Comparing molecular and imaging techniques for the detection of womb cancer in black women
| ISRCTN | ISRCTN12265297 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12265297 |
| IRAS number | 53431 |
| Secondary identifying numbers | IRAS 53431, CPMS 30876 |
- Submission date
- 23/01/2024
- Registration date
- 16/02/2024
- Last edited
- 03/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
This study aims to improve the diagnosis of womb (endometrial) cancer amongst black women in the UK. This is the fourth most common cancer in the UK and black women are more likely to be diagnosed at an advanced stage of disease. This worsens their outcomes.
There is currently no screening programme for womb cancer. Most women will present symptomatically with abnormal vaginal bleeding which is considered a red flag. Only a small number of these women will have womb cancer, but clinical assessment is focused on correctly identifying these women for prompt diagnosis and treatment.
In the UK, the gold standard for assessing these women is using transvaginal ultrasound. This approach can sometimes be inaccurate and result in either missed diagnoses, or the need for multiple invasive confirmatory diagnostic tests, in order to detect each case of womb cancer.
The novel WID™-qEC test is a molecular test based on cervical and vaginal swab specimens. It has been shown to be highly sensitive and specific for diagnosing womb cancer, but not adequately studied in black women.
The aim of this study is to assess the performance of the WID™-qEC test in detecting womb cancer in black women. This will be compared with ultrasound triage and the diagnostic accuracy of the two approaches will be compared.
Who can participate?
Women aged 50 years or above who present to rapid access Gynaecology clinics with abnormal vaginal bleeding warranting further investigation. Women should self-identify as belonging to one of the following ethnic groups:
1. Black, African, or Caribbean
2. Mixed/multiple ethnic groups (Black African or Caribbean and other ethnic background)
What does the study involve?
Each participant will require two swabs. One is a self-collected swab from the lower vagina. Instructions for how to collect this will be given to participants. The second is a high vaginal swab from behind the cervix, visualised when the participant undergoes a speculum examination as part of their clinical assessment. Samples will be labelled with an anonymised barcode sticker.
What are the possible benefits and risks of participating?
This study is altruistic, there is no remuneration to take part. Risks include a small amount of bleeding and discomfort from the cervical brush sample. Participants will not personally benefit from taking part in the study.
Where is the study run from?
1. EGA Institute for Women's Health, University College London (UK)
2. European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, (Austria)
When is the study starting and how long is it expected to run for?
October 2014 to December 2026
Who is funding the study?
1. The Eve Appeal charity (UK)
2. University Innsbruck (Austria)
Who is the main contact?
Dr Ojone Illah, o.illah@ucl.ac.uk
Contact information
Principal Investigator
Department of Women’s Cancer
EGA Institute for Women’s Health
University College London
72 Huntley Street
London
WC1E 6AU
United Kingdom
| Phone | +44 (0)203 108 2003 |
|---|---|
| m.widschwendter@ucl.ac.uk |
Public, Scientific
Department of Women’s Cancer
EGA Institute for Women’s Health
University College London
72 Huntley Street
London
WC1E 6AU
United Kingdom
| Phone | +44 (0)203 108 2003 |
|---|---|
| o.illah@ucl.ac.uk |
Scientific
Department of Women’s Cancer
EGA Institute for Women’s Health
University College London
72 Huntley Street
London
WC1E 6AU
United Kingdom
| Phone | +44 (0)203 108 2003 |
|---|---|
| allison.jones@ucl.ac.uk |
Scientific
Department of Women’s Cancer
EGA Institute for Women’s Health
University College London
72 Huntley Street
London
WC1E 6AU
United Kingdom
| Phone | +44 (0)203 108 2003 |
|---|---|
| iona.evans@ucl.ac.uk |
Scientific
Department of Women’s Cancer
EGA Institute for Women’s Health
University College London
72 Huntley Street
London
WC1E 6AU
United Kingdom
| Phone | +44 (0)203 108 2003 |
|---|---|
| d.reisel@ucl.ac.uk |
Study information
| Study design | Multi-centre observational prospective cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A comparative study of epigenetic analysis and ultrasonography for endometrial cancer detection in black women with abnormal vaginal bleeding |
| Study acronym | EPISURE-B |
| Study objectives | For most cancers, black individuals are disproportionately affected, often having higher mortality compared to other ethnic groups. Endometrial cancer is not an exception, with black women having higher mortality rates from the disease compared to white women. One key contributing factor to this disparity is an increased likelihood of advanced disease stage at diagnosis in black women. Current clinical pathways investigate women with abnormal vaginal bleeding using transvaginal ultrasound as a means of assessing the endometrium. This is currently the gold standard test for endometrial cancer triage. For several reasons, including an increased prevalence of fibroids in black women, the sensitivity of transvaginal ultrasound for endometrial cancer detection in black women is much lower than in white women. Additionally, ultrasound does not reliably identify women without endometrial cancer, which results in women with benign disease often undergoing multiple invasive investigations. A test with a higher specificity than first-line transvaginal ultrasonography would more accurately identify and triage women with and without endometrial cancer. In black women, this may result in earlier diagnosis and improved clinical outcomes. The WID™-qEC is a novel test, developed to test for endometrial cancer on cells collected from cervicovaginal swabs. The test has been shown to detect endometrial cancer with a high sensitivity and specificity, by measuring specific DNA methylation signals at several CpGs across two key genes which are important for endometrial cancer carcinogenesis. Preliminary studies of the WID™-qEC test have been positive, but with a participant pool consisting of predominantly European, Caucasian women, it is necessary that the test is validated in black women. The primary objective of this study is to test the diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) of the WID™-qEC test in comparison to TVS in the detection of EC in black women presenting with abnormal vaginal bleeding. The secondary objectives of the study are as follows. 1. To assess the number of additional procedures required in WID™-qEC true-positive and false-negative patients to reach a histological diagnosis. 2. Stage, histology, and grade of disease at diagnosis, and relation to WID™-qEC result 3. Rates of inconclusive results with both WID™-qEC test and TVS. 4. Compare the yield of the WID™-qEC test in self-collected (low) vaginal samples versus in clinician-collected (high) vaginal samples. It is hypothesised that the WID™-qEC test can diagnose endometrial cancer with a high accuracy in black women presenting with abnormal vaginal bleeding, and thus can reliably be used as a triage test for endometrial cancer in this population. |
| Ethics approval(s) |
Approved 27/10/2014, NRES Committee London - Surrey Borders (Skipton House, 80 London Road, London, SE1 6LH, United Kingdom; +44 (0)207 104 8104; nrescommittee.london-surreyborders@nhs.net), ref: 14/LO/1633 |
| Health condition(s) or problem(s) studied | Endometrial cancer |
| Intervention | This study will evaluate the accuracy of a novel epigenetic test, the WID™-qEC test, in detecting endometrial cancer in black women. WID™-qEC test performance will be assessed using vaginal and cervicovaginal swabs from 200 black women who present to two tertiary hospitals in London with abnormal vaginal bleeding, with a suspicion of endometrial cancer. The comparator test will be transvaginal ultrasonography, with histology (endometrial biopsy) serving as the gold standard for diagnosis. Using these results, we will calculate the diagnostic accuracy of the WID™-qEC test for the detection of endometrial cancer in black women. The study procedures will include: 1. Cervicovaginal sampling The study requires two cervicovaginal samples to be taken using a Copan swab and placed into an eNAT® preservation tube. The first sample is to be self-collected, i.e., by the patient themselves after instructions given. This will be a lower vaginal swab. The second sample will be collected by the clinician prior to any other vaginal manipulation (e.g., transvaginal ultrasound, cervical smear, etc). A standard Cusco speculum will be used for access to visualise the cervix. Water-soluble gel lubricant may be used to reduce any discomfort, but this is not to be applied to the tip of the speculum. The clinician will then take a sample from the posterior vaginal fornix using a Copan swab. Once obtained, this sample will be placed in the eNAT® preservation medium and labelled with a unique participant ID code. Cervicovaginal samples will be subject to the index test, the WIDTM-qEC test. This test measures the ΣPMR of methylation at three CpGs across two genes. Predefined thresholds will be applied to signify a positive or negative test. 2. Ultrasonography This represents the comparator test. All women are to undergo a transvaginal ultrasound by a trained clinician. Where a clear sonographic view of the endometrium and uterine cavity is difficult to obtain, additional sonographic techniques will be offered. These may include transabdominal and transrectal sonography. Sonographic assessment must include the following: 1. Measurement of endometrial thickness 2. Doppler ultrasonography 3. Description of any associated anomalies 4. A subjective pattern recognition impression Ultrasound examiners will classify findings according to the following two criteria: 1. Endometrial thickness (ET): ET <4.0 mm (negative), ET ≥4.0 mm (positive), or uninformative and, 2. Subjective pattern recognition (based on morphological features and colour Doppler findings): likely benign, likely cancer or inconclusive. Both outcomes will be recorded immediately after the ultrasound procedure and prior to obtaining histology and/or any other procedures. 3. Endometrial sampling In women with a uniformly thickened endometrium of at least 4 mm, endometrial sampling via pipelle biopsy will be offered in the outpatient setting. If declined or unsuccessful, a hysteroscopic biopsy will be offered. In women with focal pathology warranting histological assessment, such as an endometrial polyp, a hysteroscopy and biopsy and/or polypectomy will be offered. All samples will be histologically assessed, and histology will act as the reference standard for the study. Where other histological samples are used to make a diagnosis, such as a biopsy from a distant organ or a hysterectomy, these will be considered when determining the final diagnosis. The tissue will be examined by the histopathologists who will assign a tissue diagnosis of EC or no EC. |
| Intervention type | Other |
| Primary outcome measure | The 'real world' diagnostic performance (sensitivity, specificity, positive and negative predictive values) of the WIDTM-qEC test as first-line triage for a cohort of women from the ‘Black’ and ‘Black Mixed’ ethnic groups referred with abnormal vaginal bleeding. WIDTM-qEC test and ultrasound diagnostic performance will be measured when the patient initially presents to the hospital. Vaginal sample is taken at the time of the initial ultrasound scan. Where endometrial sampling or hysterectomy is required, this will typically occur within 4 weeks. |
| Secondary outcome measures | 1. Number of ultrasound and other imaging investigations required in WIDTM-qEC true-positive and false-negative patients to reach a histological diagnosis, measured using ultrasound +/- Pipelle biopsy at initial presentation, and hysteroscopy/endometrial biopsy and/or hysterectomy 1-4 weeks later, respectively. 2. Stage, histology, and grade of disease at diagnosis and relation to WIDTM-qEC and TVUS findings, measured using surgical staging of histopathology specimens after a hysterectomy (+/- other procedures) has been performed, typically within 4 weeks. 3. Rates of inconclusive results with both the WIDTM-qEC test and TVUS, measured using the number of diagnostic procedures carried out throughout the patient’s journey to assess the cause of abnormal vaginal bleeding. |
| Overall study start date | 27/10/2014 |
| Completion date |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 50 Years |
| Sex | Female |
| Target number of participants | 400 |
| Key inclusion criteria | 1. Women aged 50 years and above 2. Experiencing abnormal vaginal bleeding warranting ultrasound examination 3. Able to give informed consent 4. Fall under one of the following self-defined ethnic categories: 4.1. Black, African, or Caribbean 4.2. Mixed/ multiple ethnic groups (Black African or Caribbean and other ethnic background) |
| Key exclusion criteria | 1. Current hormone replacement therapy (HRT) use 2. History of hysterectomy |
| Date of first enrolment | 23/01/2024 |
| Date of final enrolment | 31/12/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
Great Maze Pond
London
SE1 9RT
United Kingdom
Croydon
CR7 7YE
United Kingdom
Sponsor information
University/education
UCL/UCLH Joint Research Office
250 Euston Road
London
NW1 2PG
England
United Kingdom
| Phone | +44 (0)20 7679 2000 |
|---|---|
| uclh.randd@nhs.net | |
| Website | http://www.ucl.ac.uk/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Charity
No information available
Private sector organisation / Universities (academic only)
- Alternative name(s)
- University of Innsbruck, uibk
- Location
- Austria
Results and Publications
| Intention to publish date | 30/09/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Results of the study will be submitted to high-impact, peer-reviewed journals. |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be available upon request from the principal investigator Prof. Martin Widschwendter (m.widschwendter@ucl.ac.uk). |
Editorial Notes
03/07/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 31/07/2025 to 31/03/2026.
2. The completion date was changed from 31/12/2025 to 31/12/2026.
27/03/2025: The following changes were made to the study record:
1. The target number of participants was changed from 200 to 400.
2. The recruitment end date was changed from 30/03/2025 to 31/07/2025.
3. The study participating centre Croydon University Hospital was added.
04/03/2024: Internal review.
05/02/2024: Study's existence confirmed by the NRES Committee London - Surrey Borders and The Eve Appeal.
