Evaluating the Visual Appearance of Cervical Lesions in Relation its Histological Diagnosis, Human Papillomavirus Genotype and Other Viral Parameters: A Prospective Cohort Study.|
|- candidate number||12869|
|- NTR Number||NTR3464|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-jun-2012|
|- Secondary IDs||10-023 METC ZWH|
|- Public Title||Evaluating the Visual Appearance of Cervical Lesions in Relation its Histological Diagnosis, Human Papillomavirus Genotype and Other Viral Parameters: A Prospective Cohort Study.|
|- Scientific Title||Evaluating the Visual Appearance of Cervical Lesions in Relation its Histological Diagnosis, Human Papillomavirus Genotype and Other Viral Parameters: A Prospective Cohort Study.|
|- ACRONYM||EVAH study|
|- hypothesis||In case of multiple HPV genotype infections on the cervix only one HPV type is found on lesion level.|
|- Healt Condition(s) or Problem(s) studied||Cervical intraepithelial neoplasia (CIN), Human Papilloma Virus (HPV)|
|- Inclusion criteria||1. An abnormal cytological test result;|
2. 18 years of age or older;
3. Written informed consent prior to enrolment;
4. Sufficient knowledge of the Dutch/Spanish language;
5. The intention to comply with the requirements of the protocol.
|- Exclusion criteria||1. History of surgery on the cervix;|
2. Previous pelvic radiotherapy;
3. Pregnancy or pregnant in the last 3 months;
4. Actually breast-feeding or breast-feeding in the last 3 months;
5. Diagnosis of cervix carcinoma.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||29-jul-2010|
|- planned closingdate||31-dec-2012|
|- Target number of participants||600|
|- Interventions||Not applicable. This is an observational study which follows the regular clinical procedures.|
|- Primary outcome||In the follow-up period of the study, the endpoint will be the histologically confirmed recurrence of a
high-grade cervical lesion, defined as CIN 2 or 3, AIS or worse, or after the colposcopic examination
24 months after the first visit has been performed.|
|- Secondary outcome||N/A|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD. J. Marel, van der|
|- CONTACT for SCIENTIFIC QUERIES||MD. J. Marel, van der|
|- Sponsor/Initiator ||DDL Diagnostic Laboratory|
(Source(s) of Monetary or Material Support)
|DDL Diagnostic Laboratory, Rijswijk, The Netherlands|
|- Brief summary||Rationale:|
Persistent infection with high-risk human papillomavirus (HR-HPV) types is necessary for the development of cervical cancer. One of the most important tools to reduce the incidence of this disease is the early diagnosis and treatment of its precursor lesions, e.g. by cervical cytology. In women with abnormal cytology, colposcopic evaluation is used to obtain cervical biopsies for histological confirmation. However, the sensitivity of this approach is limited. DNA techniques for detecting HR-HPV have shown to be effective in the clinical management of patients with cervical
disease. The main contribution of these techniques is their high sensitivity and negative predictive value. Nonetheless, this increase in sensitivity is accompanied by a notable reduction in specificity; therefore a considerable number of transient infections are detected, which have only minimal chance of progression, but nevertheless require a thorough survey. Consequently, other specific markers than the presence of HR-HPV, such as HPV genotype or molecular transformation markers are needed to identify patients at significant risk of progression and improve their management.
To date, 20–40% of HPV-positive women are reported to be infected with multiple HPV types. Detailed understanding of the natural history and dynamics of HPV infection, and the pathogenic effect of
infection with multiple types is crucial to monitor the impact of the recently introduced HPV-vaccination on the risk of infection with individual HPV types.
In case abnormal cytology is diagnosed in a woman, she is referred for colposcopy. Digital colposcopic imaging has been developed in the last decade and allows the recording of high quality digital photographs for several purposes. Compared to conventional colposcopy it provides greater objectivity to evaluate colposcopic images and to quantify the findings. Furthermore it provides the
opportunity of monitoring progression or regression of the observed lesions. Digital colposcopy with a system to annotate the lesions of interest, gives the opportunity to study the correlation between the characteristics of colposcopic image, histological diagnosis, HPV genotype(s) and molecular transformation markers.
Recently the Laser Capture Microdissection (LCM) method has been applied to cervical biopsy specimens. This technique allows molecular assessment of selected cell populations, e.g. HPV status, that are histologically or pathologically distinct although topographically close. LCM can give more insight in the pathogenesis of cervical premalignant lesions.
1. Evaluate colposcopic visual appearance of cervical lesions in relation to its histological
substrate, HPV genotype(s) and molecular parameters;
2. Study cervical disease on the lesion level using HPV genotyping and other viral parameters.
1. Determine the incremental benefit of taking multiple biopsies to detect CIN;
2. Compare visual assessment and biopsy placement between expert colposcopists;
3. Participate in a world-wide collaboration to create a database of cervical images with clinical outcomes and to set standards of colposcopic assessment and biopsy placement;
4. Determine the predictive value of HPV self-sampling in the management and follow-up of women with CIN;
5. Study the clinical value of HPV self-sampling compared to physician obtained HPV testing.
This study is designed as a prospective multicenter observational cohort study.
The study population consists of 600 women aged 18 years and above, referred to the gynecologic outpatient clinic of Reinier de Graaf hospital in Voorburg, the Netherlands or Hospital Clnic in
Barcelona, Spain, for colposcopic evaluation of an abnormal Pap smear.
At all clinical visits, colposcopy will be performed in which a digital image of the cervix will be taken and lesions will be annotated in a digital system. A cervical scrape will be taken by the physician for cytology, HR-HPV testing and evaluating biomarkers for cervical carcinogenesis. A cervico-vaginal self-sampling test will be performed by the women at the first visit. This sample will be tested for HRHPV as well. If a suspect lesion is visible, up to four biopsies will be taken after digital annotation. If histology shows a high grade lesion (CIN 2 or 3), a loop electrosurgical excision procedure (LEEP) will be performed in a subsequent visit according to the national guidelines. If no suspect lesion is visible, one random biopsy will be taken. The follow-up period will concede 24 months in total, in which the women visit the outpatient clinic every six months. A cervical smear and colposcopy will be performed. Before every follow-up visit the women perform a self-sampling test.
|- Main changes (audit trail)|
|- RECORD||6-jun-2012 - 20-jun-2012|
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