Although so-called liquid biopsies are now helping to determine the need for adjuvant therapy for a number of malignancies, oropharyngeal carcinoma is not yet one of them, according to a prospective pilot study from Memorial Sloan Kettering Cancer Center. The investigators evaluated the use of human papillomavirus circulating tumor DNA (HPV ctDNA) as an integral biomarker for measurable residual disease, to select patients for active surveillance.¹

“Our pilot study approach of using HPV ctDNA–based selection of oropharyngeal cancer patients for postoperative active surveillance closed early because of a high rate of gross disease recurrence—25%—and we failed to meet our primary endpoint,” said Linda Chen, MD, of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, New York, who reported the findings at the 2024 Multidisciplinary Head and Neck Cancers Symposium.¹ She noted the three radiographic recurrences were not preceded by an emergence of detectable HPV ctDNA (although two of the three cases had HPV-positive ctDNA at the time of imaging); therefore, the assay failed to provide an early signal of disease progression. “Additional data are needed to select patients for active surveillance,” she concluded.

Linda Chen, MD

The concept of using HPV ctDNA is based on its potential for identifying [occult] measurable residual disease (MRD) prior to clinically apparent recurrences. Dr. Chen and colleagues hypothesized that postoperative HPV ctDNA—as a biomarker for undetectable MRD—may help to select patients for whom omission or delay of adjuvant radiation would be a safe option. Radiation therapy would be instituted should HPV ctDNA become detectable.

Study Details

HPV ctDNA was assessed in patients using the NavDx assay, a liquid biopsy test that quantifies circulating tumor-tissue–modified viral (HPV) DNA. Investigators screened 53 HPV-positive surgical candidates, finding 12 (mostly with tonsillar cancer) who met the criteria for active surveillance: preoperative tumor-tissue–modified HPV DNA score ≥ 50 fragments/mL, surgical resection of all gross disease, at least one pathologic risk factor that warranted adjuvant therapy, no signs of disease on magnetic resonance imaging (MRI), and negative postoperative HPV ctDNA at two time points (2 and 6 weeks after surgery).

During active surveillance, patients were monitored with tumor-tissue–modified HPV DNA testing, imaging, and physical exam every 3 months, with delayed adjuvant radiation begun on study only if they developed detectable tumor-tissue–modified HPV DNA without evidence of gross disease. Patients who were found during surveillance to have developed gross disease, regardless of HPV ctDNA status, were taken off study. This active surveillance approach would be considered worthy of further study if at least 85% of evaluable patients were without evidence of gross disease at 1 year, Dr. Chen explained.

The median preoperative tumor-tissue–modified HPV DNA score of the 12 patients (enrolled before early cohort closure) was 448 fragments/mL, and median follow-up was 12.5 months.

Primary Endpoint Not Met

Of the 12 patients, 8 (67%) successfully underwent active surveillance, showing no evidence of HPV ctDNA over the 6 months of the study. Among the other four patients, one had detectable HPV ctDNA that emerged 6 months after surgery, without evidence of gross disease, and was treated with 60 Gy of radiation on study. The three other patients developed radiographically detected disease progression by the 6-month surveillance time point; two of these recurrences were synchronous with the detection of tumor-tissue–modified HPV DNA, and the other was detected radiographically before tumor-tissue–modified HPV DNA was detected.

“As 3 of the 12 patients developed gross recurrent disease, this cohort was closed because of failure to meet our primary endpoint,” Dr. Chen said. “Additional clinical factors are needed to select patients for active surveillance and initiation of delayed adjuvant therapy prior to recurrence.” 

DISCLOSURE: Dr. Chen reported that the NavDx laboratory assay used for this pilot study was provided by Naveris. 

REFERENCE

1. Chen L, Cohen M, Hatzoglou V, et al: Early disease recurrence following post-operative HPV ctDNA-directed active surveillance in oropharyngeal carcinoma: Outcomes of a prospective pilot study. 2024 Multidisciplinary Head and Neck Cancers Symposium. Abstract LBA1. Presented February 29, 2024.