Enhanced glycolysis and nicotinamide metabolism in HPV-positive head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally, with increasing prevalence driven largely by human papillomavirus (HPV) infection. Current standard therapies frequently leave patients with severe, long-term functional impairments, significantly reducing quality of life. Although HPV-positive HNSCC has improved prognosis and better treatment responses compared to HPV-negative disease, the underlying metabolic distinctions remain poorly defined. Using comprehensive metabolomic profiling via ultra-performance liquid chromatography-mass spectrometry in well-established HPV-positive (SCC47, SCC104) and HPV-negative (Detroit562, SCC9) HNSCC cell lines, we demonstrate for the first time through comprehensive metabolomic analysis that HPV-positive HNSCC uniquely enhances metabolic pathways advantageous for rapid cell proliferation, including glycolysis and nicotinamide metabolism. Conversely, HPV-negative HNSCC primarily relies on downstream components of the tricarboxylic acid cycle for energy production. Identifying these differential metabolic has important implications for precision-oncology in the development of targeted therapeutics for HPV-positive HNSCC patients.