The Early Detection of Hepatocellular Liver Cancer
Project overview and Aims
Cancer that begins in the liver (hepatocellular carcinoma) is one of the fastest rising and fourth commonest cause of deaths due to cancer world-wide. Liver cancer is usually associated with liver viral infections, alcohol and obesity, causing the immune system to attack the liver leading to scarring and liver nodules (liver cirrhosis).
We know that changes throughout the cirrhotic liver tissue are the major risk factor for liver cancer, but we do not understand the nature of these changes, or why and when some people develop cancer and others do not. In some people a “field affect” appears to arise throughout the cirrhotic liver leading to a high risk of developing liver cancer. So far, little effort has been made to characterise these changes.
Currently, the tests (ultrasound scan and sometimes a single blood test [AFP]) that we use to diagnose liver cancer at an early stage, when the cancer can be treated, fail in 6 out of 10 people. As a result the vast majority of people are first diagnosed when their cancer is too advanced to be treated.
Our Aims: In this programme, we aim to 1) better understand the changes within the liver that lead to cancer and 2) to detect liver cancer at the earliest stages when curative therapies may be applied.
We will take samples of the liver from people with and without liver cancer, in a safe procedure that uses very fine needles and compare how cells in the liver are functioning in great detail (Delphi).
In a study of patients with small HCC (SeLINA) we will use new imaging technologies to assess the whole liver to identify those at most risk of cancer and to detect small tumours early. We will also measure proteins that are already known to be associated with liver cancer and other biomarkers in the blood, using the most promising technologies available. We will include 200 people with cirrhosis and 50 people with HCC without cirrhosis, all with HCC.
Finally, we will develop an exciting new blood test (TAPS), that can measure changes in DNA (the building blocks of cells) that is released from the liver cancer, or the liver at risk of cancer, into the blood : Further information click on these links.
Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution - PubMed (nih.gov)
Cell-free DNA TAPS provides multimodal information for early cancer detection - PubMed (nih.gov
In parallel we will establish the first UK wide prospective cohort of patients with cirrhosis, followed annually for 5 years with annual blood sampling. Of these, we anticipate that a subset will develop HCC. We will interrogate the blood samples collected for HCC early detection markers, and perform host genetic and viral sequence analysis to identify HCC genetic risk factors. The cirrhosis study will build on the pre-existing STOP-HCV cirrhosis study.
To achieve this, we have gathered a team of internationally renowned scientists with different but complimentary skills to maximise the chances that our project will be successful. Our team also includes experts in managing and combining the data that we will generate. We believe that our approach will lead to a much better understanding of the biological reasons for the development of liver cancer. We hope also that in using the best combination of the most promising tests, we will be able to identify cancer at the very earliest stages so that people can be cured.
The consortium work is funded by a 5-year Cancer Research UK Early Detection Programme Award and is led by Professor Eleanor Barnes at the Peter-Medawar-Building, Nuffield Department of Medicine, University of Oxford.