NavDx (ctHPVDNA) recurrence detection in surgically treated human papillomavirus-associated oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV+)-positivity in oropharyngeal squamous cell carcinoma (OPSCC) is a favorable prognostic indicator though 10–25% of patients will experience progressive disease within 3 years of treatment. This project assesses the validity of circulating tumor HPV DNA (ctHPVDNA) surveillance in patients following definitive surgical treatment. A retrospective review of patients with HPV+ OPSCC treated with definitive resection at a single institution between 2020 and 2023 was performed. Patients underwent standard post treatment imaging (CT neck and chest and/or PET/CT). ctHPVDNA samples were also collected. Imaging response was assessed via NI-RADS (Neck Imaging Reporting and Data System) risk classification and independently reviewed. The cohort included 16 patients (15 primary, 1 recurrent): 81% males; median age 58; 56% never smokers, 38% former smokers, 6% current smokers; 63% tonsil primary, 31% BOT; 38% T1, 19% T2, 44% Tx; 0% N0, 25% N1, 38% N2a, 31% N2b, 0% N2c, 6% N3 (AJCC 7th edition). Four patients (25%) experienced biopsy-proven recurrence (13% locoregional, 13% distant) with a median time to recurrence of 14 months (range 3–42). NI-RADS suggested 4 locoregional recurrences (1 true positive, 3 false positive) yielding 50% sensitivity, 75% specificity, 25% PPV, 90% NPV. ctHPVDNA identified 2 locoregional events, and 2 distant events (4 true positive, 0 false positive) yielding 100% sensitivity, 100% specificity, 100% PPV, 100%. Surveillance ctHPVDNA more accurately identified recurrences with minimal false positives compared to post-treatment imaging, which may limit the need for repeat imaging and unwarranted salvage operations which increase patient worry, morbidity, and financial toxicity. 4