Computationally Optimized ctDNA Surveillance for Recurrence Detection in HPV-Positive Head and Neck Squamous Cell Carcinoma

IMPORTANCE: Early detection of Head and Neck Squamous Cell Carcinoma (HNSCC) recurrence in HPV-positive patients is crucial for improving survival rates and reducing treatment costs. Integrating circulating tumor DNA (ctDNA) testing as part of post-treatment surveillance may enhance timely cancer recurrence detection, reduce false-positive rates, and lower overall costs. OBJECTIVE: To develop and evaluate personalized, cost-effective post-treatment surveillance strategies that integrate ctDNA testing with established, computed tomography (CT) scans, with the goal of minimizing costs and treatment delays for HPV-positive HNSCC patients. METHODS: We constructed a microsimulation model that optimizes the timing of ctDNA tests and generates testing schedules designed to achieve detection delays below specified thresholds at a minimum cost. The model was fit using n= 840 training data and validated using n= 447 external data. Six sub-populations were created based on the combination of cancer stage (AJCC 8th edition stage 1, stage 2, and stage 3) and smoking status (non-smoker and ever-smoker). The study compared the proposed ctDNA-based strategy with established clinical guidelines, as well as a strategy from the literature. RESULTS: Our optimization model generated cost-effecive strategies for scheduling ctDNA tests for a range of detection delay tolerances (i.e., 3, 6, and 9 months) across the six subpopulations. The optimal ctDNA-based strategy demonstrated substantial cost savings, potentially reducing annual surveillance costs in the USA by at least $200 million compared to imaging-based guidelines, while matching an equal patient outcome of treatment delay. Additionally, a hypothetical scenario of monthly ctDNA testing, incurring comparable total cost to the existing guidelines’, offers a 32% reduction in treatment delay. The study also highlighted the growing importance of HPV-positive HNSCC surveillance, with the annual incidence projected to rise, further emphasizing the cost-saving potential of ctDNA integration. CONCLUSION: Integrating ctDNA testing with traditional imaging methods for post-treatment surveillance of HPV-positive HNSCC patients offers a cost-effective strategy that minimizes surveillance costs and treatment delays. As the HPV-positive HNSCC population grows, the significance of the cost savings will increase. Future research should focus on the applicability of the developed strategy and their impact on patient survival and quality of life.