Genetic research, liquid biopsy conceptual illustration

In a new study presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, researchers have confirmed the effectiveness of two liquid biopsy tests in identifying patients at high risk of cervical cancer recurrence after completing chemoradiation. The tests, a digital polymerase chain reaction (dPCR) and a sequencing test for genetic material from the human papillomavirus (HPV), the primary cause of cervical cancer, were found to be equally effective in detecting residual disease in the blood.

“These non-invasive tests can detect residual disease following chemoradiation treatment earlier than imaging or a clinical exam,” says lead study author Kathy Han, MD, a radiation oncologist at the Princess Margaret Cancer Center at the University of Toronto. “We can detect very minimal disease, before it grows bigger, which potentially will enable us to intervene earlier and improve outcomes for people with cervical cancer.”

The authors note that there are advantages to taking a liquid biopsy approach to looking for cancer recurrence, over the gold standard method of tissue biopsies. Tissue biopsies are invasive and require sampling enough tumor tissue to be seen via imaging, while also providing only a small snapshot of the disease in the tumor region where the sample came from.

Liquid biopsies have the advantage of detecting very small components and quantities of ctDNA, circulating RNA, and other biomarkers of disease that can provide an early signal of the presence of cancer and HPV. Because the liquid biopsies can detect fragments of the HPV virus that remain in the blood following chemoradiation, but before the tumors recur, they can provide actionable insights before tissue biopsy is even an option, Han notes.

“If we can predict who might be at higher risk of recurrence, it may be a signal to clinicians to make sure these patients are followed more closely,” she adds.

The new research is a follow up to a pilot study that collected blood samples from 20 cervical cancer patients both before, and after, chemoradiation treatments. Using dPCR, Han and team found that patients with detectable HPV ctDNA after chemoradation had worse outcomes than those with no detectable HPV ctDNA.

The new study was launched to validate the pilot’s results and involved 70 patients from four Canadian centers who were diagnosed with HPV-positive cervical cancer and treated with chemoradiation. Patients were followed for a median of 2.2 years. Patients gave blood samples before treatment, immediately following treatment, between four to six weeks post treatment, and 12 week post treatment.

Patients with detectable HPV ctDNA showed substantially worse progression-free survival rates than those without detectable HPV: 53% of patients with detectable HPV ctDNA immediately following chemoradiation were progression-free two years later, compared with 87% of patients without detectable HPV ctDNA immediately after treatment; at the 12 weeks patients with detectable HPV ctDNA three months following chemoradiation had a 26% two-year progression-free survival rate, compared to 85% for those without.

“We were happy to see that we could validate our initial results,” says Han. “We were surprised, however, to find no significant differences between the digital PCR test and the HPV sequencing test. Even though HPV sequencing was more sensitive than digital PCR, both approaches returned similar results after treatment.”

One of the challenges with making HPV ctDNA testing widely available for people with cervical cancer is the variety of HPV types that cause the disease, Han notes. Eleven distinct HPV types were detected in their analysis and the HPV sequencing test was capable of detecting all 11 types with high accuracy suggesting it could become a generalizable approach for HPV-positive cervical cancer.

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