HPV ctDNA Testing Successfully Predicts Recurrence in Cervical Cancer

HPV ctDNA Testing Successfully Predicts Recurrence in Cervical Cancer

HPV-sequencing is a non-invasive way to identify which patients with cervical cancer are at a high risk of recurrence at the end of chemoradiation treatment, according to findings presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting.^1,2

The investigators used 2 liquid biopsy tests to measure HPV-positivity in the blood. These tests were the digital polymerase chain reaction (dPCR) test and a sequencing test for genetic material from HPV—which is the main cause of cervical cancer. The study demonstrated that these 2 measurement tools were equally effective in predicting recurrence in this patient population.

Key Findings

Patients with detectable HPV-positive circulating tumor DNA (ctDNA) immediately following treatment were substantially less likely to be progression-free across 3 distinct timepoints. For example, the percentage of patients who remained progression-free 2 years following treatment was 53% among patients who had detectable HPV ctDNA immediately following chemoradiation vs 87% among those without detectable HPV ctDNA.

At the 12-week mark, the accuracy of these tests became even more pronounced; 26% of patients with HPV-positive ctDNA were progression-free 2 years later whereas 85% of those without detectable HPV-positivity were progression-free 2 years later.

“These non-invasive tests can detect residual disease following chemoradiation treatment earlier than imaging or a clinical exam,” Kathy Han, MD, a radiation oncologist at the Princess Margaret Cancer Center at the University of Toronto, said in a press release. “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.”

These findings are based off a prospective, multicenter, validation study, which looked at 70 patients with stage IB-IVA HPV-positive cervical cancer. These individuals underwent definitive chemoradiation between 2017 and 2022. The median follow-up time was 2.2 years.

Blood samples were collected before treatment and immediately after treatment. Patients also underwent blood tests between 4 to 6 weeks posttreatment and 12 weeks posttreatment.

Significance

Historically, tissue biopsy has been the standard method for identifying tumors, although there are limitations associated with tissue biopsies. There needs to be enough tumor tissue to visualize it on an image, and it provides a snapshot only of a specific tumor regimen.

In comparison, liquid biopsies are able to detect microscopic components of tumors in bodily fluids, such as blood or urine. In cancer, blood tests are the most commonly used liquid biopsy and can identify circulating tumor DNA, circulating RNA, and other potential cancer biomarkers, including HPV.

Moreover, liquid biopsies can identify HPV virus fragments that are in the blood postchemoradiation and before tumor recurrence, helping clinicians determine which patients will need to be followed more closely.

A previous pilot study conducted by Han demonstrated that patients with detectable HPV ctNDA postchemoradiation were likely to have worse outcomes than those without detectable ctDNA. The current study was part of an effort to validate those findings in a larger sample.

“We were happy to see that we could validate our initial results,” said Dr. 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.”

Of note, the tests used in this research are not widely available yet. However, new technologies have continued to accelerate the use of liquid biopsies, and, according to Han, these may play a key role moving forward in helping identify which patients should receive intensive vs standard treatment.

References

1. Liquid biopsies can rapidly detect residual disease following cervical chemoradiation, study finds. News release. ASTRO. October 1, 2023. Accessed October 10, 2023. https://www.astro.org/News-and-Publications/News-and-Media-Center/News-Releases/2023/Liquid-biopsies-can-rapidly-detect-residual-diseas
2. Han K, Zou J, Zhao Z, et al. Clinical validation of HPV ctDNA for early detection of residual disease following chemoradiation in cervical cancer. Presented at: 2023 American Society for Radiation Oncology Annual Meeting (ASTRO); September 30 to October 4, 2023; San Diego, CA. Abstract 105.