In 2015, patients, doctors and researchers agreed that improving womb cancer detection in women with abnormal vaginal bleeding was important enough to rank 2nd in a list of 10 top research priorities. Eight years on, clinical practice is still the same, but we have taken big strides towards real change. Our team has been working to address this priority, as well as other areas of unmet need in women’s cancer care, for over 20 years. In 2015, our team leader – Prof Martin Widschwendter – secured funding for a large-scale research project funded by the European Commission and The Eve Appeal. Our initial results were published in 2022 and now, in 2023, we are publishing ‘real-world’ data showing that a new test, called the WID-qEC test, outperforms current methods for womb cancer detection. The new data also highlight some of the problems in the current pathway for detection of womb cancer in women and people with abnormal vaginal bleeding.
What happens when someone has symptoms of womb cancer?
The most common symptom of womb cancer is abnormal bleeding from the vagina, this includes any bleeding after the menopause (three quarters of people with womb cancer are post-menopausal), bleeding between periods, after sex, or heavier periods than are normal for you. 800,000 women get abnormal bleeding investigated every year in the UK. Even though abnormal vaginal bleeding is the most common symptom of womb cancer, less than 1 in 10 of those investigated for this symptom will be diagnosed with womb cancer. The process for getting to a diagnosis of cancer or an ‘all clear’ is complicated, involves many different tests, and can take weeks or months.
Currently, when someone goes to their doctor with symptoms, they will be referred to a specialist gynaecology clinic. Their specialist appointment involves an ultrasound scan at a hospital, usually a transvaginal ultrasound scan, which is used to visualise the inside of the womb and measure the thickness of the womb lining using a scanner probe which is put into the vagina.
When the scan results show there might be a cancer, a surgical diagnostic procedure – a biopsy of the womb lining – is needed. For some women, this can be done at the time of the scan using a gentle straw-like suction device that is put through the cervix into the womb, called a Pipelle®. However, most commonly, women undergo a hysteroscopy, where a telescope is inserted through the vagina, through the cervix and up into the womb to visualise the womb lining and a targeted biopsy can then be taken. A hysteroscopy can be done either at an out-patient appointment or under general anaesthetic. The biopsy is then sent off to pathology, where it is assessed under the microscope to check for signs of cancer.
Data from our study highlights some of the problems with the process
Ultrasound scans require highly trained staff and the use of expensive equipment. Our colleagues at UCLH for example, have specialist expertise and use many different kinds of scanning techniques to measure womb lining. Across the United Kingdom different hospitals have access to differing levels of expertise and resources, which leads to inequities in health around the country.
Measuring the thickness of the womb lining to decide who needs further testing can be challenging, and in many cases the first ultrasound test does not provide a definite result, meaning that women need more than one form of ultrasound, and sometimes also an MRI scan. In our study, called EPISURE, most women needed more than one type of scan: the 399 women had a total of 603 ultrasound or MRI scans, equating to nearly 40% of the patients needing more than one form of imaging to decide their next steps.
Even though transvaginal ultrasound is very effective at detecting womb cancer, for patients with a thickened womb lining it is less effective at telling the difference between cancer and other conditions. This means that many patients without cancer also need a biopsy. In the EPI-SURE study, endometrial thickness measurements from imaging required follow up with a surgical diagnostic procedure in 75 women without cancer. In contrast, only 10 women without cancer had a positive WID-qEC test result that would have required follow up with a surgical diagnostic procedure. The thickness of the womb lining changes naturally during the menstrual cycle, with age and with HRT use; so it’s not possible to have a one-size-fits-all measurement. These issues have led to different hospitals and countries using different thickness measurements as the cut-off for needing further tests in womb cancer detection.
Although some women find hysteroscopy manageable, some do find it painful and distressing. Pipelle® biopsies can be carried out in the outpatient clinic without general anaesthetic, but sometimes cause a degree of pain and anxiety. Additionally, Pipelle® biopsies have a high failure rate: in our study 56 women were deemed eligible for a Pipelle biopsy but 24 of these led to an inconclusive result, meaning that these women had to have a hysteroscopy and biopsy afterwards.
Time to diagnosis is another issue with the current process, it can take weeks or even months before a final diagnosis is reached. This of course causes an extra level of stress on what is already an extremely worrying time for people getting concerning symptoms checked.
All in all, the current diagnostic pathway is very complex, involves a lot of invasive and sometimes painful tests, and can take a long time to reach a diagnosis. A simpler, less invasive, and more objective test is needed.
The new WID-qEC test
The new test, the WID-qEC, is based on simple PCR technology, which is commonly used in the NHS for things like COVID testing, making it simple, fast and affordable. The test works by detecting cancer specific DNA in a cervical screening sample. The test looks for ‘tags’ on top of DNA called DNA methylation. DNA from cancer cells has a particular pattern of DNA methylation, it’s like a unique barcode that can be specifically ‘scanned’ by our WID-qEC test to answer the question as to whether there is a womb cancer or not.
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Over a 6 month period, women aged 45 or older with abnormal vaginal bleeding took part in our study while being investigated at the UCLH gynaecological rapid access clinic, which is a centre of excellence. We compared our WID-qEC test in detecting womb cancer to the current method of transvaginal ultrasound scanning. A cervical sample was taken for the WID-qEC test before the initial ultrasound scan; patients then continued down the current pathway for womb cancer investigation.
The WID-qEC was better than imaging as a test for women with abnormal vaginal bleeding. It picked up the same number of womb cancer cases as ultrasound but could substantially reduce the need for surgical diagnostic procedures to rule out womb cancer. Using the WID-qEC test would save nearly 90% of peri- and post-menopausal women from needing invasive surgical biopsies when getting abnormal vaginal bleeding symptoms checked.
The WID-qEC test is far less invasive than existing methods and getting the cervical sample does not require any specialist equipment and staff. The WID-qEC test could streamline the pathway for the investigation of abnormal vaginal bleeding and reduce the pressures on rapid access gynaecology clinics, and potentially save the NHS money.
Hopes for the future
Our hope for the future is to implement our WID-qEC test into the NHS! We see big potential for the WID-qEC in two main areas:
- As a tool to decide which women with abnormal vaginal bleeding require an urgent
hospital referral, and which women are most likely to have a benign and non-urgent condition and can be observed or treated conservatively. This would substantially reduce the number of urgent hospital visits required and the number of procedures to be undertaken. - As a surveillance tool in women at a higher risk due to a genetic predisposition like Lynch Syndrome or other risk factors including obesity, etc. Currently, most women with Lynch Syndrome undergo annual surveillance of some sort but the procedures vary across the country. Using our test, women could take a vaginal swab sample at home and send it to the lab for testing, thereby reducing the need for a hospital visit.
After all these years of working in cancer research, it feels great to be in a position where we have a test that could easily be implemented into the healthcare system. More importantly, to have a test that could make a big difference and have a positive impact on the lives of women getting checked for a potential womb cancer is amazing!
We would like to thank everyone who has supported over the years and donated to The Eve Appeal. We wouldn’t have this test today without your support. Each and every one of you has played your part in this achievement.
You can find the full research paper in The Lancet Oncology on this link.