ACES primary care: Alternative cervical screening in primary care
| ISRCTN | ISRCTN58683340 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN58683340 |
| EudraCT/CTIS number | Nil Known |
| IRAS number | 309113 |
| Secondary identifying numbers | IRAS 309113, CPMS 51674 |
- Submission date
- 08/03/2022
- Registration date
- 09/03/2022
- Last edited
- 11/04/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
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 by comparing HPV detection rates in urine and cervical samples.
Who can participate?
Women and people with a cervix attending routine cervical screening appointments at participating GP practices or NHS clinics.
What does the study involve?
Individuals will be asked to complete some brief questions about their health and provide a first void urine sample. They will also be asked to complete a short questionnaire to understand views and preferences of current cervical screening attendees. Samples will be tested for high-risk HPV and HPV-positive samples will undergo methylation testing.
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 of taking part.
Where is the study run from?
The University of Manchester (UK)
When is the study starting and how long is it expected to run for?
September 2020 to December 2024
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 | +44 161 701 6941 |
|---|---|
| suzanne.carter@manchester.ac.uk |
Principal Investigator
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 | +44 161 701 6941 |
| emma.crosbie@manchester.ac.uk |
Study information
| Study design | Multicentre observational cross sectional study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | GP practice |
| Study type | Screening |
| Participant information sheet | https://sites.manchester.ac.uk/aces/ |
| Scientific title | Urine HPV testing for cervical screening in primary care |
| Study acronym | ACES Primary Care |
| Study hypothesis | Urine HPV testing is an accurate alternative to routine cervical screening in general screening population |
| Ethics approval(s) | Approved 14/02/2022, South West - Cornwall & Plymouth Research Ethics Committee (Ground Floor, Temple Quay House, 2 The Square, Bristol, BS1 6PN, UK; +44 (0)207 1048071; cornwallandplymouth.rec@hra.nhs.uk), ref 22/SW/0007 |
| Condition | Identification of cervical pre cancer in the general screening population using urine HPV testing |
| Intervention | Current intervention as of 11/04/2023: This study will see if a urine test can accurately identify individuals with cervical pre-cancer and those who continue to be HPV positive after treatment by comparing HPV detection rates in matched urine and cervical samples. Samples will be tested for high-risk HPV. HPV-positive samples will undergo methylation testing. Prior to routine clinical procedures, we will collect a voided urine sample. Urine samples will be self-collected at the GP practice or other NHS clinic, in the privacy of the clinic bathroom. Urine will be collected with a Colli-Pee device, which reliably collects a standardised volume of first void urine. 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. A routine cervical screening (‘Pap’ smear) will then be taken as part of the participant's routine clinical cervical screening care. We will directly compare HPV detection rates, concordance between urine and matched cervical samples and CIN2+ detection rates in urine samples. 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 acceptability questionnaire to gauge their 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. _____ Previous intervention: 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 matched urine and cervical samples. Samples will be tested for high risk HPV. HPV positive samples will undergo methylation testing. Prior to routine clinical procedures, we will collect a voided urine sample. Urine samples will be self collected at the GP practice, in the privacy of the clinic bathroom. Urine will be collected with a Colli-Pee device, which reliably collects a standardised volume of first void urine. 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. A routine cervical screening (‘Pap’ smear) will then be taken as part of the participant's routine clinical cervical screening care. We will directly compare HPV detection rates, concordance between urine and matched cervical samples and CIN2+ detection rates in urine samples. 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 acceptability questionnaire to gauge their 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. |
| Intervention type | Other |
| Primary outcome measure | 1. High risk HPV detection rate in matched urine and cervical samples at baseline 2. CIN2+ detection rates according to routine cervical screening outcomes The above measures will be used to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the urine HPV test for CIN2+ detection compared to routine cervical screening |
| Secondary outcome measures | 1. Concordance of HR-HPV+ test results in matched urine and cervical samples measured as in the primary outcome measure at baseline 2. Presence of CIN2+ measured using urine HPV+ test combined with a methylation+ test at baseline (used to calculate diagnostic test accuracy (sensitivity, specificity, NPV and PPV) 3. Preference for urine compared to routine sampling for cervical screening assessed by participant questionnaire at baseline 4. Reasons for declining to take part in the study assessed by participant questionnaire at the time of declining |
| Overall study start date | 01/09/2020 |
| Overall study end date | 31/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 24 Years |
| Upper age limit | 70 Years |
| Sex | Female |
| Target number of participants | 1,500 - 2,000 |
| Participant inclusion criteria | 1. Age 24-70 years 2. Written, informed consent to participate 3. Undergoing routine NHS cervical screening or management of abnormal cervical screening |
| Participant exclusion criteria | 1. Pregnant 2. Previous hysterectomy 3. Unable to provide a urine sample 4. Unable to understand the Participant Information Sheet and consent form 5. Any condition that would compromise participant safety or data integrity |
| Recruitment start date | 14/03/2022 |
| Recruitment end date | 01/09/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Baguley
Manchester
M23 1JX
United Kingdom
Didsbury
Manchester
M20 6BA
United Kingdom
Victoria Park
Manchester
M14 5BY
United Kingdom
Newall Green
Manchester
M23 2SY
United Kingdom
Manchester
M4 6EE
United Kingdom
Birchfields Road
Fallowfield
Manchester
M14 6FS
United Kingdom
Manchester Royal Infirmary
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 | 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 | 01/09/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in a high impact peer-reviewed journal. |
| IPD sharing plan | At the end of the project we will deposit a fully anonymised dataset in an open data repository where it will be permanently stored. Researchers at other institutions can access the anonymised data directly from the repository and use it for further research or to check our analysis and results The data will be completely anonymised and stored on Figshare (https://figshare.manchester.ac.uk/). Researchers at other institutions can access the anonymised data directly from the repository. We are seeking consent from participants for this. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | 08/08/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
11/04/2023: The following changes have been made:
1. The recruitment end date has been changed from 01/09/2023 to 01/09/2024.
2. The intervention has been changed.
3. Didsbury Medical Centre - Dr Whitaker, Surrey Lodge Practice, The Maples Medical Centre, Ancoats Urban Village Medical Practice, Hawthorn Medical Centre and Central Manchester University Hospitals NHS Foundation Trust have been added to the trial participating centres.
4. The plain English summary has been updated to reflect these changes.
08/08/2022: CRUK link added to Results (plain English).
08/03/2022: Trial's existence confirmed by South West - Cornwall & Plymouth Research Ethics Committee.
