Three new methods for early cancer detection

Thursday, 14 November, 2019

Three new methods for early cancer detection

The UK’s National Cancer Research Institute (NCRI) has announced several promising new methods for detecting cancer early, as detailed at the 2019 NCRI Cancer Conference.

Blood test for breast cancer

The first of these methods, developed by researchers at the University of Nottingham, suggests that 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.

Cancer cells produce proteins called antigens that trigger the body to make antibodies against them — autoantibodies. Nottingham researchers found that these tumour-associated antigens (TAAs) are good indicators of cancer, and have now 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 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.

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 Daniyah Alfattani, a PhD student in the group. “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. The researchers estimate that, with a fully funded development program, the test might become available in the clinic in about four to five years.

“A blood test for early breast cancer detection would be cost-effective, which would be of particular value in low- and middle-income countries,” Alfattani said. “It would also be an easier screening method to implement compared to current methods, such as mammography.”

Non-invasive sampling for cervical pre-cancer

Researchers from the Queen Mary University of London have meanwhile developed a non-invasive test to detect cervical pre-cancer by analysing urine and vaginal samples collected by the women themselves, serving as an alternative to Pap smears for those who have tested positive for human papilloma virus (HPV).

“[HPV testing] 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,” noted Queen Mary’s Dr Belinda Nedjai. “The choice of an appropriate strategy for high-risk HPV-positive women is a key issue.”

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.

Dr Nedjai and her colleagues developed the ‘S5’ test to measure 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 — the higher the score, the higher the risk.

Earlier research showed that when S5 was used on cervical samples collected by healthcare 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. The researchers subsequently decided to assess whether S5 could identify women who had CIN3 pre-cancer lesions using urine and vaginal samples.

A total of 620 women who had experienced abnormal smear test or positive HPV results provided vaginal samples for the study, 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 first tested S5 as a secondary test on HPV-positive women to limit the number of patients sent to colposcopy,” Dr Nedjai said. “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.”

Dr Nedjai said the self-sampling test proved popular with women taking part in the study and this meant that it was likely to improve participation 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 program in their country”.

AI blood test for brain tumours

Finally, a Scottish research team has combined chemical analysis of blood samples with an artificial intelligence program to speed up the diagnosis of brain tumours, which reduce life expectancy by an average of 20 years — the highest of any cancer.

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. The newly developed 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.

“We know that 62% of patients are diagnosed in the emergency department, even though they may have seen their GP several times beforehand,” said Dr Paul Brennan from the University of Edinburgh. “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 worked with the University of Strathclyde’s Dr Matthew Baker, who serves as Chief Scientific Officer at ClinSpec Diagnostics, 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 infrared spectroscopy to examine the chemical make-up of a person’s blood, combined with an AI program that can spot the chemical clues that indicate 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. 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. In the case of the most common form of brain tumour — glioma — the test was 92% accurate at picking up which people had 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.

“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,” Dr Baker said. “This could ultimately speed up diagnosis, reduce the anxiety of waiting for tests and get patients treated as quickly as possible.”

The researchers say 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 emergency department. They 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.

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