From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer^†

Introduction: Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3–6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. Methods: Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. Results: 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/− risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3–6 months after finishing treatment. At 3–6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. Conclusions: ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.