Validation of Human Papillomavirus Assays and Collection Devices for Self-samples and Urine Samples

Study Overview
=================
Brief Summary
-----------------
The VALHUDES study is a Diagnostic Test Accuracy study that aims to document the clinical accuracy of hrHPV testing on urine samples, collected under standardised and optimised conditions, and on two types of vaginal self-samples and compare results with those from matching samples taken by a clinician.

Detailed Description
-----------------
The samples are collected from patients referred to colposcopy because of prior cervical abnormalities. The patient takes at home two urine samples with the Colli-Pee device (a device that allows to collect first-void urine), the day before the visit to the colposcopy centre. At the colposcopy centre, two vaginal self-samples are taken by the patient herself: one with a cotton swab and a second with a plastic brush. Finally, the gynecologist takes a cervical Pap smear with a Cervex-Brush Combi. A real-time PCR test will be used to detect DNA of high-risk HPV types. It is possible that in the future also other tests will be validated on these samples. The colposcopy and histological findings will be used as the gold standard. The main purpose of the study is to assess the relative diagnostic tests accuracy of hrHPV testing on self- and urine samples compared to hrHPV testing on cervical samples taken by a clinician. Furthermore, the participating women will receive also a questionnaire which can give insights into the attitudes and preferences of the women with regard to the self-sampling devices.

Official Title
-----------------
Validation of Human Papillomavirus Assays and Collection Devices for HPV Testing on Self-samples and First-void Urine Samples (VALHUDES)

Conditions
-----------------
Cervical Intraepithelial Neoplasia Grade 2/3

Intervention / Treatment
-----------------
* Device: Colli-Pee
* Device: Multi-Collect Swab
* Device: Evalyn Brush
* Device: Qvintip
* Diagnostic Test: Abbott RealTime High Risk HPV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with previous abnormal cervical cancer screening test results Women between the ages of 25 and 64 Exclusion Criteria: Hysterectomised women Women with known pregnancy Non-consenting women Women that are not able to understand and to sign the informed consent

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
Female

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Colli-Pee|First, two first-void urine samples will be collected with the Colli-Pee device (Novosanis NV, Wijnegem, Belgium) at home, the day before a visit to the colposcopy centre at a gynecology clinic.|
|Device: Multi-Collect Swab|At the colposcopy clinic, one vaginal self-sample will be collected with the Multi-Collect Swab (Abbott GmbH & Co. KG, Wiesbaden, Germany).|
|Device: Evalyn Brush|Another vaginal self-sample will be collected also at the colposcopy centre either with the Evalyn Brush (Rovers Medical Devices B.V., Oss, Netherlands)|
|Device: Qvintip|or with Qvintip (Aprovix AB, Uppsala, Sweden).|
|Diagnostic Test: Abbott RealTime High Risk HPV|The hrHPV assay used, will be the Abbott PCR (Abbott GmbH & Co. KG, Wiesbaden, Germany), which detects separately DNA of HPV16 and HPV18, as well as the pool of twelve other hrHPV types (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The accuracy of this PCR assay for the detection of CIN2+ will be determined on all samples: on the first urine sample and on the vaginal and cervical samples. Furthermore, it is possible that in the future other assays will be validated.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical accuracy | • Relative sensitivity and specificity of hrHPV testing on first-void urine vs clinician-collected samples. | up to 18 months | 
| Clinical accuracy | • Relative sensitivity and specificity of hrHPV testing on vaginal self-samples vs clinician-collected samples. | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical accuracy | • Absolute sensitivity and specificity for finding underlying CIN2+ of hrHPV testing on urine, self- and clinician-collected samples. | up to 18 months | 
| Clinical accuracy | • Relative sensitivity and specificity of hrHPV testing on samples taken with the Qvintip vs the Evalyn Brush (non-matched comparison) and on urine samples vs the different vaginal self-samples (matched comparison) | up to 18 months | 
| Clinical accuracy | • An intermediate statistical analysis will be performed after that 100 patients are included to verify whether all processes run as expected. Possible protocol adjustments may be considered after this intermediate analysis. | up to 18 months | 
| Analytical performance | • Concordance of the presence of hrHPV and of the partial HPV genotyping results applied on urine, self- and clinician-collected samples; correlation in viral load (expressed as cycle number values) between samples. | up to 18 months | 
| Analytical performance | • Positivity rates for beta-globin in the different types of samples. | up to 18 months | 
| Analytical performance | • Correlation of cycle number values for HPV16, HPV18, other hrHPV and beta-globin between the different types of samples. | up to 18 months | 
| Acceptance and preferences | • Acceptance of self-sampling, preferences of women (assessed from a questionnaire and from participation rate [number of women who participate/number of women approached]). | up to 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Self-Sampling, HPV Testing, Diagnostic Test Accuracy, Cervical Intraepithelial Neoplasia, Urine, Cervical Cancer Screening