{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:31:55Z","timestamp":1789659115691,"version":"4.0.1"},"reference-count":171,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Head and neck squamous cell carcinoma (HNSCC) continues to pose a major global health challenge, with over 600,000 new cases diagnosed annually and persistently poor survival outcomes despite advances in surgery, radiotherapy, and immunotherapy. Growing evidence implicates metabolic reprogramming, including enhanced glycolysis, glutaminolysis, lipid synthesis, and one-carbon\/redox flux as a central driver of HNC initiation, progression, and therapy resistance. In contrast, metabolic crosstalk within the hypoxic, acidic tumor microenvironment (TME) further shapes immune evasion and stromal support. Recent innovations in mass spectrometry platforms (LC-MS, GC-MS, NMR) have attracted attention in clinical therapeutics, and spatial metabolomics imaging techniques now enable high-resolution in situ mapping of metabolites, revealing intratumoral heterogeneity and offering new insights into tumor-immune\u2013stromal interactions and potential biomarkers for precision oncology. In this review, we integrate critical methodological considerations from sample collection and data-analysis workflows to analytical pitfalls with a balanced, pathway-focused analysis of HNSCC dysmetabolism, examine tumor immune stromal metabolic interactions, and highlight translational opportunities through emerging biomarkers, targeted inhibitors, and cutting-edge approaches such as single-cell and AI-driven metabolomics to chart a roadmap toward precision oncology for HNSCC.<\/jats:p>","DOI":"10.3390\/curroncol33040201","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolomic Insights into Head and Neck Cancer: Recent Advances and Future Directions"],"prefix":"10.3390","volume":"33","author":[{"given":"Srikanth","family":"Ponneganti","sequence":"first","affiliation":[{"name":"Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3213-3938","authenticated-orcid":false,"given":"Kousalya","family":"Lavudi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-6929","authenticated-orcid":false,"given":"Maharshi","family":"Thalla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatri","family":"Narkhede","sequence":"additional","affiliation":[{"name":"Biocon Bristol Myers Squibb Research & Development Center, Bengaluru 560099, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reva","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-2629","authenticated-orcid":false,"given":"Rekha","family":"Kokkanti","sequence":"additional","affiliation":[{"name":"School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-914X","authenticated-orcid":false,"given":"Prashant","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, Uttar Pradesh, India"},{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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