Liquid Biopsy in Head and Neck Cancer: The development of a new diagnostic tool

Head and neck cancers remain difficult to treat due to their aggressive biological behavior and delicate functional anatomy from which they arise. This particularly applies for advanced and recurrent cases, when feasible treatment options are becoming limited due to expected poor patient survival and/or functional outcome. Salvage surgery is the treatment modality of choice in case of resectable locoregional recurrence. However, recurrent head and neck squamous cell carcinoma (HNSCC) is often detected in a late stage, rendering salvage surgery with curative intent impossible. Further, for a considerable number of patients undergoing salvage surgery with curative intent, outcomes remain poor due to a high risk of complications and morbidity. Although new treatment strategies such as adjuvant immunotherapy are being developed and existing diagnostics are improving, 5-year overall survival rates of HNSCC patients in The Netherlands have remained stable at 57%-58% over the past few decades. An absolute increase in incidence from 15% to 50% of prognostically favorable HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) cases has been observed in The Netherlands in the same period, even further indicating rather stagnant survival numbers of HPV-negative HNSCC cases. This emphasizes the need for early detection of recurrent disease in order to improve chances for a successful curative treatment plan instead of a palliative regimen. In the era of emerging precision medicine, a more personalized approach to HNSCC care is desired to pave the road for new, more accurate methods of early detection of recurrence, prognostic stratification, and therapeutic response prediction. Ideally, molecular biomarkers are being used that accurately represent tumor (epi)genetic status, and at the same time allow minimally invasive collection. Lastly, this has to be practically feasible for implementation into routine clinical practice. Therefore, the aim of this thesis was to identify potential liquid biopsy based diagnostic biomarkers, and investigate whether they are suitable for clinical implementation and use for the early detection of recurrent or residual HNSCC in order to improve the overall survival and quality of life of HNSCC patients in the future. In this respect, this thesis has contributed to the fast growing field of liquid biopsy in HNSCC patients by exploring a wide variety of (pre)clinical aspects, and thereby paved the road for further, more focused research on ctDNA analysis in HNSCC patients. Although several of these aspects remain unclear, this thesis provides a lead for further investigating the use of liquid biopsies for personalized head and neck cancer management in order to improve patient disease outcome and quality of life ultimately.