Urinary and Vaginal HPV Testing in Cervical Cancer Screening

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Diagnostic Test: urine self-sampling group
* Diagnostic Test: clinician-collected cervical sample group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: urine self-sampling group|collection of urine and vaginal samples|
|Diagnostic Test: clinician-collected cervical sample group|A clinician takes a smear from cervix according to standard routine|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV DNA tests, self-collection, cervical cancer screening