Epidemiology and treatment outcomes of endometrial hyperplasia and cancer: A population-based investigation using routine administrative data
Lead Research Organisation:
Queen's University Belfast
Department Name: Centre for Public Health
Abstract
Endometrial cancer is the most commonly diagnosed gynaecological cancer and is the 4th most common cancer in UK women. Endometrial cancer rates have increased substantially; in the UK over 9,000 cases occur annually and rates have increased by over 50% over the past 20 years. Factors associated with prolonged oestrogen exposure are thought to be driving this including the dramatic increase in obesity rates and shifts in reproductive trends, e.g. delaying childbirth until later in life. There is no routine screening for endometrial cancer but endometrial hyperplasia, a recognised precursor, offers an opportunity for prevention, but little is known about its natural history and associated outcomes. Removal of the uterus (hysterectomy) is the primary treatment for endometrial cancer and some types of endometrial hyperplasia but there is a need to evaluate the long-term benefits and risks of fertility-sparing therapies, considering the alarming increases in endometrial cancer in premenopausal women.
This research will answer three primary research questions:
1. Which women are most at risk of progression from endometrial hyperplasia to cancer?
2. What is the impact of non-surgical, fertility-sparing therapies on future cancer risk and reproductive outcomes in endometrial hyperplasia patients?
3. What are the international trends in surgical and non-surgical treatments of endometrial cancer and how do these impact upon survival outcomes?
A pilot endometrial hyperplasia register, located within the Northern Ireland Cancer Registry (NICR), will be utilised and expanded upon to make it one of the world's largest endometrial hyperplasia registers. The register will be linked to NICR records to determine temporal trends in endometrial hyperplasia incidence and progression to endometrial cancer. Medical note reviews will provide details on patient and clinico-pathological factors while additional novel data linkages to drug dispensing and maternity records in Northern Ireland (NI) will be conducted to evaluate, for the first time, population patterns of low-cost progestogen therapies (delivered orally or, more recently via intrauterine devices) in endometrial hyperplasia patients and their long-term impact on clinical outcomes such as hysterectomy, live births and progression to cancer.
Using population-based linked data sources, accessed from established research links, European trends in the use of surgical and non-surgical treatments for endometrial cancer will be determined for the first time according to geography and healthcare systems. Pooled analyses of large endometrial cancer cohorts from the UK, Belgium and the Netherlands will be conducted to evaluate survival outcomes according to non-surgical, progestogen-based therapies. Future research will explore the development of patient decision aid tools to enable better informed joint treatment decision making. The involvement of patients and clinicians throughout will ensure that the research is clinically relevant.
This research programme will generate robust population-level evidence to inform diagnostic, treatment and surveillance strategies for women with endometrial hyperplasia and endometrial cancer and will ultimately lead to better informed clinical decision-making between women and their health care professionals.
This research will answer three primary research questions:
1. Which women are most at risk of progression from endometrial hyperplasia to cancer?
2. What is the impact of non-surgical, fertility-sparing therapies on future cancer risk and reproductive outcomes in endometrial hyperplasia patients?
3. What are the international trends in surgical and non-surgical treatments of endometrial cancer and how do these impact upon survival outcomes?
A pilot endometrial hyperplasia register, located within the Northern Ireland Cancer Registry (NICR), will be utilised and expanded upon to make it one of the world's largest endometrial hyperplasia registers. The register will be linked to NICR records to determine temporal trends in endometrial hyperplasia incidence and progression to endometrial cancer. Medical note reviews will provide details on patient and clinico-pathological factors while additional novel data linkages to drug dispensing and maternity records in Northern Ireland (NI) will be conducted to evaluate, for the first time, population patterns of low-cost progestogen therapies (delivered orally or, more recently via intrauterine devices) in endometrial hyperplasia patients and their long-term impact on clinical outcomes such as hysterectomy, live births and progression to cancer.
Using population-based linked data sources, accessed from established research links, European trends in the use of surgical and non-surgical treatments for endometrial cancer will be determined for the first time according to geography and healthcare systems. Pooled analyses of large endometrial cancer cohorts from the UK, Belgium and the Netherlands will be conducted to evaluate survival outcomes according to non-surgical, progestogen-based therapies. Future research will explore the development of patient decision aid tools to enable better informed joint treatment decision making. The involvement of patients and clinicians throughout will ensure that the research is clinically relevant.
This research programme will generate robust population-level evidence to inform diagnostic, treatment and surveillance strategies for women with endometrial hyperplasia and endometrial cancer and will ultimately lead to better informed clinical decision-making between women and their health care professionals.
Planned Impact
The primary beneficiaries of this research include women diagnosed with endometrial cancer (or its precursor endometrial hyperplasia), clinicians, policy makers and healthcare providers.
Improved policy making:
In the short to medium-term, targeted dissemination of research findings to national and international clinical policymakers will be undertaken. By exploiting novel population-wide record linkages, this research will ascertain optimal surveillance and treatment strategies to enable the identification of women most at risk of malignant progression to endometrial cancer, where surveillance and treatment strategies can be better targeted. Evidence from population-representative studies are essential to inform clinical management guidelines so that women and their clinicians can make more tailored decisions regarding the risk-benefit profile of current surveillance and treatments options. The inclusion of European data sources means that the findings from research will likely inform international practice, as well as that within the UK.
Improved health systems:
The research findings will provide national healthcare providers with novel information on UK temporal trends in endometrial hyperplasia incidence on a population-level. This will allow for better informed medium to long-term planning of gynaecological health service needs in the UK (e.g. information systems, workforce, service delivery, technologies), therefore improving allocation of scare resources. The identification of women at low risk of progressing from endometrial hyperplasia to endometrial cancer will likely lead to a reduction in the number of hysterectomies performed in the UK and hence reduced morbidity and associated healthcare costs. In the longer-term, exploration of the development of decision support aids may result in improved communication between healthcare professionals and women with endometrial hyperplasia or cancer, as well as increased quality and efficiency of joint clinical decision making. Future economic beneficiaries will include potential commercial partners, for the development of (digital) treatment decision aids, which will be informed by the findings from the research programme.
Improved knowledge base:
Using secondary data sources, this research programme will generate population-representative evidence for the clinical management of common gynaecological conditions (endometrial cancer and its precursor condition endometrial hyperplasia) which will enable affected women and their health professionals to make better informed decisions regarding their care. For example, the Northern Ireland Hyperplasia Register will be expanded upon to become one of the largest registers of its kind in the world (first in UK) and will provide a unique resource to study the natural history and outcomes from this common condition. Regular stakeholder engagement throughout will ensure that knowledge is exchanged between relevant groups, e.g. patients, clinicians, policy makers, and will ensure that progress is monitored and evaluated throughout. Through our dissemination strategy, the wider UK female population will also benefit from this research through communication and engagement surrounding gynaecological cancer symptom awareness.
Improved capacity to produce and utilise research based on routine health records in order to improve of population health:
This research will increase capacity, in the short, medium and long-term, for population research in the UK that exploits routine health administrative data sources and will provide reliable resources (e.g. databases, IT, human resources) to develop and implement future research. Our dissemination and social media strategy will widely communicate the availability of resources within this fellowship. Moreover, my programme of research will especially raise the profile of gynaecological cancer research (and skills development) within the UK and further afield.
Improved policy making:
In the short to medium-term, targeted dissemination of research findings to national and international clinical policymakers will be undertaken. By exploiting novel population-wide record linkages, this research will ascertain optimal surveillance and treatment strategies to enable the identification of women most at risk of malignant progression to endometrial cancer, where surveillance and treatment strategies can be better targeted. Evidence from population-representative studies are essential to inform clinical management guidelines so that women and their clinicians can make more tailored decisions regarding the risk-benefit profile of current surveillance and treatments options. The inclusion of European data sources means that the findings from research will likely inform international practice, as well as that within the UK.
Improved health systems:
The research findings will provide national healthcare providers with novel information on UK temporal trends in endometrial hyperplasia incidence on a population-level. This will allow for better informed medium to long-term planning of gynaecological health service needs in the UK (e.g. information systems, workforce, service delivery, technologies), therefore improving allocation of scare resources. The identification of women at low risk of progressing from endometrial hyperplasia to endometrial cancer will likely lead to a reduction in the number of hysterectomies performed in the UK and hence reduced morbidity and associated healthcare costs. In the longer-term, exploration of the development of decision support aids may result in improved communication between healthcare professionals and women with endometrial hyperplasia or cancer, as well as increased quality and efficiency of joint clinical decision making. Future economic beneficiaries will include potential commercial partners, for the development of (digital) treatment decision aids, which will be informed by the findings from the research programme.
Improved knowledge base:
Using secondary data sources, this research programme will generate population-representative evidence for the clinical management of common gynaecological conditions (endometrial cancer and its precursor condition endometrial hyperplasia) which will enable affected women and their health professionals to make better informed decisions regarding their care. For example, the Northern Ireland Hyperplasia Register will be expanded upon to become one of the largest registers of its kind in the world (first in UK) and will provide a unique resource to study the natural history and outcomes from this common condition. Regular stakeholder engagement throughout will ensure that knowledge is exchanged between relevant groups, e.g. patients, clinicians, policy makers, and will ensure that progress is monitored and evaluated throughout. Through our dissemination strategy, the wider UK female population will also benefit from this research through communication and engagement surrounding gynaecological cancer symptom awareness.
Improved capacity to produce and utilise research based on routine health records in order to improve of population health:
This research will increase capacity, in the short, medium and long-term, for population research in the UK that exploits routine health administrative data sources and will provide reliable resources (e.g. databases, IT, human resources) to develop and implement future research. Our dissemination and social media strategy will widely communicate the availability of resources within this fellowship. Moreover, my programme of research will especially raise the profile of gynaecological cancer research (and skills development) within the UK and further afield.
Publications
Butler E
(2022)
Testosterone therapy and cancer risks among men in the SEER-Medicare linked database
in British Journal of Cancer
Cardwell CR
(2021)
Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study.
in Prostate cancer and prostatic diseases
Cardwell CR
(2020)
The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.
in Epidemiology (Cambridge, Mass.)
Houston MG
(2023)
Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.
in British journal of clinical pharmacology
Jordao H
(2023)
Pre-eclampsia during pregnancy and risk of endometrial cancer: a systematic review and meta-analysis
in BMC Women's Health
Liu P
(2020)
Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.
in British journal of cancer
McMenamin ÚC
(2021)
Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank.
in The American journal of gastroenterology
Description | Citation in clinical review article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://onlinelibrary.wiley.com/doi/full/10.1002/jhbp.1001?casa_token=Qih2flgBKvgAAAAA%3AtexAXMU-aWy... |
Description | Citation in clinical review article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994523/ |
Description | Citation in clinical review article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://www.sciencedirect.com/science/article/pii/S1499267120303762?casa_token=MgHSb1IqJl4AAAAA:ZRIv... |
Description | Citation in clinical review article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://ascopubs.org/doi/full/10.1200/JCO.22.00883?role=tab |
Description | Citation in clinical review article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://www.frontiersin.org/articles/10.3389/fonc.2021.627270/full |
Description | Citation in clinical review article |
Geographic Reach | North America |
Policy Influence Type | Influenced training of practitioners or researchers |
URL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936160/ |
Description | Citation in clinical review articles |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://aacrjournals.org/cebp/article-abstract/30/7/1302/670999/Sex-Hormone-and-Colorectal-Cancer-Th... |
Description | Citation in in global clinical information website 'UpToDate' |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://www.uptodate.com/contents/epidemiology-pathogenesis-and-classification-of-cholangiocarcinoma |
Description | Editorial article |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
URL | https://www.nature.com/articles/s41391-021-00383-8 |
Description | Northern Ireland Department for the Economy PhD studentship |
Amount | £49,000 (GBP) |
Organisation | Department for the Economy, Northern Ireland |
Sector | Public |
Country | United Kingdom |
Start | 09/2019 |
End | 09/2021 |
Description | Northern Ireland Department for the Economy PhD studentship |
Amount | £49,000 (GBP) |
Organisation | Department for the Economy, Northern Ireland |
Sector | Public |
Country | United Kingdom |
Start | 09/2021 |
End | 09/2023 |
Description | Scientific Member of UK Audit & Research Collaborative n Obstetrics and Gynaecology (UKARCOG) |
Organisation | UKARCOG |
Sector | Academic/University |
PI Contribution | I became a Scientific Member of UK Audit & Research Collaborative in Obstetrics and Gynaecology (UKARCOG), which is a network of trainee / junior doctors that work jointly on large audit and research projects in the field of obstetrics and gynaecology (O&G) throughout the UK. I have provided regular reviews of applications to the network for support for research projects and audits from trainee medical doctors. My input is particularly focused on the research design and data analysis perspective. |
Collaborator Contribution | The UK Audit & Research Collaborative in Obstetrics and Gynaecology (UKARCOG), which is a network of trainee / junior doctors that work jointly on large audit and research projects in the field of obstetrics and gynaecology (O&G) throughout the UK. The overall objectives of the network are: - Engage the network of UK trainees to undertake audit and research projects. - Improve healthcare service locally and nationally. - Perform joint nationwide audit and research projects. - Support the aspirations, in concert with the RCOG (Royal College of Obstetricians and Gynaecologists), of doctors training in O&G in order to benefit our patients. Through the completion and publication of our audit and research projects, the aim is to improve medical practice and thus the quality of women's health care. |
Impact | No outputs from my participation yet. |
Start Year | 2021 |
Description | 'Tips from the Experts' Fellowship Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Invited panel member for Queen's University Belfast 'Tips from the experts' Fellowship workshop. Between 50-100 PhD and Postdoctoral researchers researchers attended and there were questions and discussion around the application process for fellowships and what makes a strong application. Evaluations reported increased knowledge amongst participants of the process of applying to UK and internationally-funded Fellowships. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.qub.ac.uk/Research/Support-for-researchers/Funding-information/UK-international-funding/... |
Description | Established an Endometrial Hyperplasia Patient & Public Involvement Group |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Established an Endometrial Hyperplasia Patient & Public Involvement Group to share my research aims and plans with relevant end-users. This was a valuable opportunity to obtain the views and perspectives of patients who have personal lived experience of the disease/condition under study and ensures that the research is relevant to patients and their needs. |
Year(s) Of Engagement Activity | 2021,2022 |
Description | Invited commentary on medical information website |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Based on my expertise in cancer pharmacoepidemiology, I was invited to provide a brief commentary on a published article The article investigated the association between aspirin use and survival in lung cancer patients and I provided a critical appraisal of the methodology used to enhance readers understading of the strengths and limitations of the study. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.medscape.com/viewarticle/963904 |
Description | Invited commentary on medical information website 'Medscape' |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Provided and invited comment on published pharmacoepidemiology research article for 'Medscape', an international website providing access to medical information and training for clinicians Medscape is the leading online global destination for physicians and healthcare professionals worldwide, offering the latest medical news and expert perspectives; essential point-of-care drug and disease information; and relevant professional education and CME. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.medscape.com/viewarticle/963904 |
Description | Invited talk at the Northern Ireland Gynaecological Oncology Annual meeting 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Delivered an invited presentation to the Northern Ireland Gynaecological Oncology Annual meeting where I communicated my research plans on endometrial cancer to all gynaecological oncologists/surgeons in Northern Ireland (Antrim, October 2019). The talk sparked questions and discussion and the audience expressed increased interest in my research. |
Year(s) Of Engagement Activity | 2019 |
Description | Invited talk to cancer patients and carers within the Northern Ireland Cancer Research Consumer Forum |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Invited presentation at a meeting of the Northern Ireland Cancer Research Consumer Forum, which is composed of a group of patients and carers affected by cancer who have an interest in shaping and supporting cancer research (November 2019). Questions and discussion was sparked afterwards and the audience reported increased interest and understanding of my research into endometrial cancer. |
Year(s) Of Engagement Activity | 2019 |
URL | http://engage.hscni.net/what-is-ppi/testimonials/involvement-in-practice-case-studies/ni-cancer-rese... |
Description | Invited to talk at QUB School of Nursing and Midwifery Away Day (funding discussion panel) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Invited panel member for Queen's University Belfast School of Nursing & Midwifery Away Day Funding and Fellowships workshop. Between 50-100 PhD, Postdoctoral researchers and academic staff attended and there were questions and discussion around the application process for fellowships and what makes a strong application. Evaluations reported increased knowledge amongst participants of the process of applying to UKRI-funded Fellowships. |
Year(s) Of Engagement Activity | 2021 |
Description | Organiser of Women's Early Career Academic Network (WeCAN) Gender Equality seminars |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I lead the organisation of quarterly seminars as part of the Women's Early Career Academic Network (WeCAN). WeCAN is one of the Queen's University Belfast School of Medicine, Dentistry and Medical Sciences Gender Equality Committee initiatives (the School holds an Athena SWAN Gold award). The aim of WeCAN is to provide early career researchers and academics (particularly females) with support and guidance, create awareness of and provide opportunities to discuss issues that affect women's academic career development and success, and provide opportunities to share strategies for dealing with academic life and work-life balance. Guest speakers for the series of WeCAN events discuss their career and career pathways, challenges and opportunities encountered, how they balance the demands of the clinical and academic workloads and work-life-balance. More recent topics have included the impact of the Covid-19 pandemic, the intersection of race and gender in academia and transgender awareness. |
Year(s) Of Engagement Activity | 2020,2021,2022 |
URL | https://www.qub.ac.uk/schools/mdbs/Connect/GenderEqualityOffice/NewsandEvents/SMDBSWomensEarlyCareer... |
Description | Presentation to BSc (Hons) Biomedical Science students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Undergraduate students |
Results and Impact | Presentation to all final year BSc (Hons) Biomedical Science students at Queen's University Belfast on the topic of my ongoing research and wider public health research in the institution, as well as an outline of my career pathway to date. The talk sparked questions and discussion afterwards, and the students reported increased interest in the subject area and enquired about potential PhD opportunities in my research centre. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.qub.ac.uk/courses/undergraduate/biomedical-science-bsc-b940/ |
Description | Presentation to the Northern Ireland Cancer Registry Council |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | I presented my research on the premalignant condition endometrial hyoerplasia to stakeholders who are part of the Northern Ireland Cancer Registry Council, which includes clinicians (e.g., oncologists), cancer charity representatives, public health policy-makers, cancer patients and carers as well as staff within the Cancer Registry. The Postdoctoral researcher working on the project also presented to the group The prrsentation sparked questions and discussion afterwards, and the participants reported increased interest in the subject area. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.qub.ac.uk/research-centres/nicr/ |
Description | Scientific Member of UK Audit & Research Collaborative (UKARCOG) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I became a Scientific Member of UK Audit & Research Collaborative (UKARCOG), which is a network of trainee / junior doctors that work jointly on large audit and research projects in the field of obstetrics and gynaecology (O&G) throughout the UK. |
Year(s) Of Engagement Activity | 2021,2022 |
URL | http://ukarcog.org/ |