CASUS: Validation for Detection of Precursor Lesions

Not Applicable

Completed

• Conditions: Cervical Cancer; Human Papilloma Virus; Urine; Cervical Intraepithelial Neoplasia; HPV-Related Cervical Carcinoma

• Registration Number: NCT04530201
• Lead Sponsor: Universiteit Antwerpen

Brief Summary

The goal of the overall CASUS project is to develop the first fully molecular integrated cervical cancer screening approach, based on first-void urine as an easily accessible and non-invasive source of biomarkers. In contrast to current screening modalities, the CASUS approach will identify women with clinically relevant disease in need of treatment using only a single sample that can be collected at home (one-step triage).

Detailed Description

CASUS work package 4 (WP4):

The main aim of this study is to validate the HPV-Risk assay (Self-screen, The Netherlands) followed by multiplex methylation specific quantitative PCR (qMSP, VU University Medical Center, The Netherlands) on first-void urine (Colli-Pee Small Volumes (10 mL) device, Novosanis, Belgium) of HPV positive women for detection of clinically relevant precursor lesions by sampling a cohort of women referred for colposcopy. The number of women in this cohort will allow us to clinically validate the use of the HPV-Risk/qMSP assay in DNA extracts of first-void samples after optimization of sample volume, internal process control, and DNA extraction method (Centre for the Evaluation of Vaccination, University of Antwerp, Belgium).

Study Timeline

• Study Start: 2020-08-20
• Study First Submitted: 2020-08-24
• Study First Submitted QC: 2020-08-24
• Study First Posted: 2020-08-28
• Primary Completion: 2021-10-20
• Study Completion: 2022-02-28
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-14
• Last Update Posted: 2022-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 332

Inclusion Criteria

• Female
• 25 years until 64 years old
• Referred to colposcopy due to a single/multiple (probable) high-risk HPV infection and/or abnormal cervical squamous intraepithelial/glandular lesion.
• Gives informed consent to the research team at the clinical study site to contact his/her general practitioner and/or gynaecologist to access details of the participants HPV test results and cervical screening history.
• Is able to understand the information brochure/what the study is about.

Exclusion Criteria

• Women that underwent hysterectomy
• Pregnant women
• Treatment for cervical cancer in the last 6 months before participation in the study
• Participating in an interventional clinical study (where e.g. a medical device, drug, or vaccine is evaluated) at the same time of participating in this study. Participation in another observational or low-interventional clinical study at the same time is allowed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
HPV DNA (HPV16, HPV18, other high-risk HPV (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68)) measured using the HPV-risk assay (Self-Screen BV).	Through study completion, an average of 1 year	Analytical test results: HPV DNA (HPV16, HPV18, other high-risk HPV (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68)) concentrations \[cycle threshold values\] in first-void urine samples from all study participants.; Clinical test accuracy: HPV DNA (HPV16, HPV18, other high-risk HPV (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68)) test outcomes \[positive, negative\] in first-void urine samples from all study participants compared to the gold standard reference test for cervical cancer screening; i.e. histology \[Cervical Intraepithelial Neoplasia grade 0-3+\].
Methylation ratio of a host cell gene marker panel (PreCursor-U+) measured using quantitative methylation specific PCR (qMSP).	Through study completion, an average of 1 year	Analytical test results: Methylation levels of a host cell gene marker panel (PreCursor-U+) reported in a methylation ratio \[(2\^-deltaCT \*100) with CT being cycle threshold values\] in first-void urine samples from all study participants.; Clinical test accuracy: Methylation panel (PreCursor-U+) test outcomes \[positive, negative\] in first-void urine samples from all study participants compared to the gold standard reference test for cervical cancer screening; i.e. histology \[Cervical Intraepithelial Neoplasia grade 0-3+\].

Secondary Outcome Measures

Name	Time	Method
Human DNA (GAPDH)	Through study completion, an average of 1 year	Human DNA (GAPDH) concentrations \[cycle threshold values\] in first-void urine samples from all study participants measured by quantitative PCR (qPCR).
Internal control DNA (IC DNA)	Through study completion, an average of 1 year	Internal control DNA (IC DNA) concentrations \[cycle threshold values\] in first-void urine samples from all study participants measured by quantitative PCR (qPCR).
Human DNA (Beta-globin)	Through study completion, an average of 1 year	Human DNA (Beta-globin) concentrations \[cycle threshold values\] in first-void urine samples from all study participants measured using the HPV-risk assay (Self-Screen BV).
Human DNA reference gene (ACTB)	Through study completion, an average of 1 year	Human DNA reference gene (ACTB) concentrations \[cycle threshold values\] in first-void urine samples from all study participants measured by quantitative methylation specific PCR (qMSP).

Trial Locations

Locations (3)

Vrouwenkliniek - Universitair Ziekenhuis Gent (UZ Gent); 🇧🇪 Gent, Oost-Vlaanderen, Belgium

Femicare VZW & Departement Verloskunde & Gynaecologie - Regionaal Heilig Hart Ziekenhuis Tienen; 🇧🇪 Tienen, Vlaams-Brabant, Belgium

Gynécologie-obstétrique - CHU de Liège; 🇧🇪 Liège, Belgium