Urine human papillomavirus (HPV) testing for cervical pre-cancer screening
| ISRCTN | ISRCTN13132810 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13132810 |
| IRAS number | 286415 |
| Secondary identifying numbers | IRAS 286415, CMPS 47016 |
- Submission date
- 27/01/2021
- Registration date
- 18/02/2021
- Last edited
- 17/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English Summary
Current plain English summary as of 18/01/2022:
Background and study aims
Cervical screening can save lives from cervical cancer, yet only 7 in 10 women in the UK attend screening, the lowest rate in 20 years. Reasons include embarrassment, fear of examination and inconvenience. Cervical screening is carried out by collecting cells from the cervix (neck of the womb) with a soft brush. These cells are tested for a virus known to cause cancer called human papillomavirus (HPV). If HPV is detected, the cells are examined under the microscope. If they look abnormal, the woman is referred to colposcopy clinic, where cells that are found to be ‘pre-cancerous’ (cells with the potential to become cancer cells) are identified and treated. To increase screening rates, vaginal ‘self-sampling’ has been tried, where a woman collects cells from her vagina at home and returns the sample by post, however only 1 in 10 women return the sample. There is therefore an urgent need for new ways to reverse declining rates of cervical screening.
We have developed a urine test that can detect HPV. This test has the potential to remove many of the current barriers to screening and could substantially increase the number of women attending. This study will see if a urine test can accurately identify women with cervical pre-cancer and those who continue to be HPV positive after treatment by comparing HPV detection rates in urine and cervical samples.
Who can participate?
Women, or people with a cervix attending gynaecology and colposcopy clinics at Manchester University NHS Foundation Trust for cervical screening or management of abnormal cervical screening
What does the study involve?
Participants will be asked to provide a first void urine sample prior to a routine cervical screening test. Individuals requiring test of cure cervical screening will also be asked to self-collect a vaginal sample. Samples will be tested for high-risk HPV and urine/cervical HPV-positive samples will undergo methylation testing. Women will be asked to complete a short questionnaire to understand views and preferences of current cervical screening attendees. This study will help establish whether the clinical performance of urine testing is sufficient to recommend its use as an NHS cervical screening test.
What are the possible benefits and risks of participating?
There are no immediate benefits to the individual taking part in this study. We will use the results to help us know whether urine HPV testing could be a reasonable alternative to routine cervical screening. This could encourage more women to participate in cervical screening in the future.
We do not expect there to be any side effects by taking part. Some participants may find a smear test uncomfortable, painful or embarrassing. For some women the smear test will be taken as part of their routine care investigations anyway.
Where is the study run from?
Manchester University NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2020 to June 2026
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Suzanne Carter (public), suzanne.carter@manchester.ac.uk
Prof. Emma Crosbie (scientific), emma.crosbie@manchester.ac.uk
Contact information
Public
The University of Manchester
Division of Cancer Sciences
School of Medical Sciences
Faculty of Biology, Medicine and Health
St Mary's Hospital
Manchester
M13 9WL
United Kingdom
| Phone | +44 (0)161 701 6941 |
|---|---|
| suzanne.carter@manchester.ac.uk |
Scientific
The University of Manchester
Division of Cancer Sciences
School of Medical Sciences
Faculty of Biology, Medicine and Health
St Mary's Hospital
Manchester
M13 9WL
United Kingdom
 ORCID ID |
0000-0003-0284-8630 |
|---|---|
| Phone | +44 (0)161 701 6942 |
| emma.crosbie@manchester.ac.uk |
Study information
| Study design | Observational cross-sectional study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional 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 | Urine HPV testing for cervical screening in women: Alternative CErvical Screening (ACES) |
| Study acronym | ACES |
| Study hypothesis | The aims of this study are to optimise urine HPV testing, assess urinary HPV +/- methylation testing for the detection of CIN2+ in a colposcopy referral population, and establish the acceptability of urine HPV testing as an alternative to routine cervical screening. |
| Ethics approval(s) | Approved 16/11/2020, North West Great Manchester West Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)207 104 8068; gmwest.rec@hra.nhs.uk), ref: 20/NW/0389 |
| Condition | Diagnostic accuracy of urine HPV testing for cervical screening |
| Intervention | Current intervention as of 11/04/2023: This study will see if a urine test can accurately identify women with cervical pre-cancer and those who continue to be HPV-positive after treatment by comparing HPV detection rates in urine and cervical samples. Matched urine and cervical samples will be tested for high-risk HPV. HPV-positive samples will undergo methylation testing. Vaginal self-samples will also be taken in a sub-set of participants undergoing Test of Cure. Prior to routine clinic procedures, we will collect a voided urine sample and an optional self-collected vaginal sample. Samples will be self collected at hospital, in the privacy of the clinic bathroom, or by the participant in their own home. Collection must be done before routine procedures to mirror what would happen in ‘real life’ if a urine test were to replace routine screening. It must also be done on the same day as the cervical sample, to preclude changes in viral status between sampling time points affecting the validity of the results. We will then take a routine cervical screening (‘Pap’ smear) sample if one is not taken as part of the participant’s routine care. We will directly compare HPV detection rates at standard concentration thresholds, concordance between urine and matched cervical samples and CIN2+ detection rates in urine samples collected with and without Colli-Pee™ or other CE marked urine collection device. We will also compare HPV detection rates for vaginal self sampling, in those have provided a sample. If the participant attends for a follow up visit (e.g. for treatment after initial assessment), we may ask them to provide a second or third set of samples, if they consent. This will help us understand more about how well the urine test could work during the natural history of HPV infection and the management of abnormal smears. Participants will answer a short cross-sectional acceptability questionnaire to gauge views on urine and vaginal testing for cervical screening. Those who decline participation will be asked to record their reasons on a short questionnaire. This is entirely optional. First the researchers will optimise urine collection and processing using various collection devices and preservative solutions. Next, they will carry out a randomised controlled trial of urine collection using a sterile pot or a 10ml Colli-Pee™ urine collection device + Preservative. A selection of participant samples may also be tested using a variety of NHSCSP-approved HPV tests without the need for randomisation and/or asked to provide a vaginal self sample. _____ Previous intervention as of 18/01/2022: This study will see if a urine test can accurately identify women with cervical pre-cancer and those who continue to be HPV positive after treatment by comparing HPV detection rates in urine and cervical samples. Matched urine and cervical samples will be tested for high risk HPV. HPV positive samples will undergo methylation testing. Prior to routine clinic procedures, we will collect a voided urine sample. Urine samples will be self collected at hospital, in the privacy of the clinic bathroom, or by the participant in their own home. Urine collection must be done before routine procedures to mirror what would happen in ‘real life’ if a urine test were to replace routine screening. It must also be done on the same day as the cervical sample, to preclude changes in viral status between sampling time points affecting the validity of the results. We will then take a routine cervical screening (‘Pap’ smear) sample if one is not taken as part of the participant’s routine care. We will directly compare HPV detection rates at standard concentration thresholds, concordance between urine and matched cervical samples and CIN2+ detection rates in urine samples collected with and without Colli-Pee™ or other CE marked urine collection device. If the participant attends for a follow up visit (e.g. for treatment after initial assessment), we may ask them to provide a second or third set of samples, if they consent. This will help us understand more about how well the urine test could work during the natural history of HPV infection and the management of abnormal smears. Participants will answer a short cross sectional acceptability questionnaire to gauge views on urine testing for cervical screening. Those who decline participation will be asked to record their reasons on a short questionnaire. This is entirely optional. First the researchers will optimise urine collection and processing using various collection devices and preservative solutions. Next, they will carry out a randomised controlled trial of urine collection using a sterile pot or a 10ml Colli-Pee™ urine collection device + Preservative. A selection of participant samples may also be tested using a variety of NHSCSP-approved HPV tests without the need for randomisation. _____ Previous intervention: This study will see if a urine test can accurately identify cervical pre-cancer by comparing HPV detection rates in urine and cervical samples. Matched urine and cervical samples will be tested for high risk HPV. HPV positive samples will undergo methylation testing. Prior to routine clinic procedures, we will collect a voided urine sample. Urine samples will be self collected at hospital, in the privacy of the clinic bathroom. Urine collection must be done before routine procedures to mirror what would happen in ‘real life’ if a urine test were to replace routine screening. It must also be done on the same day as the cervical sample, to preclude changes in viral status between sampling time points affecting the validity of the results. We will then take a routine cervical screening (‘Pap’ smear) sample if one is not taken as part of the participant’s routine care. We will directly compare HPV detection rates at standard concentration thresholds, concordance between urine and matched cervical samples and CIN2+ detection rates in urine samples collected with and without Colli-Pee™ or other CE marked urine collection device. If the participant attends for a follow up visit (e.g. for treatment after initial assessment), we may ask them to provide a second or third set of samples, if they consent. This will help us understand more about how well the urine test could work during the natural history of HPV infection and the management of abnormal smears. Participants will answer a short cross sectional acceptability questionnaire to gauge views on urine testing for cervical screening. Those who decline participation will be asked to record their reasons on a short questionnaire. This is entirely optional. Added 28/09/2021: First the researchers will optimise urine collection and processing using various collection devices and preservative solutions. Next, they will carry out a randomised controlled trial of urine collection using a sterile pot or a 10ml Colli-Pee™ urine collection device + Preservative. A selection of participant samples may also be tested using a variety of NHSCSP-approved HPV tests without the need for randomisation. |
| Intervention type | Other |
| Primary outcome measure | 1. HR HPV measured in urine sample at baseline 2. CIN2+ via routine cervical screening obtained from clinical test results The above measures will be used to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the urine HPV test |
| Secondary outcome measures | Current secondary outcome measures as of 11/04/2023: 1. Presence of clinically important HPV infection measured using urine HPV / methylation test at baseline (used to calculate diagnostic test accuracy (sensitivity, specificity, NPV and PPV)) 2. HPV results from urine collected via a plain sterile urine pot and urine collected via Colli-Pee or alternative sampling device at baseline 3. Preference for urine or vaginal sampling compared to routine sampling for cervical screening assessed by participant questionnaire at baseline 4. To measure the concordance of urinary, vaginal and cervical HPV test results _____ Previous secondary outcome measures: 1. Presence of clinically important HPV infection measured using urine HPV / methylation test at baseline (used to calculate diagnostic test accuracy (sensitivity, specificity, NPV and PPV)) 2. HPV results from urine collected via a plain sterile urine pot and urine collected via Colli-Pee or alternative sampling device at baseline 3. Preference for urine compared to routine sampling for cervical screening assessed by participant questionnaire at baseline |
| Overall study start date | 01/09/2020 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 24 Years |
| Upper age limit | 70 Years |
| Sex | Female |
| Target number of participants | 1420 |
| Participant inclusion criteria | Current inclusion criteria as of 18/01/2022: 1. Age 24 -70 years 2. Written, informed consent to participate 3. Attended or attending gynaecology or colposcopy clinic at Manchester University NHS Foundation Trust 4. Undergoing cervical screening, management of abnormal cervical screening or assessment of gynaecological symptoms Previous inclusion criteria as of 28/09/2021: 1. Age 24 -70 years 2. Written, informed consent to participate 3. Attending gynaecology or colposcopy clinic at Manchester University NHS Foundation Trust 4. Undergoing cervical screening, management of abnormal cervical screening or assessment of gynaecological symptoms Previous inclusion criteria: 1. Age 25 - 70 years 2. Written, informed consent to participate 3. Attending gynaecology or colposcopy clinic at Manchester University NHS Foundation Trust 4. Undergoing cervical screening, management of abnormal cervical screening or assessment of gynaecological symptoms |
| Participant exclusion criteria | Current exclusion criteria as of 11/04/2023: 1. Pregnant 2. Previous hysterectomy 3. Unable to produce a urine sample and/or vaginal sample 4. Unable to comprehend the Patient Information Sheet and consent form 5. Any condition that would compromise participant safety or data integrity _____ Previous exclusion criteria: 1. Pregnant 2. Previous hysterectomy 3. Unable to produce a urine sample 4. Unable to comprehend the Patient Information Sheet and consent form 5. Any condition that would compromise participant safety or data integrity |
| Recruitment start date | 22/02/2021 |
| Recruitment end date | 31/12/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Oxford Road
Manchester
M13 9WL
United Kingdom
Sponsor information
University/education
Faculty of Biology, Medicine and Health
Carys Bannister Building
Dover Street
Manchester
M13 9PL
England
United Kingdom
| Phone | +44 (0)161 275 5436 |
|---|---|
| fbmhethics@manchester.ac.uk | |
| Website | http://www.manchester.ac.uk/ |
"ROR" |
https://ror.org/027m9bs27 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high impact peer-reviewed journal. |
| IPD sharing plan | We plan to share anonymised, non editable, participant level data with other researchers upon reasonable request. No identifiable confidential information will be shared. Participants will consent to this via the study consent form. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/01/2025: The overall end date was changed from 30/06/2025 to 31/12/2026.
06/10/2023: The following changes were made:
1. The overall study end date was changed from 01/09/2023 to 30/06/2025.
2. The recruitment end date was changed from 01/09/2023 to 31/12/2024.
3. The intention to publish date was changed from 01/03/2024 to 31/12/2025.
11/04/2023: The following changes have been made:
1. The recruitment end date has been changed from 01/01/2023 to 01/09/2023.
2. The intervention has been changed.
3. The secondary outcome measures have been changed.
4. The participant exclusion criteria have been changed.
5. The plain English summary has been updated to reflect these changes.
18/01/2022: The following changes were made to the trial record:
1. The interventions were changed.
2. The inclusion criteria were changed.
3. The target number of participants was changed from 600 to 1420.
4. The plain English summary was updated to reflect these changes.
28/09/2021: The following changes were made to the trial record:
1. The acronym was added and the scientific title was updated accordingly.
2. The inclusion criteria were updated.
3. The target number of participants was changed from 500 to 600.
16/02/2021: Trial’s existence confirmed by North West Great Manchester West Ethics Committee.
