Genetic test for anal cancer could identify those at high risk
A new test, based on a patient's epigenetics*, could be an accurate and inexpensive way to find and treat those at highest risk of anal cancer – a disease with growing incidence in women, men who have sex with men (MSM) and people with HIV.
The early research by Queen Mary University of London (QMUL), which was funded by Cancer Research UK, finds that the test could lead to a reduction in painful procedures and minimise the over-treatment of people at low risk.
Anal cancer is mostly caused by human papillomavirus (HPV) – the same virus that causes cervical cancer. In 2014, the UK had around 1,300 new cases of anal cancer and 360 deaths. In addition to rising levels in women and MSM, anal cancer is more common in HIV-positive MSM with around 100 cases per 100,000, compared to 25 in HIV-negative MSM, and only 1.5 in men in general.
Diagnosis presents many challenges. Full biopsies are painful, and taking a small sample of cells ('cytology') is problematic because lesions can be hidden and clinicians give varying interpretations of results. High-resolution anoscopy, where the anal canal is examined with a high resolution magnifying instrument, is often used as the primary screening tool for high-risk populations but is uncomfortable for the patient, expensive, complex and generates subjective results.
Lead researcher Professor Attila Lorincz from QMUL said: "The widespread over-treatment of anal precancerous lesions is necessary today because we don't know which ones will progress to cancer. But this creates a large burden on anoscopy clinics in the UK and the procedures can be detrimental to people's quality of life. Many people are undergoing these procedures unnecessarily, so what we really need is precision medicine to identify those who do need treatment."
The research, published in the journal Oncotarget, involved studying anal biopsy specimens from 148 patients in London, including 116 men (mostly MSM). The specimens were analysed to look for genetic markers that may be associated with the presence of anal cancer.
The team specifically looked at the patients' epigenetics and found that all of the anal cancers showed the presence of specific epigenetic methylation markers on the patients' EPB41L3 gene (a tumour suppressor gene) and also on certain regions of their viral HPV genome.
The results suggests that epigenetic testing may be an accurate and thorough method to indicate whether a patient's lesions are destined to progress to anal cancer. This could reduce the costs, pain and anxiety from other methods of diagnosis, and minimise over-treatment of low risk people.
Professor Lorincz added: "We thought this would require a complicated genomic signature involving hundreds of genes, so we were surprised that we could get such an accurate prediction from just two biomarker genes. That's important because the expected cost of the test will be fairly low.
"Now that we can identify those at risk, and conversely, those not at risk, we hope to see a big improvement, by making sure that anoscopies and laser or chemical surgery are only given to those who need it."
Once developed, the test would involve taking a small sample of cells from the anal canal via a swab and then sending the sample off to a laboratory for epigenetic analysis.
While a test could be developed within five years, the researchers caution that the results first need to be confirmed in a much larger study across the UK, and repeated using swab samples rather than the biopsies which were used in the current study.
Dr Rachel Orritt, Cancer Research UK's health information officer, said: "This study builds on what we already know about the link between changes to cell DNA and cervical cancer, and shows that similar changes to the DNA in anal cells could suggest anal cancer.
"If other studies confirm and build upon these findings, this promising research could be used to develop a less invasive method to help doctors identify people who are at a higher risk of anal cancer and avoid unnecessary procedures for those who are at a lower risk."
The researchers say that these types of biomarker – epigenetic methylation biomarkers – are important in a large number of other diseases, and could lead to a completely new approach to diagnostics and drug therapy.
Professor Lorincz explained: "These could be the early stages of a discovery of a universal set of biomarkers for any cancer. And there may be implications on therapies, as there are new techniques where the epigenetic pathway can be targeted by drugs. This is going to be the hot new area going forward in the next 15 years, so people need to be paying attention to this space."
For more information, please contact:
Joel Winston, Public Relations Manager
Queen Mary University of London
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Notes to the editor
* 'Epigenetics' describes the naturally-occurring chemical 'tags' on genes which control whether or not they are switched on. Liver cells and kidney cells are genetically identical apart from their epigenetic marks.
Research paper: 'Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions'. Attila T Lorincz, Mayura Nathan, Caroline Reuter, Rhian Warman, Mohamed A Thaha, Michael Sheaff, Natasa Vasiljevic, Amar Ahmad, Jack Cuzick, Peter Sasieni. Oncotarget.
About Queen Mary University of London
Queen Mary University of London (QMUL) is one of the UK's leading universities, and one of the largest institutions in the University of London, with 23,120 students from more than 155 countries.
A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research. In the most recent national assessment of the quality of research, we were placed ninth in the UK (REF 2014).
As well as our main site at Mile End – which is home to one of the largest self-contained residential campuses in London – we have campuses at Whitechapel, Charterhouse Square, and West Smithfield dedicated to the study of medicine, and a base for legal studies at Lincoln's Inn Fields.
We have a rich history in London with roots in Europe's first public hospital, St Barts; England's first medical school, The London; one of the first colleges to provide higher education to women, Westfield College; and the Victorian philanthropic project, the People's Palace at Mile End.
Today, as well as retaining these close connections to our local community, we are known for our international collaborations in both teaching and research.
QMUL has an annual turnover of £350m, a research income worth £125m (2014/15), and generates employment and output worth £700m to the UK economy each year.
About Cancer Research UK
* Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
* Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
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* Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
* Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
* Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
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