Anal cancer is one of the rarest cancers in the U.S., but this means it can be difficult to screen, and get good treatment. Its numbers are growing in women, men who have sex with men, and people with HIV; these stats call for a less invasive, and inexpensive way to diagnose anal lesions. Now, researchers at Queen Mary University of London have identified two biomarker genes that can accurately indicate whether a patient's lesions will progress to anal cancer.

The study, published in Oncotarget, found all of the anal cancers showed the presence of specific epigenetic methylation markers on the patients' EPB41L3 gene — a tumor suppressor gene — and on certain regions of their viral HPV genome. In other words, the researchers found specific genetic markers in the patients' epigenetics, which describes the naturally-occurring chemical "tags" on genes that control whether or not they are switched on. Here, the team developed a test, based on the patient's epigenetics, to identify those with the highest risk of anal cancer.

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"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," said lead researcher Professor Attila Lorincz from QMUL, in a statement.

This is important because current diagnosis methods are often uncomfortable and painful. For example, full biopsies are painful, and cytology — taking a small sample of cells — can bring issues since lesions can be hidden, and can cause different interpretations of results. Anoscopy, where the anal canal is examined using a high resolution magnifying instrument, is invasive, expensive, complicated, and can lead to subjective results.

Currently, there is no regulatory or professional group that recommends anal cancer screening for the general population. There's controversy of which patients are eligible for screening, and what techniques should be used. This has led to over-treatment of people even at low risk since it's not known which anal precancerous lesions will develop into cancer.

This means many people are undergoing these invasive and expensive procedures unnecessarily, which prompted Lorincz and her team to examine anal biopsy specimens for genetic markers in cases of anal cancer. A total of 148 patients in London, including 116 men, most of whom have sex with men, were included in the study.

After discovering epigenetic testing worked as a diagnostic tool, the researchers were able to differentiate between those at risk, and those not at risk. This will help make sure anoscopies and laser or chemical surgery is only given to those who need it. If this testing method is developed, doctors would need to take a small sample of cells from the anal canal via a swab, and then send the sample to a lab for epigenetic analysis.

But, before a test is developed, the researchers admit these findings need to be replicated with a larger sample size across the UK, and repeated using swab samples, rather than biopsies. This study highlights an interesting comparison: just as there's a link between changes to cell DNA and cervical cancer, changes to DNA in anal cells could suggest the presence of anal cancer.

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"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," said Dr. Rachel Orritt, Cancer Research UK's health information officer.

Previous research has found clinical symptoms, such as anal bleeding, and physical findings, are present in most anal cancer patients. Those with pain in the anal region, painful defecation, and weight loss are more likely to be diagnosed with the locally advanced disease. But, a swab test, similar to the one developed in the study, could help differentiate between a cancerous and noncancerous anal lesion.

In the U.S., the risk of being diagnosed with anal cancer in one's lifetime is about 1 in 500; the risk is slightly higher in women than in men. About 8,200 new cases (5,250 in women and 2,950 in men) of anal cancer are estimated in 2017, with about about 1,100 deaths (650 in women and 450 in men). This suggests the number of new anal cancer cases will continue to increase over the years.

Identifying biomarkers in diseases like anal cancer could potentially lead to the discovery of a universal set of biomarkers for any type of cancer. Moreover, this can have implications on drug therapy where techniques can help drugs target the epigenetic pathway. This can lead to better diagnosis, treatment, and potentially survival rates for anal cancer, and other cancers.

Source: Lorincz AT, Nathan M, Reuter C et al. Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions. Oncotarget. 2017.

See Also:

Anal Cancers In U.S. Triple Since '70s

Early Signs And Symptoms Of Anal Cancer No One Talks About