HPV Test of Urine and Self Collected Vaginal Samples for Cervical Cancer Screening Study

Study Overview
=================
Brief Summary
-----------------
This study is a prospective observational study of human papillomavirus (HPV) testing using urine and self-collected vaginal samples for women who have atypical squamous cells of undetermined significance(ASCUS) or low grade squamous intraepithelial lesion(LSIL) on Pap test. Among women who are diagnosed with ASCUS and LSIL, HPV test is performed by collecting urine and self-collected vaginal sample in standardized condition before colposcopy, and evaluation will be performed as a primary screening test with cytology triage.

Detailed Description
-----------------
The samples are collected from patients referred to colposcopy because of prior cervical abnormalities on Pap test such as ASCUS and LSIL. The patient takes at home urine samples on the morning of visit to the colposcopy center. At the colposcopy center, self-collected vaginal samples are taken by the patient herself with a plastic brush (Flocked Swab, manufactured by Noble Bioscience, Inc.). Finally, the gynecologist takes a cervical sample with a plastic brush (Cervical Brush, manufactured by Noble Bioscience, Inc.). Physician collected cervical samples, self-collected vaginal samples and urine samples are used to perform HPV testing with Roche Cobas® 4800 HPV test, Anyplex™ II HPV HR detection kit and Realtime HPV HR-S Detection kit. The Anyplex™ II HPV HR detection kit (manufactured by Seegene. Inc, Korea) is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk. (HR) human papillomavirus (HPV) types in a single tube. The Roche Cobas® 4800 HPV test (manufactured by Cobas) is a novel molecular method based on real-time PCR (RT-PCR), with a fully automated system allowing quick and efficient sample processing. Cobas can detect the human papillomavirus type 16(HPV16), the human papillomavirus type 18(HPV18), 12 other high-risk HPVs (hrHPVs) (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68, as a pooled result), and the β-globin control independently in the same PCR. Realtime HPV HR-S Detection kit (manufactured by Sejong Biomed Co, Korea) is a new, real-time polymerase chain reaction assay to detect HPV 16, HPV 18, 12 other high-risk HPVs (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68). Real-time HPV HR-S Detection Kit is based on accurate real-time PCR method as described, and it can detect 14 kinds of HPV type detection in a single test (HPV 16/18 genotype and others (UDG) -dUTP) system for the prevention of contamination, and a control agent (hemoglobin DNA, a human-derived DNA) as a whole process control was introduced into a high-risk genotype (12 genotypes other than HPV 16/18). It has high sensitivity and specificity for detection of high risk genotypes by increasing the reliability of the results. The main goal of this study is to determine whether HPV testing using urine and self-collected sample is sensitive to detecting precancerous lesions such as cervical intraepithelial neoplasia(CIN)2/3 in patients diagnosed with ASCUS and LSIL on the Pap test. The colposcopy and histological findings will be used as the gold standard. In addition, the relative sensitivity and specificity for detecting HPV16, HPV18 and high risk HPV will be determined for each of the three HPV tests using urine and self-collected samples compared with the HPV tests using physician-collected samples.

Official Title
-----------------
Human Papillomavirus(HPV) Test of Urine and Self Collected Vaginal Samples for Cervical Cancer Screening Study

Conditions
-----------------
ASC-US, LSIL

Intervention / Treatment
-----------------
* Device: Flocked Swab
* Device: Cervical Brush
* Diagnostic Test: HPV assay


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with previous abnormal Pap test results (ASCUS, LSIL) Women between the ages of 20 and 60 Exclusion Criteria: Hysterectomised women Women with known pregnancy Non-consenting women Women that are not able to understand and to sign the informed consent Women who diagnosed and treated for cervical cancer or other malignancies Concurrent diseases that are immunosuppressed or require the use of immune-suppressants

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Flocked Swab|At the colposcopy clinic, vaginal self-sample will be collected with the Flocked Swab (Noble Bioscience, Inc., Korea).|
|Device: Cervical Brush|Physician collected cervical sample will be collected also at the colposcopy center with the Cervical Brush (Noble Bioscience, Inc., Korea).|
|Diagnostic Test: HPV assay|The hrHPV assay used, will be the Roche Cobas® 4800 HPV test, Anyplex™ II HPV HR detection kit and Realtime HPV HR-S Detection kit.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical accuracy | Absolute sensitivity and specificity for finding underlying cervical intraepithelial neoplasia(CIN)2+ of HPV testing(Roche Cobas® 4800 HPV test, Anyplex™ II HPV HR detection kit and Realtime HPV HR-S Detection kit) on urine, self- and clinician-collected samples. | Within 6 months after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical accuracy | Relative sensitivity and specificity of hrHPV testing on vaginal self-samples and urine sample vs clinician-collected samples. | Within 6 months after study completion | 
| Analytical performance | Concordance of the presence of HPV16, 18 and other high risk HPV genotyping results applied on urine, self- and clinician-collected samples | Within 6 months after study completion | 

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