{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:38:02Z","timestamp":1785523082504,"version":"3.56.0"},"reference-count":204,"publisher":"MDPI AG","issue":"7","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":["Cancers"],"abstract":"<jats:p>Cellular senescence is a stress-induced state characterised by durable proliferative arrest and extensive transcriptional and secretory reprogramming. In cancer, senescence can suppress early tumour outgrowth, yet persistence of senescent cells and their senescence-associated secretory phenotype (SASP) may drive maladaptive inflammation, immune dysfunction, vascular perturbation and extracellular matrix (ECM) remodelling. Head and neck squamous cell carcinoma (HNSCC) provides a clinically informative context because tumours arise in injury-prone mucosa and standard therapies (radiotherapy and platinum-based chemotherapy) can induce long-lived senescent phenotypes across stromal and vascular compartments. Here, we synthesise the evidence through a signal \u2192 matrix \u2192 function framework, in which the therapy-induced SASP modules reshape collagen density, alignment, confinement and crosslinking, thereby influencing invasion, immune access, perfusion and post-treatment fibrosis. We emphasise that senescence detection in head and neck tissues is highly context-dependent and readily confounded by inflammageing, chronic mucosal injury and HPV-associated biology, necessitating a cell-type-resolved, spatially anchored, multi-axis definition that integrates growth-arrest context, nuclear\/DNA damage response hallmarks and functional outputs. We highlight oral submucous fibrosis (OSF) as a matrix-primed precursor state that exemplifies convergence between chronic injury, fibrosis and senescence-adjacent programmes. Finally, we propose an integrated translational roadmap combining multiplex spatial pathology with quantitative collagen imaging to map therapy-induced senescence\u2013ECM niches and support biomarker-guided testing of senomorphic, senolytic and matrix-normalising strategies in HNSCC.<\/jats:p>","DOI":"10.3390\/cancers18071126","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"1126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapy-Induced Senescence Shapes Extracellular Matrix Niches and Fibroblast Function in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6298-4830","authenticated-orcid":false,"given":"Jetsy","family":"Montero-Vergara","sequence":"first","affiliation":[{"name":"The Liverpool Head & Neck Centre, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6339-4260","authenticated-orcid":false,"given":"Piotr W.","family":"Darski","sequence":"additional","affiliation":[{"name":"The Liverpool Head & Neck Centre, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-9338","authenticated-orcid":false,"given":"Amy L.","family":"Harding","sequence":"additional","affiliation":[{"name":"The Liverpool Head & Neck Centre, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7873-0877","authenticated-orcid":false,"given":"Keith D.","family":"Hunter","sequence":"additional","affiliation":[{"name":"The Liverpool Head & Neck Centre, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of Cellular Senescence","volume":"28","author":"Nehme","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: When bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. 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