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

Cervical Intraepithelial Neoplasia Grade 2/3 Clinical Trial

— VALHUDES  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03064087
• Other study ID #: WIV-ISP_2017_001
• Status: Active, not recruiting
• Start date: December 29, 2017
• Est. completion date: November 17, 2027

Study information

• Verified date: March 2023
• Source: Sciensano
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: November 17, 2027
• Est. primary completion date: December 31, 2024
• Gender: Female
• Age group: 25 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Intraepithelial Neoplasia
• Cervical Intraepithelial Neoplasia Grade 2/3
• Neoplasms

Intervention

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.
• 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).
• 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)
• 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.

Locations

Country	Name	City	State
Belgium	UZ Antwerp	Antwerp
Belgium	UZ Brussels	Brussels	Brussels Capital Region
Belgium	UZ Ghent	Ghent	East Flanders
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Heilig Hart Ziekenhuis Tienen	Tienen	Flemish Brabant

Sponsors (7)

Lead Sponsor	Collaborator
Marc Arbyn	Algemeen Medisch Laboratorium, Regionaal Ziekenhuis Heilig Hart Tienen, Universitair Ziekenhuis Brussel, Universiteit Antwerpen, University Hospital, Antwerp, University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

References & Publications (5)

Arbyn M, Castle PE. Offering Self-Sampling Kits for HPV Testing to Reach Women Who Do Not Attend in the Regular Cervical Cancer Screening Program. Cancer Epidemiol Biomarkers Prev. 2015 May;24(5):769-72. doi: 10.1158/1055-9965.EPI-14-1417. Epub 2015 Feb 24. — View Citation

Arbyn M, Snijders PJ, Meijer CJ, Berkhof J, Cuschieri K, Kocjan BJ, Poljak M. Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin Microbiol Infect. 2015 Sep;21(9):817-26. doi: 10.1016/j.cmi.2015.04.015. Epub 2015 May 1. — View Citation

Arbyn M, Verdoodt F, Snijders PJ, Verhoef VM, Suonio E, Dillner L, Minozzi S, Bellisario C, Banzi R, Zhao FH, Hillemanns P, Anttila A. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 2014 Feb;15(2):172-83. doi: 10.1016/S1470-2045(13)70570-9. Epub 2014 Jan 14. — View Citation

Verdoodt F, Jentschke M, Hillemanns P, Racey CS, Snijders PJ, Arbyn M. Reaching women who do not participate in the regular cervical cancer screening programme by offering self-sampling kits: a systematic review and meta-analysis of randomised trials. Eur J Cancer. 2015 Nov;51(16):2375-85. doi: 10.1016/j.ejca.2015.07.006. Epub 2015 Aug 18. — View Citation

Vorsters A, Van den Bergh J, Micalessi I, Biesmans S, Bogers J, Hens A, De Coster I, Ieven M, Van Damme P. Optimization of HPV DNA detection in urine by improving collection, storage, and extraction. Eur J Clin Microbiol Infect Dis. 2014 Nov;33(11):2005-14. doi: 10.1007/s10096-014-2147-2. Epub 2014 Jun 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical accuracy	• Relative sensitivity and specificity of hrHPV testing on first-void urine vs clinician-collected samples.	up to 18 months
Primary	Clinical accuracy	• Relative sensitivity and specificity of hrHPV testing on vaginal self-samples vs clinician-collected samples.	up to 18 months
Secondary	Clinical accuracy	• Absolute sensitivity and specificity for finding underlying CIN2+ of hrHPV testing on urine, self- and clinician-collected samples.	up to 18 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Analytical performance	• Positivity rates for beta-globin in the different types of samples.	up to 18 months
Secondary	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
Secondary	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