Evaluation of in Vitro Devices on Self-collected Vaginal Swab and Urine Sample for Testing of Human Papilloma Virus

Study Overview
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Brief Summary
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The European VALHUDES study is a Clinical Performance /Diagnostic Test Accuracy Study that aims to evaluate whether HPV testing with new assays performed on self-samples, collected by means of a vaginal and a urine collection device is as accurate to detect cervical pre-cancer as on cliniciantaken cervical samples.

Detailed Description
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Women accessing the Colposcopy Centres for a colposcopy examination and fulfilling the selection criteria will be asked, after written informed consent, to self-collect a first-void urine (with the Colli-Pee device) and a vaginal sample (with the FLOQSwab device), prior to undergoing colposcopy. Just before colposcopic examination, a clinician will also take a cervical sample (with a Cervex-Brush using the same procedure normally adopted for cervical cytology and/or HPV testing. During colposcopy, a colposcopy-targeted biopsy may be taken if appropriate. When according to colposcopy and biopsy results, an excisional treatment of a cervical precancer lesion is needed, the histology of the excised tissue will complete the end point of the study. The colposcopy and histological findings will be used as the gold standard if biopsies are taken. In case of normal satisfactory colposcopic findings without biopsy taking, colposcopy will provide the study outcome. Three new PCR-based HPV 'in vitro diagnostic devices' (Papilloplex, HPV Oncopredict RNA, HPV Oncopredict DNA) developed as part of the SME Instrument Project 'HPV OncoPredict (GA-806551)' will be assessed.

Official Title
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European VALidation of HUman Papillomavirus Assays and Collection DEvices for HPV Testing on Self-samples and Urine Samples

Conditions
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Cervical Intraepithelial Neoplasia Grade 2/3, Neoplasm Cervix, Carcinoma in Situ, Carcinoma Cervix Uterine, Neoplasms, Neoplasms by Histologic Type

Intervention / Treatment
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* Device: Self-Collecting Devices
* Diagnostic Test: In Vitro Diagnostic Assays


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women referred to colposcopy evaluation for any reason [i.e. previous history of abnormal cervical screen test results (cytology, HPV test), previous abnormal colposcopy] Ability to understand and sign the informed consent Informed consent given Exclusion Criteria: Age < 25 or > 65 years Past history of hysterectomy Women with known pregnancy Pregnancy within last 3 months Vulnerable patient: a patient who is or may be for any reason unable to take care of him or herself, or unable to protect him or herself against significant harm or exploitation Simultaneous involvement in any other research project

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Self-Collecting Devices|FLOQSwab (Copan) Colli-Pee (Novosanis)|
|Diagnostic Test: In Vitro Diagnostic Assays|Papilloplex (GeneFirst) HPV Oncopredict DNA (Hiantis) HPV Oncopredict RNA (GeneFirst)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative accuracy urine vs clinician-collected samples | Relative sensitivity and specificity of each hrHPV DNA assay for detection of cervical intraepithelial neoplasia of grade II or worse (CIN2+) on urine vs on clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Relative accuracy self-collected vaginal vs clinician-collected samples | Relative sensitivity and specificity of each hrHPV DNA assay for detection of cervical intraepithelial neoplasia of grade II or worse (CIN2+) on self-collected vaginal vs on clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute accuracy for each sample type | Absolute clinical sensitivity and specificity for finding underlying CIN2/3+ of the investigated hrHPV assays applied on each sample. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Absolute accuracy among hrHPV DNA-positive women | Absolute clinical sensitivity and specificity using HPV OncoPredict RNA among women with hrHPV DNA-positive result on one of the self-samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Concordance of presence or absence of HPV genotypes between different sample types | Concordance of presence of hrHPV and of HPV genotypes between urine, vaginal and clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Correlation viral load signals between different sample types | Correlation of genotype-specific viral load signals between urine, vaginal and clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Concordance of presence or absence of internal control gene between different sample types | Concordance of positivity for the human cellular control between urine, vaginal and clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Correlation internal control gene signals between different sample types | Correlation of signals for the human internal control gene between urine, vaginal and clinician-collected samples. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Positivity rates human control gene | Positivity rates for human cellular control in the different sample types. | One day, with possible extension if excision biopsy is planned based on the coloposcopy/histology outcome of tissue specimens collected at the enrolment visit. | 
| Questionnaire for the acceptance of self-collection | Women's acceptance and preference regarding urine collection, vaginal self-sampling or collection by a clinician will be assessed through a questionnaire. | One day, at the day of colposcopy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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self-sampling, HPV testing, Diagnostic Test Accuracy, Cervical Intraepithelial Neoplasia, Urine, Cervical Cancer Screening