Two liquid biopsy tests designed to detect the human papillomavirus (HPV) in the blood may accurately identify patients at high risk of cervical cancer recurrence following the completion of chemoradiation, according to new findings presented by Han et al at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 105).
Background
There are about 11,500 newly diagnosed cases of cervical cancer and 4,000 deaths from the disease in the United States each year. Approximately 30% to 40% of the patients with cervical cancer develop tumor recurrence following chemoradiation, and currently, residual disease is often detected too late to improve survival rates.
Tissue biopsies have long been the standard for identifying these tumors; however, the tests require an invasive procedure to sample enough tumor tissue to be visualized on imaging, which only provide a snapshot of a specific tumor region. Liquid biopsies can detect microscopic components of tumors in bodily fluids such as blood or urine, providing a less invasive option to assess cervical cancer. Blood tests are the most widely used type of liquid biopsy and can identify circulating tumor DNA (ctDNA), circulating RNA, and other markers—such as HPV—that signal the presence of cancer.
These tests are capable of detecting fragments of HPV that remain in the blood following chemoradiation but before cancer recurrence. Because HPV is the most common cause of cervical cancer, earlier detection may allow for earlier treatment of residual disease and potentially improve survival rates.
“[L]iquid biopsies provide insight before tissue biopsy becomes possible,” explained lead study author Kathy Han, MD, a radiation oncologist at the Princess Margaret Cancer Center at the University of Toronto. “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 highlighted.
In a previous study, Dr. Han and her colleagues collected blood samples from 20 patients with cervical cancer prior to and following chemoradiation. Using digital polymerase chain reaction tests, they found that patients with detectable HPV ctDNA at the end of chemoradiation had worse outcomes than those with no detectable HPV ctDNA.
Study Methods and Results
In the new study, researchers recruited 70 patients with HPV-positive cervical cancer who had undergone treatment with chemoradiation and compared the digital polymerase chain reaction test with a more sophisticated sequencing test for genetic material from HPV—with the goal of validating their previous findings.
The researchers collected blood samples prior to treatment and took blood tests immediately following treatment—from 4 to 6 weeks and 12 weeks posttreatment.
After a median follow-up of 2.2 years, the patients with detectable HPV ctDNA in their blood at each of these three timepoints had substantially worse progression-free survival rates than those with no detectable HPV in their blood.
Specifically, 53% of the patients with detectable HPV ctDNA immediately following chemoradiation experience 2-year progression-free survival compared with 87% of the patients without detectable HPV ctDNA immediately following treatment. The differences were even more pronounced at the 12-week mark—where the patients with detectable HPV ctDNA following chemoradiation had a 26% 2-year progression-free survival rate compared with 85% of those without detectable HPV ctDNA.
The researchers also found that both tests were comparable in their ability to identify residual disease in the patients’ blood.
Conclusions
“We were happy to see that we could validate our initial results. We were surprised, however, to find no significant differences between the digital [polymerase chain reaction] test and the HPV sequencing test. Even though HPV sequencing was more sensitive than digital [polymerase chain reaction], both approaches returned similar results after treatment,” Dr. Han noted.
Although advances in technology have accelerated the use of liquid biopsies—which are believed to hold great potential for noninvasive cancer screenings in high-risk populations—the tests are not yet widely available.
One of the challenges with making HPV ctDNA testing more accessible to patients with cervical cancer is the variety of HPV strains that cause disease. The researchers detected 11 distinct HPV strains in their analysis. Nonetheless, the HPV sequencing test was capable of detecting all 11 types with high accuracy, suggesting that it may become a generalizable approach for patients with HPV-positive cervical cancer.
The researchers emphasized that expanding access to liquid biopsies may be crucial for future research using liquid biopsies to identify patients at high risk of recurrence and randomizing them to intensive vs standard treatment.
“These noninvasive tests can detect residual disease following chemoradiation treatment earlier than imaging or a clinical exam,” underscored Dr. Han. “We can detect very minimal disease before it grows bigger, which potentially will enable us to intervene earlier and improve outcomes for [patients] with cervical cancer,” she concluded.
Disclosure: For full disclosures of the study authors, visit redjournal.org.
