The so-called liquid biopsy holds great promise for detecting a variety of cancers more accurately, guiding individualized therapy, and improving monitoring during treatment. New data suggest that testing for plasma circulating tumor human papillomavirus DNA (ctHPVDNA) can be an effective method of surveillance for patients with p16-positive oropharyngeal squamous cell carcinoma (OPSCC).
The performance of an optimized multianalyte ctHPVDNA blood test for detecting cancer recurrence was "exceptional," said researchers. The test had a negative predictive value (NPV) of 100%.
"We developed an assay that is very good at detecting risk of cancer recurrence," explained lead author Bhisham Chera, MD, of the University of North Carlina at Chapel Hill (UNC) Lineberger Comprehensive Cancer Center. "Of all of the patients who had undetectable levels at follow-up, all of them are cancer free."
At a mean follow-up of 19.8 months, none of the 70 patients with undetectable ctHPVDNA at all time points during posttreatment surveillance experienced disease recurrence.
Chera presented his findings at the American Society for Radiation Oncology (ASTRO) 2018.
Liquid biopsies have generated great interest to both pathologists and oncologists, as they can potentially be used in a wide number of settings. Monitoring ctDNA is expected to provide clinicians with faster, cheaper, less invasive ways to assess cancer patients' clinical status and response to therapy.
However, an expert panel recently reported that these assay are "not yet ready for prime time in the diagnosis or management of early-stage or advanced solid tumors."
The review, which was prepared jointly by the American Society of Clinical Oncology and the College of American Pathologists, also reported that these assays are not useful, outside of clinical trials, for monitoring patients for minimal residual disease following definitive treatment of cancer or for cancer screening.
But ready or not, liquid biopsies are slowly making their way into the clinical setting. For example, cell-free DNA shed from the tumor and collected from serum is increasingly being used to direct treatment of lung cancer, both as an adjunct to biopsy of tumor tissue after drug resistance and, in some cases, as an alternative to tissue biopsy.
In head and neck oncology, UNC's Chera noted that there are data that indicate that circulating HPV DNA is detectable and can be a biomarker. In studies he has conducted, as well as studies by other researchers, findings show that the "majority of patients HPV-related tumors have detectable circulating tumor HPV DNA."
But the question, he pointed out, is whether plasma ctHPVDNA can be used to detect cancer recurrence.
Details on the 89-Patient Study
In the current study, Chera and his team developed a highly specific, sensitive liquid biopsy blood test for patients with HPV-associated OPSCC. The test, which used a standardized multistep analytic protocol to optimize specificity and sensitivity, could distinguish ctHPVDNA from native viral genomes. The current test was also able to detect ctHPV strains 16, 18, 31, 33, and 35, and Chera noted that "more high-risk strains are coming."
This prospective biomarker trial included 89 patients with HPV-associated OPSCC whose cancer had metastasized at baseline. All patients were treated with definitive chemoradiation therapy (CRT); 78 received deintensified CRT to a total radiation dose of 60 Gray (Gy), and 11 patients received standard CRT to a dose of 70 Gy.
Blood specimens were collected at baseline (58 of 89 patients) weekly during treatment (30 of 89), and with each follow-up visit (89) for extraction of plasma circulating nucleic acid. Clinical surveillance was conducted every 2 to 4 months for years 1 and 2, and then every 6 months for years 3 to 5. Chest imaging ws also performed every 6 months, and additional imaging was obtained if ctHPVDNA became detectable.
Within this cohort, 53 of 58 evaluable patients had undetectable ctHPVDNA within 3 months of completing CRT; 70 of 89 patients in the surveillance cohort had undetectable ctHPVDNA at all timepoints beyond 3 months post CRT. All 70 of these patients remained disease free, for an NPV of 100%.
For the remaining patients, 16 of 89 received a positive ctHPVDNA test result at a median of 16.7 months after CRT (median, 75 copies/mL). Within this group, eight patients were diagnosed with recurrence (no local, one regional, seven distant). Currently, eight patients have detectable ctHPVDNA (range, 23 - 28,369 copies/mL) but have no evidence of recurrence and are being monitored.
In addition, 11 patients had detectable ctHPVDNA, but no evidence of recurrent disease was found on imaging, and for four patients, the ctHPVDNA signal cleared spontaneously. The remaining seven patients continue to be closely monitored, explained Chera.
The sensitivity of ctHPVDNA testing was 100%, the specificity was 90%, the NPV was 100%, and the positive predictive value was 50%.
"In the future, I think this can help make our surveillance more effective in identifying cancer, and for those with undetectable levels, we can omit imaging," said Chera. "It can help us use diagnostic tests more appropriately."
In the future, I think this can help make our surveillance more effective.Dr Bhisham
He added that it may also allow for cancer to be detected sooner and will be more cost-effective because the use of expensive imaging can be reduced.
Additionally, ctHPVDNA testing may have applications for other malignancies associated with HPV, such as cervical cancer and anal cancer.
Validation Needed
Commenting on the study, Richard Bakst, MD, an associate professor of radiation oncology at Icahn School of Medicine at Mount Sinai, New York City, explained that "we know that HPV-related oropharyngeal cancer behaves much differently than HPV negative disease.
"While we routinely survey patients with scans to see if there is any disease remaining after treatment and/or monitor for recurrences, the results from this study suggest that we may have a more sensitive test using a circulating tumor DNA," he told Medscape Medical News. "Potentially, recurrences can be detected earlier using such a test, but it needs to be validated on a larger cohort to avoid false positive or negative results. To date, imaging tests remain the standard of care for monitoring patients with HPV-related disease."
Dr Chera has relationships with Naveris, Burroughs Wellcome Fund, the US Department of Defense, the Susan G. Komen Foundation, and the University Cancer Research Fund of UNC Linberger. Dr Bakst has disclosed no relevant financial relationships.
American Society for Radiation Oncology (ASTRO) 2018. LBA 6, presented October 23, 2018.
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