, the paired urine, vaginal and cervical samples will be HPV tested using the Cobas 4800 HPV DNA assay. Histological results will served as reference and be grouped as ≤CIN1 (normal tissue, CIN1) versus CIN2+. The performance of the six individual methylation markers and combinations thereof will be evaluated using the histological results as reference.

The primary endpoint will be the relative sensitivity and specificity of HPV testing in first-void urine, vaginal self-sample versus clinician-collected cervical samples to detect CIN2+. Non-inferiority of HPV testing between sample types will be evaluated against a margin of 90% for sensitivity and 98% for specificity. The performance of each methylation marker will be illustrated by ROC curves and assessed by the area under the curve.

• Study Type: Observational
• Enrollment (Anticipated): 330

Contacts and Locations

• Study Contact: Name: mette tranberg, post doc; Phone Number: +45 7842 0264; Email: mettrani@rm.dk
• Study Contact Backup: Name: Berit Andersen, prof. MD; Phone Number: +45 7842 0171; Email: berand@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

women aged 23-64 years referred for colposcopy and cervical biopsies due to abnormal cervical cancer screening result or referred for cervical excision due to treatment of CIN2+

Description

Inclusion Criteria:

• Females
• Aged 23-64 years
• Referred for colposcopy and cervical biopsies or referred for cervical excision

Exclusion Criteria:

• younger than 23 years
• older than 64 years
• not provided informed conte

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relative sensitivity and specificity of urinary sampling	The primary endpoint will be the relative sensitivity and specificity of HPV testing in first-void urine versus clinician-collected cervical samples to detect CIN2+	at baseline
relative sensitivity and specificity of vaginal self-sampling	The primary endpoint will be the relative sensitivity and specificity of HPV testing in vaginal self-samples versus clinician-collected cervical samples to detect CIN2+	at baseline

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: University Clinic for Cancer Screening, Department of Public Health Programmes, Randers Regional Hospital, Denmark; Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium; Department of Gynecology, Randers Regional Hospital, Denmark; Departement of Pathology, Randers Regional Hospital , Denmark
• Investigators: Principal Investigator: Mette Tranberg, post doc, Randers Regional Hospital and Aarhus University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 18, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: HPV DNA tests, self-collection, cervical cancer 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: 2703

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