Author: Zeena Nackerdien PhD, CME Writer, MedPage Today
In general, HPV-positive OPSCC has a favorable prognosis as compared with HPV-negative disease, which has supported efforts to de-intensify treatment regimens to reduce exposure to potentially toxic therapies. Positron emission tomography/computed tomography (PET/CT) imaging 3 months after definitive treatment is standard for response assessment in many cases.
However, the disease will recur in up to 25% of patients, depending on clinical risk factors and tumor biology. The latency period prior to OPSCC recurrence is 2 years for many patients, but rare case reports have described latency periods exceeding 5 years.
Currently, National Comprehensive Cancer Network (NCCN) guidelines recommend surveillance of patients with HPV-associated OPSCC every 1 to 3 months for the first year, every 2 to 6 months for the second year, every 4 to 8 months for years 3 to 5, and then once a year thereafter.
Because the oropharynx can be a difficult anatomic location to evaluate — a process that may be further obscured by treatment-related tissue changes — radiologic imaging studies have been used in cancer surveillance for this disease.
According to study findings published in the Journal of Clinical Oncology, a blood test for tumor-associated HPV-DNA had near-perfect accuracy for identifying OPSCC patients at high risk of recurrence after treatment.
The findings have clear and immediate implications for clinical practice, including earlier initiation of salvage therapy for patients with recurrent disease, reported Bhishamjit S. Chera, MD, of the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and colleagues.
The negative predictive value (NPV) of 100% and positive predictive value (PPV) of 99% of recurrence detection by this method compared favorably with alternative and emerging post-treatment surveillance strategies.
The findings extended those of a previous report, which showed that a persistently negative ctHPV-DNA test ruled out disease recurrence.
“With regard to how this is applicable to clinical practice, I think it improves the effectiveness, it improves the efficiency, and it reduces the cost and financial toxicity to patients,” Chera told MedPage Today.
Chera and colleagues prospectively evaluated a ctHPV-DNA liquid biopsy in 115 patients who had completed definitive chemoradiotherapy for HPV-positive OPSCC. Each patient had PET/CT imaging 3 months after finishing treatment. The researchers tested patients for ctHPV-DNA at 6- to 9-month intervals.
During a median follow-up of 23 months, 28 patients tested positive for ctHPV-DNA, indicating a possible recurrence, including 16 patients who had two consecutive positive tests. Also during follow-up, 15 patients developed biopsy-proven recurrence of OPSCC; all 15 had two consecutive positive tests for ctHPV-DNA. The median time from ctHPV-DNA positivity to recurrence was 3.9 months.
Consecutive positive tests had a PPV of 94%. The previous report from the study showed that a negative test had an NPV of 100%.
For the 87 patients who tested negative for ctHPV-DNA, none developed recurrence.
“In this study, we had accumulated enough follow-up data to see who was going to develop recurrence and who wasn’t,” said Gaorav Gupta, MD, PhD, assistant professor in the department of radiation oncology at UNC School of Medicine, in a press release. “That allowed us to determine that the test performs best if you look at two consecutively confirmed blood tests.”
Chera and team did acknowledge that heterogenous clinical factors (intensity of treatment, tobacco pack-years, use of chemotherapy) might have impacted the pattern and frequency of disease recurrence in this study. Other study limitations included the fact that the results for the ctHPV-DNA assay used in this study might not apply to alternative ctHPV-DNA assays.
Since there is no “gold standard” for surveillance imaging, the researchers chose the more stringent criterion of biopsy-proven recurrence to define a change in disease status. They added that a shorter interval between ctHPV-DNA testing (e.g., every 3 months) would more precisely define the extent of earlier detection.
Source Reference: Journal of Clinical Oncology 2020; DOI: 10.1200/JCO.19.02444
Study Highlights and Explanation of Findings:
While imaging and image-guided procedures play important roles in the screening, diagnosis, and surveillance of cancer, serial monitoring for disease recurrence can be a costly, invasive, and cumbersome process.
“We developed a technology that enabled us to distinguish HPV DNA that came from a tumor from HPV that’s simply related to infection,” said Gupta.
“The way I see this working in the clinic is that if you have a negative test, we don’t do a fiberoptic exam, we don’t order any imaging,” said Chera. “If you have a patient whose surveillance test is positive, we would bring the patient back 2 or 3 months later and repeat the blood test. If it’s positive again, then we would do an in-depth physical examination; we would do a fiberoptic exam and order a total-body PET/CT scan. This test can help us better identify which patients we can omit imaging in and those patients we can do imaging in.”
The test very well could have value in the management of patients with other types of HPV-related cancers, he said. The researchers have already examined the rate of ctHPV-DNA clearance as a biomarker for response to treatment and a possible decision-making tool for treatment de-escalation.
The testing technology has been licensed to Naveris for commercial development, and multiple medical centers have already partnered with the company to conduct studies across a variety of HPV-related diseases, said Chera.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College
Chera BS, et al “Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer” J Clin Oncol 2020; DOI: 10.1200/JCO.19.02444.
Bankhead C “Blood Test Spot On for HPV Cancer Recurrence”, MedPage Today 2020-4-09.