Testing for levels of CA125 in the blood is a useful tool for gauging the likelihood of ovarian cancer and could help detect other types of cancer among patients in primary care, according to research presented at the 2019 NCRI Cancer Conference.
Although the CA125 test is already in use in countires around the world, this is the first large study to look at how well it performs in general practice for testing women who have possible symptoms of ovarian cancer.
Researchers say their results could guide women and their GPs on whether more invasive tests are needed to check for ovarian and other cancers. They also say that clinical guidelines could now be improved to ensure urgent referrals are made for women most at risk.
The research was led by Dr Garth Funston, a Clinical Research Fellow at the University of Cambridge, UK. He said: “Less than half of women with ovarian cancer survive for five years following diagnosis. The majority of women are not diagnosed until the disease is advanced, which makes it more difficult to cure.
“It’s important that GPs have effective tools to detect ovarian cancer early and ensure patients are referred appropriately. While CA125 is widely used in general practice in the UK and internationally, prior to this study, it was unclear how effective a test it really was in general practice.”
The research included data on 50,780 women who visited GPs in England with possible signs of ovarian cancer, such as persistent bloating or abdominal pain, and were tested for levels of CA125 in their blood between May 2011 and December 2014.
Researchers compared the results of these blood tests with data on which women were diagnosed with ovarian cancer or another form of cancer in the 12 months following their blood test.
They discovered that 10% of women who had an abnormally high level of CA125 in their blood were found to have ovarian cancer. This figure is much higher than previously thought and ten times higher than the estimate given in the UK’s 2011 NICE (National Institute for Health and Care Excellence) guidelines on ovarian cancer diagnosis.
In women who had abnormal test results and were aged 50 years or older, 15% were found to have ovarian cancer, while in women under 50 with high CA125 levels, only 3% were diagnosed with ovarian cancer.
Results also showed that around 17% of women 50 years or older with an abnormal result were diagnosed with another form of the disease, such as pancreatic, lung or womb cancer.
The large size of the study meant that researchers were, for the first time, able to look in detail at women with different levels of CA125 in their blood in general practice and give more accurate estimates of cancer risk according to those levels.
The amount of CA125 in the blood is measured in units per millilitre (U/ml) and it can range from one to thousands. Dr Funston and his colleagues found, for example, that women with a CA125 level of 51 U/ml had a 3% probability of ovarian cancer. Three per cent is the level of risk at which NICE recommends urgent cancer referral.
Dr Funston said: “Our work shows that CA125 is a very useful test for detecting ovarian cancer in general practice.
“Our results can be used by doctors to determine the chance of a woman in general practice having ovarian cancer based on the CA125 level. This could help guide decisions made by GPs and their patients about the need for further investigation or referral.
“Our findings also highlight that women with symptoms who are aged 50 years or more and have abnormaly high CA125 levels frequently have other types of cancer. It is really important that GPs are aware of this to ensure these cancers are not missed.”
Dr Funston and his team continue their work on early diagnosis of ovarian cancer. Their study of CA125 blood testing forms part of efforts to create a prediction tool to help GPs spot women who may have the disease as early as possible.
Dr Shibani Nicum, Chair of NCRI’s ovarian cancer subgroup and consultant medical oncologist at Oxford University Hospitals, who was not involved in the research said: “Diagnosing more cases of ovarian cancer at an early stage could have a big impact on survival and GPs are an essential part of that process.
“These findings could help doctors interpret test results and inform their decisions about which tests their patients need next. For instance, an older woman who has abnormal CA125 level should be considered high risk for ovarian cancer. Even if she does not turn out to have ovarian cancer, she might have another form of the disease and either way she will probably need an urgent referral.
“These finding can also be used to expand on existing clinical guidelines, both in the UK and other countries, to improve ovarian cancer diagnosis at the national and international level.”
Researchers have developed a non-invasive test to detect cervical pre-cancer by analysing urine and vaginal samples collected by the women themselves.
In a presentation at the 2019 NCRI Cancer Conference today (Monday), Dr Belinda Nedjai said that the self-sampling test had proved popular with women taking part in the study and this meant that it was likely to improve participation in cervical cancer screening programmes.
“The initial use of self-sampling is likely to be for women who do not attend clinic after a screening invitation and in countries without a cervical cancer screening programme. In the longer term, self-sampling could become the standard method for all screening tests. The study indicated that women much preferred doing a test at home than attending a doctor’s surgery,” said Dr Nedjai, who is Senior Research Fellow and Director of the Molecular Epidemiology Lab at Queen Mary University of London, UK.
“To the best of our knowledge, this study is the largest to test a methylation classifier, called S5, in urine and self-collected cervical samples to detect pre-cancer lesions in women who have been referred for further investigation. We expect the self-sampling test to improve acceptance rates for cervical cancer screening, as well as reducing costs to health services and improving the performance of screening programmes.”
The current gold-standard pap smear test is taken in the clinic and often follows a positive test for the human papilloma virus (HPV).
Dr Nedjai said: “HPV testing is rapidly becoming the primary screening method for cervical cancer worldwide. It is a very sensitive method, very good at detecting true positives, but lacks specificity – in other words, a second test is needed to exclude HPV positive women that are not at increased risk of developing cancer. The choice of an appropriate strategy for high-risk HPV positive women is a key issue.”
The S5 test developed by Dr Nedjai and her colleagues at Queen Mary, measures DNA methylation – a chemical change to one of the four DNA base letters that make up the human genetic code. S5 looks at DNA methylation of four HPV types most strongly associated with cancer – HPV16, HPV18, HPV31 and HPV33 – and the human gene EPB41L3 to produce a score that indicates the level of risk. If the score is above a selected cut-off it indicates an increased risk of a pre-cancer lesion, and the higher the score the higher the risk of cancer. They had discovered in earlier research that when S5 was used on cervical samples collected by health care professionals, it was 100% accurate at detecting invasive cervical cancer, and 93% accurate at detecting pre-cancer in women who had an HPV positive test.
Cervical cancer is preceded by the abnormal growth of precursor cells on the surface of the cervix – so called cervical intraepithelial neoplasia (CIN) or pre-cancer – that can develop into cervical cancer. It is divided into three stages (CIN1, CIN2 and CIN3), with the likelihood of the cells developing into cancer increasing at each stage.
“We decided to assess whether S5 could identify women who had CIN3 pre-cancer lesions using urine and vaginal samples,” said Dr Nedjai.
Women attending the colposcopy clinic at the Royal London Hospital as a consequence of an abnormal smear test or positive HPV result were asked to take part in a study led by Professor Jack Cuzick, Director of the Wolfson Institute of Preventive Medicine at Queen Mary. A total of 620 women provided vaginal samples, collected themselves using vaginal swabs, and 503 of these women also provided a urine sample. The researchers extracted and analysed the DNA in the lab and generated S5 scores.
“We found that the S5 classifier with or without HPV testing worked well in both urine and vaginal samples,” said Dr Nedjai. “It distinguished between women who had no pre-cancerous lesions and those who had CIN3 or higher lesions.
“We evaluated two distinct ways that S5 could be used. We first tested S5 as a secondary test on HPV positive women to limit the number of patients sent to colposcopy. In urine, S5 was better at correctly identifying women who did have pre-cancer lesions than testing for the presence of HPV16 or 18; 96% of true CIN3 were identified with S5 compared to 73% with an HPV16 or 18 test.
“Secondly, we evaluated S5 as a standalone test, without first doing HPV testing. We adjusted the cut-offs to identify at least 85% of true positives. Urine performed as well as self-collected vaginal samples.
“We are currently working on new markers to try to improve the accuracy of the classifier even further, but these findings represent an advance in cervical cancer screening, especially for women who do not attend the clinic, such as older women, or women who find the smear test too painful or who do not have access to a screening programme in their country. We think it’s promising.”
In the future, Dr Nedjai said the samples could be collected at home for both HPV and S5 methylation analysis without the need to go to the clinic.
Dr Manuel Rodriguez-Justo is a consultant pathologist at University College London (UK) and a member of the NCRI’s sub-committee on early detection and prevention. He was not involved with the research. He commented: “This is exciting research that shows it’s possible to detect cervical pre-cancer that is at high risk of developing into invasive cancer in urine and vaginal samples collected by women in the comfort and privacy of their own homes. This has the potential to revolutionise the way a positive HPV test is followed up, as well as making it easier for women in countries with no cervical cancer screening programme to be tested.
“The cervical screening programme in the UK has been very successful but there has been also a decline in its uptake, particularly in some areas in the UK and specific ethnic groups. If the results of this study are validated by other groups, the implementation of urine-based testing and self-sampled vaginal samples will, potentially, increase uptake and reduce costs for the screening programmes whilst achieving high sensitivity to detect pre-malignant lesions.”
Cervical cancer is the fourth most frequently occurring cancer in women in the world. In 2018, there were an estimated 570,000 new cases of cervical cancer and 310,000 women died from the disease. Infection with HPV is the main cause of cervical cancer. More than 25 different types of HPV are transmitted through sexual contact and 12 of them carry a high risk of triggering the development of cancer cells by inactivating tumour suppressor proteins (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 68).
Chemical analysis of blood samples, combined with an artificial intelligence program, could speed up the diagnosis of brain tumours, according to research presented at the 2019 NCRI Cancer Conference.
Brain tumours tend to have ambiguous symptoms, such as headache or memory problems, and a brain scan is currently the only reliable way of diagnosing them.
Researchers say their test, which works by detecting chemical clues shed by brain tumours into the blood, could help improve brain tumour survival by making diagnosis quicker and more efficient.
Dr Paul Brennan, senior clinical lecturer and honorary consultant neurosurgeon at the University of Edinburgh, UK, said: “Brain tumours reduce life expectancy by an average of 20 years. That’s the highest of any cancer.
“We know that 62% of patients are diagnosed in the emergency department, even though they may have seen their GP several times beforehand. This is because diagnosing brain tumours is so difficult. A headache could be a sign of a brain tumour, but it is more likely to be something else and it’s not practical to send lots of people for a brain scan, just in case it’s a tumour. The challenge is identifying who to prioritise for an urgent scan.”
Dr Brennan has worked with Dr Matthew Baker, reader in chemistry at the University of Strathclyde, UK, and chief scientific officer at ClinSpec Diagnostics Ltd to develop a test to help doctors to quickly and efficiently find those patients who are most likely to have a brain tumour.
The test relies on an existing technique, called infrared spectroscopy, to examine the chemical makeup of a person’s blood, combined with an AI program that can spot the chemical clues that indicates the likelihood of a brain tumour.
The researchers tried out the new test on blood samples taken from 400 patients with possible signs of brain tumour who had been referred for a brain scan at the Western General Hospital in Edinburgh, UK. Of these, 40 were subsequently found to have a brain tumour.
Using the test, the researchers were able to correctly identify 82% of brain tumours. The test was also able to correctly identify 84% of people who did not have brain tumours, meaning it had a low rate of ‘false positives.
In the case of the most common form of brain tumour, called glioma, the test was 92% accurate at picking up which people had tumours.
Dr Baker said: “These results are extremely promising because they suggest that our technique can accurately spot who is most likely to have a brain tumour and who probably does not.
“Because the technique requires just a small blood sample, if offers the potential to test a large number of people with suspicious symptoms and give the best indication of who needs an urgent brain scan. This could ultimately speed up diagnosis, reduce the anxiety of waiting for tests and get patients treated as quickly as possible.”
The next step will be to try out the test with 600 more patients who have either been referred for a brain scan via their GP or the hospital emergerncy department. The reserachers say a much smaller proportion of these patients will be subsequently diagnosed with a tumour.
The researchers also say the same technique has the potential to be adapted to other types of cancer that are difficult to diagnose, such as ovarian, pancreatic, bowel and prostate cancer.
Dr Sarah Jefferies, is a member of the NCRI’s glioma subgroup and Clinical Director for Cancer at Addenbrooke’s Hospital, Cambridge, UK and was not involved in the research. She said: “The number of people being diagnosed and dying from brain tumours is increasing and we urgently need better ways to spot and treat the disease.
“This type of testing offers a number of potential advantages. It’s relatively straight-forward for the patient, who need only have a blood test. For the health service, it could combine with clinical assessment to make the process of referring patients for brain scans more efficient.
“We look forward to further assessment of this technique.”
A condition that can progress to myeloma could be identified in patients by their unusually frequent hospital visits, according to research presented at the 2019 NCRI Cancer Conference.
The study found that people with a pre-cancerous blood condition called monoclonal gammopathy of undetermined significance (MGUS) made around twice as many visits to hospital as other people of the same age.
Although myeloma is almost always preceded by MGUS, MGUS is rarely spotted. So, the researchers say this finding could help ensure myeloma is diagnosed at the earliest possible opportunity when the likelihood of successful treatment is highest.
The study was led by Dr Maxine Lamb, a research fellow in the department of health sciences at the University of York, UK. She said: “MGUS is a benign condition that doesn’t have obvious symptoms. It is usually only diagnosed incidentally when doctors are investigating other problems, so around 90% of cases remain undiagnosed.
“In the majority of people, this condition doesn’t progress to cancer. However, virtually all people with myeloma, as well as a proportion of patients with some types of lymphoma, had MGUS before their cancer developed. That’s why we’re interested in spotting this condition.”
Previous research suggests that people with MGUS are also at risk of being diagnosed with autoimmune disorders, fractures and infections. So, Dr Lamb and her team wanted to see if it would be possible to spot MGUS cases based on how often people visited clinics and hospitals for these seemingly unrelated issues.
The study included 2,219 cases (people who were known to have MGUS) as well as 22,190 matched controls (people who had not been diagnosed with MGUS but were similar in terms of their ages, sex and where they live).
Researchers looked at data on out-patient hospital visits both before and after MGUS diagnosis and compared this with hospital visits made by the control group. They calculated rates of hospital attendances per 100 people per month.
On average, they found that MGUS patients had 31 visits per hundred people per month in the three years prior to diagnosis. Among people not diagnosed with MGUS, this figure was 16, meaning that, on average, MGUS patients were 1.9 times as likely to have an outpatient appointment than people without MGUS.
There were even stronger patterns in certain medical specialties. For example, MGUS patients were 5.5 times more likely to visit a nephrology clinic, 3.7 times more likely to visit rheumatology and 2.4 times as likely to visit dermatology. These differences increased in the years after patients were diagnosed with MGUS.
Researchers also looked at a different blood condition, called monoclonal B-cell lymphocytosis, that can lead to other types of blood cancer and they did not see this distinctive pattern of hospital visits, suggesting it may be unique to MGUS.
Dr Lamb said: “Once someone is diagnosed with MGUS they are monitored for signs that that they are developing myeloma. Previous research suggests that myeloma patients whose MGUS had been diagnosed have better survival and we know that, in general, early diagnosis improves cancer survival chances.
“This study suggests a possible way to spot more cases of MGUS and this could give us the opportunity to try to diagnose more cases of myeloma, and some types of lymphoma, at an earlier stage.”
Dr Lamb and her team continue to study MGUS, including how the condition progresses into myeloma and other cancers.
Gordon Cook, Professor of Haematology & Myeloma Studies and Honorary Consultant Haematologist at the University of Leeds, is Chair of the NCRI Myeloma sub-group and was not involved in the research. He said: “Although survival rates for myeloma are improving, we are still diagnosing too many patients late. Approximately one in three cases are diagnosed through an emergency admission. So, improving the diagnostic rate is an unmet need.
“We believe that all cases of myeloma are preceded by MGUS but very few MGUS patients develop myeloma. Spotting MGUS early and finding those at greatest risk of developing myeloma is essential if we are to improve outcomes.
“However, it’s important to remember that MGUS itself does not require treatment and the majority of people found to have MGUS will not go on to develop myeloma.”
People who have a certain type of bacteria in their guts may be at greater risk of developing bowel cancer.
In the first study to use a technique called Mendelian randomisation to investigate the causal role played by bacteria in the development of bowel cancer, Dr Kaitlin Wade, from the University of Bristol (UK), told the 2019 NCRI Cancer Conference today (Monday): “We found evidence that the presence of an unclassified type of bacteria from a bacterial group called Bacteroidales increased the risk of bowel cancer by between 2-15%.
“This means that, on average, people with this type of bacteria within their gut may have a slightly higher risk of bowel cancer compared to those who don’t. We were able to use Mendelian randomisation to understand the causal role that these bacteria may have on the disease. Our findings support previous studies that have shown that Bacteroidales bacteria are more likely to be present, and in larger quantities, in individuals with bowel cancer compared to those without the disease.”
The microbiome is a community of microorganisms, bacteria in this case, that occur naturally in the body. There is increasing evidence that the make-up of the microbiome plays a role in the human health and the body’s susceptibility to disease. The human gut microbiome, which contains approximately three trillion bacteria, aids digestion and provides protection against infections. It is determined by a person’s individual genetic makeup and their environment, so is unique to each person. It also remains relatively stable across a person’s life, unless it is affected by antibiotics, an illness or a change of diet, among other things.
Dr Wade, who is an early career researcher, said: “I was interested to see whether variation in the human gut microbiome, like the number of bacteria or simply the numbers of different types of bacteria, can have an impact on bowel cancer. Lots of studies in mice and humans have shown an association between the gut microbiome and bowel cancer but very few have provided convincing evidence for causality. In other words, it’s really difficult to discern whether components of the gut microbiome can cause bowel cancer, whether the disease itself leads to variation in the gut microbiome or whether the association is due to some other factors that cause variation in both.”
Mendelian randomisation uses complex statistical analysis of data from large populations to provide evidence for cause and effect, rather than just the existence of an association.
“With Mendelian randomisation, we use people’s natural, randomly inherited genetic variations, which alter levels of bacteria within the gut microbiome in a way that mimics a randomised trial, to see whether people with a different genetic makeup, and therefore different gut microbiome profiles, have a different risk of colorectal cancer,” explained Dr Wade. “In this way, we don’t have to edit anyone’s gut microbiome directly by giving antibiotics or probiotics in a randomised trial or waste time waiting to see whether people within the population get colorectal cancer. We just need studies that have already got this information measured.”
The researchers used data from 3,890 people taking part in the Flemish Gut Flora Project, the German Food Chain Plus study and the PopGen study, and 120,328 people in the international Genetics and Epidemiology of Colorectal Cancer Consortium. These studies searched for small variations in the genomes of participants that occur more frequently in people with a particular disease or characteristic than in people without that disease or characteristic – known as genome-wide association studies (GWAS).
They found that genetic variation in the population in particular parts of the genome were linked to the presence or varying amounts of 13 types of gut bacteria, and that people with an unclassified type of bacteria from the Bacteroidales group had a higher risk of bowel cancer compared to people who did not have these bacteria.
Dr Wade said that her findings need to be replicated by other studies using different sets of data and methods before the implications for human health could be fully understood.
“We need to classify the exact species or strain of bacteria in the Bacteroidales group, and we need to do more work to understand how and why human genetic variation can alter the gut microbiome. Even if these results show that these bacteria may cause bowel cancer, we don’t know whether trying to alter them in an effort to reduce the risk of bowel cancer might have other, unforeseen effects on other aspects of health. However, I believe that we are at the forefront of understanding and appreciating the complexity of these relationships – not only those between the human gut microbiome and disease but also between human genetic variation and the gut microbiome itself – which is required to appropriately use these methods to appraise causality,” she concluded.
Professor Ian Tomlinson, incoming Director of the Cancer Research UK Edinburgh Centre, University of Edinburgh, UK, is a member of the NCRI conference scientific committee and was not involved in the study. He said: “Mendelian randomisation methods are increasingly being used routinely to provide indications of causal risk factors by analysing genetic associations with a disease and with risk factors. This is the one of the first studies to use the methods to provide insights into the reasons for the postulated and plausible – but largely unproven – links between the microbiome and bowel cancer.
“The stability of the gut microbiome is in question and there are complex relationships between the types and numbers of bacteria present, and it is therefore too early to ascribe causality to the findings reported. Nevertheless, similar larger studies have the potential for greatly improving our understanding of how bowel cancer develops.”
Breast cancer could be detected up to five years before there are any clinical signs of it, using a blood test that identifies the body’s immune response to substances produced by tumour cells, according to new research presented at the 2019 NCRI Cancer Conference today (Sunday).
Cancer cells produce proteins called antigens that trigger the body to make antibodies against them – autoantibodies. Researchers at the University of Nottingham (UK) have found that these tumour-associated antigens (TAAs) are good indicators of cancer, and now they have developed panels of TAAs that are known already to be associated with breast cancer to detect whether or not there are autoantibodies against them in blood samples taken from patients.
In a pilot study the researchers, who are part of the Centre of Excellence for Autoimmunity in Cancer (CEAC) group at the School of Medicine, University of Nottingham, took blood samples from 90 breast cancer patients at the time they were diagnosed with breast cancer and matched them with samples taken from 90 patients without breast cancer (the control group).
They used screening technology (protein microarray) that allowed them to screen the blood samples rapidly for the presence of autoantibodies against 40 TAAs associated with breast cancer, and also 27 TAAs that were not known to be linked with the disease.
Presenting the research at the NCRI Conference, Ms Daniyah Alfattani, a PhD student in the group, said: “The results of our study showed that breast cancer does induce autoantibodies against panels of specific tumour-associated antigens. We were able to detect cancer with reasonable accuracy by identifying these autoantibodies in the blood.”
The researchers identified three panels of TAAs against which to test for autoantibodies. The accuracy of the test improved in the panels that contained more TAAs. The panel of five TAAs correctly detected breast cancer in 29% of the samples from the cancer patients and correctly identified 84% of the control samples as being cancer-free. The panel of seven TAAs correctly identified cancer in 35% of cancer samples and no cancer in 79% of control samples. The panel of nine antigens correctly identified cancer in 37% of cancer samples and no cancer in 79% of the controls.
“We need to develop and further validate this test,” said Ms Alfattani. “However, these results are encouraging and indicate that it’s possible to detect a signal for early breast cancer. Once we have improved the accuracy of the test, then it opens the possibility of using a simple blood test to improve early detection of the disease.”
The researchers are now testing samples from 800 patients against a panel of nine TAAs, and they expect the accuracy of the test to improve with these larger numbers.
“A blood test for early breast cancer detection would be cost effective, which would be of particular value in low and middle income countries. It would also be an easier screening method to implement compared to current methods, such as mammography,” said Ms Alfattani.
The researchers estimate that, with a fully-funded development programme, the test might become available in the clinic in about four to five years.
A similar test for lung cancer is currently being tested in a randomised controlled trial in Scotland, involving 12,000 people at high risk of developing lung cancer because they smoke. They have been randomised to have (or not) an autoantibody blood test called ELISA (Early CDT-Lung). Participants who test positive for the autoantibodies are then followed up with a CT scan every two years in order to detect lung cancer in its early stages when it is easier to treat.
The CEAC group is also working on similar tests for pancreatic, colorectal and liver cancers. Solid tumours like these, as well as lung and breast cancer, represent around 70% of all cancers.
“A blood test capable of detecting any of these cancers at an early stage is the over-riding objective of our work,” concluded Ms Alfattani.
Dr Iain Frame, CEO of NCRI said: “Early diagnosis using simple, non-invasive ways of detecting the first signs of cancer is a key strategic priority for NCRI and something we’d all like to see working in practice. The results from this pilot study for a blood test to detect early breast cancer are promising and build on this research group’s expertise in other cancers, such as lung cancer. It’s obviously early days but we look forward to seeing the results from the larger group of patients that are now being investigated.”
More people are being diagnosed with and dying from liver cancer in England than ever before, according to new research presented at the 2019 NCRI Cancer Conference.
In 20 years, from 1997 to 2016, incidence and deaths from the most common form of the disease, hepatocellular carcinoma (HCC), have tripled and it is most common among the most deprived members of society.
Dr Anya Burton, a cancer epidemiologist at Public Health England, told the conference: “The incidence of hepatocellular carcinoma in England is increasing rapidly – it has tripled in the past 20 years. The presence of cirrhosis, particularly advanced cirrhosis, in many patients means treatment options are severely limited. Our findings highlight the urgent need to address prevention strategies for both liver disease generally and hepatocellular carcinoma specifically.”
Dr Burton and colleagues are part of the Hepatocellular Carcinoma UK / National Cancer Registration and Analysis Service (HCCUK/NCRAS) partnership that was created in 2017. NCRAS (part of Public Health England) collates and maintains data on tumours, patients, diagnosis and treatment of cancer, which the researchers are analysing through the partnership to undertake a wide range of research into this increasingly common cancer, including understanding regional variations in HCC. The current findings are for England, but the researchers are working with others in Scotland, Wales and Northern Ireland to produce UK-wide data.
They found that 62,125 cases of primary liver cancer (cancer that originates in the liver) were diagnosed in England between 1997 and 2016. Of these, 48% (29,906) were HCC, 38% intrahepatic cholangiocarcinoma (iCCA) and 14% were unspecified or other rare subtypes.
Dr Burton said: “Over the 20 years, rates of HCC have increased dramatically, but also tumour classification has improved. The proportions of the different types of liver cancer have changed during this time. In 1997 there was approximately one HCC case for every one iCCA case and 20% of tumours were unspecified. By 2016 there were 1.6 HCC cases for every one iCCA case and 11% of tumour were unspecified.”
Among men, there were 2.73 cases of HCC diagnosed and 1.93 deaths per 100,000 of the population in 1997, but by 2016 this had increased to 8.82 and 5.97 respectively, per 100,000. Among women, there were 0.82 cases diagnosed and 0.51 deaths per 100,000 of the population in 1997; this increased to 2.2 and 1.4 respectively in 2016, per 100,000. 
Overall, 25% of HCC cases were from the most deprived fifth of the population; of these at least 58% of cases had cirrhosis and, of these, 42% had decompensated cirrhosis, the most severe form when the liver has developed so much scarring that complications set in.
Dr Burton said: “It is well known that HCC is more common in men than in women and the reasons for this are not well understood, but may be to do with the different distribution of factors that can increase the risk across the genders. This research does not seek to address this. For HCC, the average age at diagnosis was 68.4 years and 77.2% of cases were male. Common HCC risk factors, such as high alcohol consumption, injecting drug use and obesity, are more common in deprived populations, but this has not been examined in the current analysis. Further work planned within the partnership will seek to explore the distribution of risk factors in the HCC population.”
The researchers found that the majority of HCC patients did not receive specific anti-cancer treatment. The most common routes to diagnosis were emergency presentation (35%) and GP referral (30%), and less than half of patients were alive a year after diagnosis.
Liver cancer is an aggressive cancer that is not easy to detect in its early stages. This means that many people are diagnosed when it is advanced and it is not possible to treat it by surgery because it has already started to spread to other parts of the body. In addition, cirrhosis reduces liver function and so treating a patient with a liver that is not working properly has a high risk of further complications, including liver failure. If liver cancer is detected an early stage it can be treated by means of surgery, radiofrequency ablation or liver transplantation.
Mr Hassan Malik is chair of the NCRI Hepatobiliary workstream of the Upper Gastrointestinal Group and a consultant hepatobiliary surgeon at the University Hospital Aintree, Liverpool, UK. He was not involved in the research. He said: “The tripling of liver cancer in the past 20 years is extremely worrying and these data are a wake-up call to policy-makers and health providers that better prevention strategies are urgently needed. Although these new figures apply only to England, we know that alcohol, drug abuse and the resulting liver cirrhosis are an issue in other areas of the country and so HCC rates are likely to be higher.
“Prevention is always better than cure, and this is particularly the case for liver cancer, which is usually only detected in its advanced stages when it’s almost impossible to cure. This important piece of work may influence policy-makers in supporting additional resources for the prevention and treatment of all types of primary liver cancers.”
Men with higher levels of ‘free’ testosterone and a growth hormone in their blood are more likely to be diagnosed with prostate cancer, according to research presented at the 2019 NCRI Cancer Conference.
Other factors such as older age, ethnicity and a family history of the disease are already known to increase a man’s risk of developing prostate cancer.
However, the new study of more than 200,000 men is one of the first to show strong evidence of two factors that could possibly be modified to reduce prostate cancer risk.
The research was led by Dr Ruth Travis, an Associate Professor, and Ellie Watts, a Research Fellow, both based at the University of Oxford, UK. Dr Travis said: “Prostate cancer is the second most commonly diagnosed cancer in men worldwide after lung cancer and a leading cause of cancer death. But there is no evidence-based advice that we can give to men to reduce their risk.
“We were interested in studying the levels of two hormones circulating in the blood because previous research suggests they could be linked with prostate cancer and because these are factors that could potentially be altered in an attempt to reduce prostate cancer risk.”
The researchers studied 200,452 men who are part of the UK Biobank project. All were free of cancer when they joined the study and were not taking any hormone therapy.
The men gave blood samples that were tested for their levels of testosterone and a growth hormone called insulin-like growth factor-I (IGF-I). The researchers calculated levels of free testosterone – testosterone that is circulating in the blood and not bound to any other molecule and can therefore have an effect in the body. A subset of 9,000 of men gave a second blood sample at a later date, to help the researchers account for natural fluctuations in hormone levels.
The men were followed for an average of six to seven years to see if they went on to develop prostate cancer. Within the group, there were 5,412 cases and 296 deaths from the disease.
The researchers found that men with higher concentrations of the two hormones in their blood were more likely to be diagnosed with prostate cancer. For every increase of five nanomoles in the concentration of IGF-I per litre of blood (5 nmol/L), men were 9% more likely to develop prostate cancer. For every increase of 50 picomoles of ‘free’ testosterone per litre of blood (50 pmol/L), there was a 10% increase in prostate cancer risk.
Looking at the population as a whole, the researchers say their findings correspond to a 25% greater risk in men who have the highest levels of IGF-I, compared to those with the lowest. Men with the highest ‘free’ testosterone levels face a 18% greater risk of prostate cancer, compared to those with the lowest levels.
The researchers say that because the blood tests were taken some years before the prostate cancer developed, it is likely that the hormone levels are leading to the increased risk of prostate cancer, as opposed to the cancers leading to higher levels of the hormones. Thanks to the large size of the study, the researchers were also able to take account of other factors that can influence cancer risk, including body size, socioeconomic status and diabetes.
Dr Travis said: “This type of study can’t tell us why these factors are linked, but we know that testosterone plays a role in the normal growth and function of the prostate and that IGF-I has a role in stimulating the growth of cells in our bodies.”
“What this research does tell us is that these two hormones could be a mechanism that links things like diet, lifestyle and body size with the risk of prostate cancer. This takes us a step closer to strategies for preventing the disease.”
Dr Travis and Ms Watts will continue examining the data from this study to confirm their findings. In the future, they also plan to home in on risk factors for the most aggressive types of prostate cancer.
Professor Hashim Ahmed, chair of NCRI’s prostate group and Professor of Urology at Imperial College London, who was not involved in the research said: “These results are important because they show that there are at least some factors that influence prostate cancer risk that can potentially be altered. In the longer term, it could mean that we can give men better advice on how to take steps to reduce their own risk.
“This study also shows the importance of carrying out very large studies, which are only possible thanks to the thousands of men who agreed to take part.”