Tumor DNA: an emerging biomarker in head and neck cancer

Abstract

Head and neck cancer (HNC) includes a diverse range of malignancies arising commonly from mucosal epithelia of the upper aerodigestive tract. Head and neck squamous cell carcinoma (HNSCC), the most common form of HNC, develops in the oral cavity, pharynx, and larynx and is associated with tobacco exposure, alcohol abuse, and infection with oncogenic viruses. Despite global advances in cancer care, HNSCC often presents with advanced disease and is associated with poor 5-year survival of ~50%. Genotyping tumor tissue to guide clinical decision-making is becoming commonplace in modern oncology, but in the management of HNSCC, tissue biopsies with cytopathology or histopathology remain the mainstay for diagnosis. Furthermore, conventional biopsies are temporally and spatially limited, often providing a brief snapshot of a single region of a heterogeneous tumor. In the absence of a useful biomarker, both primary and recurrent HNSCCs are diagnosed with conventional imaging and clinical examination. As a result, many patients are diagnosed with advanced disease. Tumor DNA is an emerging biomarker in HNSCC. DNA fragments are constantly being shed from tumors and metastatic lesions, and can therefore be detected in blood and other bodily fluids. Utilizing next-generation sequencing techniques, these tumor DNA can be characterized and quantified. This can serve as a minimally invasive liquid biopsy allowing for specific tumor profiling, dynamic tumor burden monitoring, and active surveillance for disease recurrences. In HNSCC, analysis of tumor DNA has the potential to enhance tumor profiling, aid in determining patient prognosis, and guide treatment decisions.

Keywords: Cancer genetics; Circulating tumor DNA; Head and neck cancer; Liquid biopsy.

Fig. 1

Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Adapted from Bettegowda et al. (2014) [45]. Reprinted with permission from AAAS. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and HPVDNA into the saliva or the circulation

Fig. 2

Proposed applications of tumor DNA as a biomarker for HNSCC. ctDNA collected from patient plasma and saliva could aid clinicians in earlier diagnosis of HNSCC and serve as a valuable marker of tumor burden to monitor for response to treatment and disease recurrence