After cervical chemoradiation, liquid biopsy can identify any remaining disease.

A new study shows that two liquid biopsy techniques that detect the presence of human papillomavirus (HPV) in the blood accurately identify patients at high risk of cervical cancer recurrence after chemoradiation.

The findings are presented at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The study compared two new tests – a digital polymerase chain reaction (dPCR) test and a sequencing test for genetic material from HPV, the main cause of cervical cancer – and found that they detect residual disease in the blood of recently diagnosed patients. was equally effective in identification. Completed radiation and chemotherapy for cervical cancer. Early detection allows early treatment of residual disease and better chances of survival.

“These non-invasive tests can detect residual disease after chemoradiation treatment before imaging or clinical examination,” said lead study author Kathy Hahn, MD, a radiation oncologist at the Princess Margaret Cancer Center at the University of Toronto. “We can detect the disease much earlier, before it becomes larger, which will potentially enable us to intervene earlier and improve outcomes for people with cervical cancer.”

About 11,500 new cases of cervical cancer are diagnosed each year in the U.S., and an estimated 4,000 Americans die from the disease each year. Approximately 30–40% of cervical cancer patients develop tumor recurrence after chemoradiation, and currently, residual disease is often detected too late to improve survival rates.

Tissue biopsy has long been considered the gold standard for identifying tumors, but it requires an invasive procedure to sample enough tumor tissue to be seen on imaging, and it only provides a snapshot of a specific tumor area. Provides. Liquid biopsy can detect microscopic components of a tumor in bodily fluids such as blood or urine, providing a less invasive option for assessing malignancy. The blood test is the most widely used type of liquid biopsy and can identify circulating tumor DNA (ctDNA), circulating RNA, and other markers that indicate the presence of cancer, including HPV.

Because these tests can detect fragments of the HPV virus that remain in the blood after chemoradiation but before tumors recur, “liquid biopsies provide insight before tissue biopsies are possible,” Dr. Han said. “If we can predict who might be at greater risk of recurrence, it could be a signal to physicians to make sure these patients are followed more closely.”

In a previous pilot study, Dr. Han and his team collected blood samples from 20 patients with cervical cancer before and after chemoradiation treatment. Using digital polymerase chain reaction (dPCR) tests, they found that people with detectable HPV ctDNA at the end of chemoradiation had worse outcomes than people with no detectable HPV ctDNA.

This new study sought to validate those findings in a larger sample of patients using both dPCR and more sophisticated HPV sequencing tests. To do this, researchers prospectively enrolled 70 patients from four Canadian centers; All participants were diagnosed with HPV-positive cervical cancer and treated with chemoradiation. Patients were followed for an average of 2.2 years.

Patients gave blood samples before treatment; They also had blood tests done immediately after treatment, after four to six weeks of treatment, and after 12 weeks of treatment. Patients with detectable HPV ctDNA in their blood at each of these three-time points had significantly worse progression-free survival rates than those with no detectable HPV in their blood.

Specifically, 53% of patients with detectable HPV ctDNA immediately after chemoradiation were progression-free after two years, compared with 87% of patients without detectable HPV ctDNA immediately after treatment. The difference was even more pronounced at the 12-week mark; Patients with detectable HPV ctDNA three months after chemoradiation had a 26% two-year progression-free survival rate, compared with 85% in those without progression.

“We are pleased to see that we can validate our preliminary results,” said Dr. Han. “However, we were surprised to find no significant difference between the digital PCR test and the HPV sequencing test. Even though HPV sequencing was more sensitive than digital PCR, both methods gave similar results after treatment.

In recent years, advances in technology have accelerated the use of liquid biopsy, which is believed to have great potential for non-invasive cancer screening in high-risk populations. However, tests are not yet widely available.

Dr. Han said one of the challenges in making HPV ctDNA testing widely available for people with cervical cancer is the diversity of HPV types that cause the disease, adding that their analysis included 11 different HPV types. was detected. Yet Dr. Han said the HPV sequencing test is capable of detecting all 11 types with high accuracy and suggested it could become a common approach to HPV-positive cervical cancer.

Expanding access to liquid biopsies is also essential, Dr. Han said, and important for future research using liquid biopsies to identify patients at higher risk of recurrence and randomize them to intensive versus standard treatment. will be.

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