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2018 ASTRO: Liquid Biopsy in HPV-Associated Oral Cancer Surveillance

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Key Points

  • Following the 3-month post-CRT scans, 73 of the 89 patients in the surveillance cohort had undetectable levels of ctHPVDNA at every follow-up visit.
  • The remaining patients developed a positive ctHPVDNA test result with a median interval from CRT of 16.7 months and a median value of 75 copies/mL.
  • Eight of the patients who developed a positive test result were diagnosed with cancer recurrence (0 local, 1 regional, 7 distant). The other patients showed detectable levels of ctHPVDNA but no other evidence of cancer recurrence; they are being monitored with repeat blood tests and imaging.

A highly sensitive blood test that detects minute traces of cancer-specific DNA has been shown to accurately determine whether patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) are free from cancer following radiation therapy. Findings were presented by Chera et al at the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA6).

The liquid biopsy test, which measures fragments of DNA shed by cancers cells in the blood, could save thousands of dollars per patient by reducing the need for costly radiologic studies such as positron emission tomography (PET)/computed tomography (CT) scans following radiation therapy.

“We’ve developed a highly specific, sensitive liquid biopsy blood test for people with HPV-associated OPSCC,” said Bhisham Chera, MD, Associate Professor of Radiation Oncology at the University of North Carolina (UNC) at Chapel Hill and a member of the UNC Lineberger Comprehensive Cancer Center, in a statement. “This blood test had exceptional performance in monitoring patients for cancer recurrence after radiation therapy. If the circulating tumor HPV DNA is undetectable, there is a high likelihood that the patient is in remission and cancer-free.”

Radiation therapy has been shown to be a highly effective treatment for HPV-related OPSCC, but patients must be monitored for recurrence for up to 5 years to ensure their cancer doesn’t return.

Liquid Biopsy

The liquid biopsy test developed by Dr. Chera and his colleagues to monitor patients following radiation therapy is a digital polymerase chain reaction assay for HPV DNA that is highly specific, in that it does not cross-detect other types of cellular DNA; precise, in that it can be consistently reproduced; and sensitive, in that it has the ability to detect as few as six molecules of HPV DNA in a blood sample.

The test was able to predict whether a patient was cancer-free with very high accuracy, indicated by a negative predictive value of 100%. That type of accuracy in a liquid biopsy test, explained Dr. Chera, could potentially reduce the need for costly radiologic studies during posttreatment surveillance, reserving them only for patients with detectable circulating tumor HPV DNA (ctHPVDNA).

Trial Findings

This prospective biomarker trial included 89 patients with HPV-associated OPSCC with no distant metastases. All patients received definitive chemoradiation therapy (CRT), with 78 receiving de-intensified CRT to 60 Gy total radiation dose and 11 receiving standard CRT to 70 Gy.

Beginning 3 months after treatment completion, patients were monitored with a combination of PET/CT scans, CT scans, and chest x-rays every 6 months. Additionally, patients underwent clinical exams every 2 to 4 months for 2 years, and every 6 months for the following 3 years. The average follow-up time for patients on the study was 19.8 months (range, 3.7–44.7).

Blood was drawn and tested for ctHPVDNA in all patients during each follow-up visit after treatment. If ctHPVDNA was detected, additional imaging tests were performed.

Following the 3-month post-CRT scans, 73 of the 89 patients in the surveillance cohort had undetectable levels of ctHPVDNA at every follow-up visit. The remaining 16 patients developed a positive ctHPVDNA test result with a median interval from CRT of 16.7 months (range, 7.8–30.4) and a median value of 75 copies/mL (range, 9–28,369). Eight of the patients who developed a positive test result were diagnosed with cancer recurrence (0 local, 1 regional, 7 distant). The other patients showed detectable levels of ctHPVDNA (range, 23–28,369 copies/ml) but no other evidence of cancer recurrence; they are being monitored with repeat blood tests and imaging.

The test could provide patients with much-needed peace of mind, said Dr. Chera. “We are showing in this abstract that the blood test performs very well. It detects cancer before the scan detects cancer. Using this test, I can walk into a patient’s room and say, ‘You are more than likely cancer-free at this point.’”

In the future, ctHPVDNA testing may also potentially be used to screen for cervical cancer or anal cancer, which are also frequently associated with HPV infection, the authors said. They recommend further research to see if it could improve early detection of cancer recurrence and reduce costs by targeting radiographic surveillance to the subset of patients who are at greatest risk of relapse.

Intellectual property related to the test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Dr. Chera and Dr. Gupta hold equity stakes.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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