Search Results (1,876)

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with particular emphasis on oral cancer. We integrate the available evidence to assess the biological rationale, therapeutic potential, and current limitations of curcumin-based approaches. The molecular mechanisms underlying their antitumor activity are discussed, including modulation of EGFR/ERK and PI3K/Akt signaling pathways, inhibition of NF-κB and STAT3 activation, induction of apoptosis, regulation of oxidative stress, and suppression of epithelial–mesenchymal transition and tumor invasiveness. In addition, we address the impact of curcumin on the tumor microenvironment and its role in overcoming intrinsic cellular resistance mechanisms. The review also highlights advances in drug delivery strategies, such as nanoformulations, that are designed to improve curcumin’s bioavailability and therapeutic efficacy. By critically integrating current evidence, this review highlights both the promise and the challenges associated with curcumin-based monotherapy in HNC, emphasizing the need for more robust and clinically relevant studies to support future translation. Full article

Radiotherapy is central to the treatment of nasopharyngeal carcinoma and selected sinonasal malignancies, but sinonasal toxicity remains incompletely characterized. Radiation-induced rhinosinusitis (RIR) is increasingly recognized after head-and-neck radiotherapy, particularly in nasopharyngeal carcinoma, where the paranasal sinuses and drainage pathways may receive substantial incidental dose. Reported prevalence varies widely because studies use different endpoints, including radiologic mucosal thickening, endoscopic inflammation, and patient-reported symptoms. Across available nasopharyngeal carcinoma cohorts, imaging-defined sinonasal inflammatory changes are common, with reported rates generally ranging from approximately 30% to more than 70% depending on timing, radiation technique, and diagnostic criteria. This narrative review summarizes current evidence on the epidemiology, pathophysiology, dosimetric predictors, imaging findings, prevention, and management of RIR. Radiation-induced sinonasal injury appears to arise from epithelial damage, impaired mucociliary clearance, altered local defense, and chronic mucosal remodeling. Available data suggest that higher doses to the paranasal sinuses and drainage pathways, baseline sinus disease, and tumor extension into sinonasal structures increase risk, although validated dose constraints are not yet established. We propose a harmonized reporting framework that integrates symptoms, endoscopy, imaging, dosimetry, baseline sinonasal status, and oncologic context. Greater recognition of RIR as a clinically meaningful survivorship toxicity may support more consistent outcome reporting, prospective studies, and future radiation-planning strategies aimed at reducing sinonasal morbidity. Full article

Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive and heterogeneous malignancies worldwide, characterized by high rates of locoregional recurrence, metastatic dissemination, and therapeutic resistance. Angiogenesis plays a central role in tumor progression by supporting vascular remodeling, hypoxia adaptation, invasion, immune evasion, and metastatic spread. In HNSCC, angiogenic activation is regulated through complex interactions involving hypoxia-inducible factors, vascular endothelial growth factor (VEGF) signaling, stromal remodeling, inflammatory pathways, and epigenetic mechanisms within the tumor microenvironment. Recent evidence has also highlighted the role of non-coding RNAs, particularly microRNAs, and exosome-mediated communication in modulating angiogenic and immune-related signaling pathways. Although antiangiogenic therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated biological activity in HNSCC, their clinical efficacy remains limited by tumor heterogeneity, adaptive resistance mechanisms, toxicity, and the lack of validated predictive biomarkers. Several emerging therapeutic strategies are under preclinical or early clinical investigation in HNSCC, including miRNA-based approaches, nanoparticle-assisted delivery systems, vascular normalization concepts, and combinations with immune checkpoint inhibitors; however, robust clinical evidence for most of these strategies remains limited, and their translation to routine practice requires further validation. This review provides a comprehensive overview of the molecular mechanisms regulating angiogenesis in HNSCC and critically discusses current and emerging pharmacological strategies targeting these pathways. Particular emphasis is placed on VEGF/VEGFR signaling, the integration of miRNA and exosome biology, resistance mechanisms, and translational perspectives for biomarker-guided personalized therapy. The novelty of this review lies in the systematic integration of miRNA- and exosome-mediated angiogenic regulation, therapeutic resistance pathways, and precision medicine strategies into a unified pharmacological framework, addressing gaps not fully covered by prior reviews focused primarily on VEGF-targeted agents. Full article

Background: Spread through air spaces (STAS) is a recognized histologic pattern of invasion associated with poor prognosis in non-small-cell lung cancer (NSCLC), particularly adenocarcinoma. However, its presence in pulmonary squamous cell carcinoma (SCC), whether primary or metastatic, remains largely unexplored. Given the limited available evidence, this study was designed as an exploratory analysis to evaluate the prevalence and potential prognostic significance of STAS in pulmonary SCC. Material and Methods: In this exploratory retrospective study, we analyzed 57 patients who underwent surgical resection for pulmonary squamous cell carcinoma (P-SCC) at the Department of Thoracic Surgery at the University Hospital Erlangen between 2008 and 2020. The cohort included both primary lung SCC and metastatic SCC to the lung from extrapulmonary sites, primarily from ear, nose, and throat (ENT) tumors. Histological slides were reviewed to assess the presence of STAS, as defined by established morphological criteria. The Chi-square test was used to investigate the presence of STAS. Disease-free survival (DFS) and overall survival (OS) was evaluated using Kaplan–Meier analysis, and the prognostic impact of STAS along other variables were assessed using Cox proportional hazards regression. Results: A total of 57 patients with squamous cell carcinoma (SCC), 22 (39%) had primary lung SCC and 35 (61%) had metastatic SCC from head and neck tumours (ENT). Spread through air spaces (STAS) was detected in 20 patients (35%). Disease-free survival (DFS) differed according to primary tumour location (p-value of 0.009), with higher 1-, 3-, and 5-year DFS in patients with primary lung SCC (86.4%, 77.3%, 63.3%) than in those with head and neck SCC (54.3%, 31.4%, 22.2%). DFS was also significantly higher in patients undergoing solitary resections compared with multiple resections (78.6%, 64.3%, 49.5% vs. 33.3%, 6.7%, not estimable; p-value < 0.001). DFS was slightly longer in STAS-negative patients compared with STAS-positive patients (1-, 3-, 5-year DFS: 64.9%, 51.4%, 40.5% vs. 70%, 45%, not estimable), (median DFS 36 vs. 25 months; p-value of 0.776). Overall survival (OS) was significantly longer in patients with primary lung SCC (median OS 125 months) than in those with head and neck SCC (27 months; p-value of 0.039). STAS-negative patients had also a longer OS than STAS-positive patients (median OS 46 vs. 38 months; HR = 1.11, 95% CI 0.56–2.20; p-value of 0.771). Conclusions: STAS was identified in metastatic pulmonary SCC lesions as well as in primary lung SCC, occurring in approximately one-third of cases. However, due to the limited cohort size and the exploratory univariate design of the study, the prognostic significance of STAS could not be definitively established and requires further investigation in larger, adequately powered studies. Full article

Chemoradiotherapy plays an important role in the management of locally advanced head and neck squamous cell carcinoma. Unfortunately, a substantial fraction of patients experience treatment failure, while others suffer from significant treatment-related toxicity caused by intensive chemoradiotherapy regimens. This underscores the need for new biomarkers that can accurately capture the biological tumor heterogeneity and guide personalized therapy. Functional imaging combined with AI-based approaches such as radiomics and deep learning may offer a promising strategy for treatment stratification. However, a substantial number of challenges remain before clinical implementation can be achieved. Therefore, this review proposes a biology-driven framework for AI analysis of functional imaging in head and neck squamous cell carcinoma. In addition, it emphasizes the need for clinically oriented validation strategies to facilitate the translation of stratification models into clinical management. Full article

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with a high risk of recurrence. While adjuvant radiotherapy is standard following surgical resection in high-risk disease, the additional benefit of platinum–etoposide chemotherapy and the prognostic role of tumor anatomical location remain uncertain. Methods: We conducted a multicenter retrospective cohort study including patients with high-risk MCC (stage IIB–III) treated with surgery followed by adjuvant radiotherapy with or without platinum–etoposide chemotherapy. Tumor sites were classified according to sun-exposure status. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using the log-rank test, with subgroup analyses by anatomical region and stage. Results: A total of 103 patients were included, of whom 77 (74.8%) received adjuvant chemoradiotherapy and 26 (25.2%) received radiotherapy alone. Patients with non-sun-exposed tumors demonstrated longer survival outcomes than those with sun-exposed tumors, with a median DFS of 57 months versus 42 months (p = 0.15), and a median OS of 179 months versus 109 months (p = 0.054), respectively. Among patients with sun-exposed tumors, chemoradiotherapy was associated with numerically improved DFS (42 vs. 34 months; p = 0.051) and OS (128 vs. 98 months; p = 0.08) compared with radiotherapy alone. In patients with non-sun-exposed tumors, chemoradiotherapy demonstrated a more pronounced improvement in OS (178 vs. 56 months; p = 0.054), while DFS also favored combined treatment (49 vs. 78 months; p = 0.078). Conclusions: In this multicenter cohort, adjuvant chemotherapy did not demonstrate a uniform survival benefit overall but was associated with improved outcomes in head and neck MCC, suggesting a potential site-specific effect. Similar outcomes across stage III subgroups suggest that chemotherapy may mitigate stage-related prognostic differences. These findings support a selective approach to adjuvant chemotherapy and highlight the need for prospective studies incorporating modern immunotherapy strategies. Full article

Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article

Background/Objectives: Intraoperative fluorescence imaging (FI) with tumor-targeted tracers offers a promising approach to improve surgical precision in cancer surgery. cRGD-ZW800-1, an integrin-targeted fluorescent tracer, has previously demonstrated safety, tumor specificity, and utility in detecting inadequate margins in oral cancer. During this study, we observed variability in background fluorescence between different subsites of the oral cavity. Therefore, this study aimed to systematically evaluate intraoperative in vivo and ex vivo mucosal contrast ratios across various oral cavity subsites using FI with cRGD-ZW800-1. Methods: Thirty-one patients with oral squamous cell carcinoma underwent intraoperative FI following intravenous injection of cRGD-ZW800-1 at least 18 h preoperatively. In vivo imaging was performed using the Quest Spectrum platform. In addition, ex vivo FI of the resected specimen was performed using the Pearl Trilogy Small Animal Imaging System. As these ex vivo images were obtained under uniform and controlled acquisition conditions, they allow for direct comparison with the intraoperative fluorescence signals. Fluorescence intensities and tumor-to-background ratios (TBRs) were assessed per oral subsite using manually drawn regions of interest (ROIs) on the tumor and adjacent healthy mucosa using Quest’s Spectrum Software, version 4.8.2, (in vivo images) and the Pearl’s integrated software ImageStudio version 6.2 (ex vivo images). A TBR ≥ 1.5 was considered sufficient. Results: Under uniform imaging settings, all samples exhibited adequate contrast (TBR ≥ 2.3), allowing clear tumor visualization and precise evaluation of mucosal margins on final histopathology. Notably, intraoperative in vivo contrast in the posterior located maxillary alveolar process was comparatively lower, which was attributable to suboptimal imaging conditions and subsite-specific background fluorescence. Conclusions: Our findings indicate that, although contrast varies across different oral subsites, all specimens exhibited sufficient ex vivo mucosal contrast to allow reliable tumor delineation. As in vivo imaging may be affected by subsite-specific background fluorescence and inherent limitations of intraoperative imaging geometry, fluorescence signals should be interpreted in conjunction with standard visual and tactile assessment. Due to anatomical constraints, different oral subsites may appear within the same field of view, which can influence perceived signal intensity. Therefore, intraoperative ex vivo fluorescence evaluation is recommended for signal interpretation. Full article

5-Aminolevulinic acid (5-ALA) has emerged as an important theranostic agent in oncology due to its selective intracellular conversion to protoporphyrin IX (PpIX), enabling both photodynamic diagnosis (PDD) and photodynamic therapy (PDT). This narrative review summarizes current knowledge regarding the biological mechanisms underlying 5-ALA metabolism, selective tumor accumulation, and the clinical applications of 5-ALA-based approaches across multiple oncological indications. Particular emphasis is placed on glioblastoma, head and neck lesions, dermatological malignancies, urological cancers, gynecological lesions, and emerging translational applications. The review also discusses key biological and technical limitations, including tumor hypoxia, restricted light penetration, heterogeneous PpIX accumulation, resistance mechanisms, and tumor-specific variability. Recent advances in drug delivery systems, nanotechnology, sonodynamic therapy, radiodynamic strategies, and combination immunotherapeutic approaches are also highlighted. Collectively, current evidence indicates that while 5-ALA has established clinical utility in selected indications, many applications remain preclinical or early translational, underscoring the need for further well-designed clinical studies. Full article

Background: Buparlisib, combined with paclitaxel, improved survival in BERIL-1 trial patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, predictive biomarkers of benefit remain undefined. Objective: To evaluate whether spatial biomarkers extracted from hematoxylin and eosin (H&E) slides using artificial intelligence (AI) can predict overall survival benefit from buparlisib. Methods: Whole-slide H&E images from BERIL-1 trial patients were analyzed using a deep learning model trained to segment tissue compartments and classify cell phenotypes. Three predefined spatial features were evaluated: tumor-infiltrating lymphocyte density, tumor microenvironment heterogeneity, and granulocyte fraction in the tumor invasive margin. Cox proportional hazards model assessed biomarker-treatment interactions. Results: Of 158 trial participants, 144 had available slides. High tumor-infiltrating lymphocyte density (>10%) was associated with significantly improved overall survival with buparlisib versus placebo (HR, 0.25 (95% CI, 0.01–0.64; p = 0.002)), as were high tumor microenvironment heterogeneity (HR, 0.47 (95% CI, 0.27–0.80; p = 0.005)) and granulocyte enrichment in the tumor invasive margin (HR, 0.51 (95% CI, 0.30–0.88; p = 0.01)); within-arm proximity analysis showed higher granulocyte–tumor-cell proximity correlated with improved overall survival on buparlisib (HR, 0.32 (95% CI, 0.18–0.58; p < 0.001)). AI-derived spatial metrics outperformed CD3 immunohistochemistry. Among oropharyngeal tumors, HPV-positive cases were more frequent in patients with high tumor-infiltrating lymphocytes. Conclusions: AI-extracted spatial features from H&E slides were associated with overall survival benefit from buparlisib in R/M HNSCC. These scalable biomarkers support image-based patient selection strategies and are being prospectively evaluated in the BURAN phase 3 trial. Full article

Background: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine neoplasms that may be sporadic or hereditary and may occur as isolated, multifocal, or syndromic disease within the pheochromocytoma-paraganglioma spectrum. Synchronous bilateral carotid body tumors (CBTs) and bilateral vagal paragangliomas (VPGLs) are exceptional, particularly when biochemical activity and metastatic nodal involvement coexist. Case Presentation: We report a 33-year-old man with a 2-year history of enlarging bilateral neck masses, positive family history, and markedly elevated noradrenaline (6430 pg/mL; reference range <750 pg/mL). Initial CT angiography suggested bilateral CBTs, and Metaiodobenzylguanidine (MIBG) scintigraphy did not demonstrate abnormal adrenal or distant uptake. After alpha- and beta-blockade, staged surgery was performed. Right CBT excision demonstrated metastatic PGL, with two of four lymph nodes positive. Subsequent MRI and operative reassessment revealed synchronous bilateral CBTs and bilateral VPGLs. Left-sided surgery required partial debulking of a vagal-adherent mass to preserve nerve continuity; pathology confirmed PGL with Ki-67 index approximately 2% and left neck nodes were negative. Postoperatively, profound bradycardia required temporary then permanent pacing, together with bilateral vocal cord paralysis. During follow-up, swallowing and voice improved, the pacemaker was removed, and late imaging showed stable residual cervical disease without visceral metastasis on chest/abdominal CT. Conclusions: This case highlights the diagnostic and therapeutic complexity of multicentric, biochemically active HNPGLs and supports individualized multidisciplinary management, genetic counseling, biochemical surveillance, and long-term follow-up. Full article

Background: Perioperative immunotherapy has emerged as a promising strategy for improving outcomes in patients with resectable head and neck squamous cell carcinoma (HNSCC). However, its biological rationale, clinical evidence, and optimal implementation remain incompletely defined. Methods: We conducted a narrative review of the current literature, integrating preclinical and clinical evidence on perioperative immune checkpoint inhibitor (ICI) therapy in resectable HNSCC, with particular attention to the immunological impact of surgery, tumor-draining lymph nodes, and treatment sequencing. Results: Neoadjuvant immunotherapy exploits the presence of intact tumor antigen and preserved lymphatic architecture, enabling broad T-cell priming, clonal expansion, and systemic immune memory formation. In contrast, adjuvant immunotherapy primarily targets residual microscopic disease and relies on preexisting tumor-reactive T cells, suggesting that these strategies are biologically distinct. Early-phase clinical trials have demonstrated the safety and feasibility of perioperative ICIs, with evidence of pathological responses. Recent phase III trials, including KEYNOTE-689 and NIVOPOSTOP, have provided practice-relevant evidence supporting the integration of ICIs into perioperative treatment, demonstrating improved event-free survival and clinical outcomes in selected populations. Several challenges remain, including optimal patient selection, lack of validated biomarkers, and treatment sequencing after perioperative ICI exposure. Conclusions: Perioperative immunotherapy represents a promising practice-relevant strategy in resectable HNSCC. Further studies are required to refine patient selection, develop predictive biomarkers, and optimize treatment sequencing to maximize clinical benefit. Full article

Background and Clinical Significance: SWI/SNF chromatin remodeling complex-deficient malignancies constitute an aggressive group of undifferentiated tumors defined by inactivation of core subunits including SMARCA4 (BRG1) or SMARCB1 (INI1). In the head and neck, these tumors predominate in the sinonasal tract; oral cavity presentations are exceedingly rare, with reported cases predominantly representing metastatic disease. Peri-implant gingival masses in clinical practice are overwhelmingly reactive, but their occasional malignant nature mandates timely biopsy and thorough pathologic workup. We report the first comprehensively molecularly characterized case of a peri-implant gingival SWI/SNF complex-deficient tumor with confirmed biallelic SMARCA4 inactivation. Case Presentation: A 75-year-old man presented with a one-week history of a rapidly enlarging exophytic erythematous peri-implant gingival mass in the right posterior mandible (region 44–47). Incisional biopsy demonstrated an undifferentiated high-grade tumor with epithelioid, plasmablastoid, and focally rhabdoid morphology with necrosis. Immunohistochemistry showed complete loss of BRG1 (SMARCA4) with retained INI1 (SMARCB1), EMA positivity, Ki-67 of approximately 100%, and negativity across all lineage-specific markers (hematolymphoid, epithelial, melanocytic, endothelial, squamous). Comprehensive next-generation sequencing (Oncomine Comprehensive Assay Plus) confirmed biallelic SMARCA4 inactivation via a truncating nonsense mutation (p.Trp1346Ter; VAF 73.85%) combined with copy number loss, establishing the molecular mechanism underlying BRG1 protein loss. Co-occurring alterations included homozygous CDKN2A/CDKN2B deletion, MTAP loss (9p21.3), clonal TP53 and KEAP1 mutations, and intermediate–high tumor mutational burden (13.3 mutations/Mb) with microsatellite stability. The patient initiated carboplatin–paclitaxel and achieved a partial response at one month with further shrinkage by four months. This case illustrates a rare oral cavity manifestation of SWI/SNF complex deficiency arising in a peri-implant location, with a diagnostic workup that required integration of immunohistochemistry and molecular profiling for definitive characterization. The MTAP deletion co-occurring with homozygous CDKN2A/B loss identifies a potentially actionable synthetic lethal vulnerability to MAT2A and PRMT5 inhibitors currently under clinical investigation. An occult primary site could not be fully excluded due to absence of a dedicated staging workup. Conclusions: Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class. Full article

Human papillomaviruses (HPVs) comprise more than 200 types associated with diverse clinical outcomes, ranging from benign lesions caused by low-risk types to cancers driven by high-risk types. These differences are partly driven by variation in the Long Control Region (LCR), a non-coding element that regulates viral gene expression through interactions with viral and host transcription factors (TFs). Although individual TF binding sites have been mapped in a few well-studied HPV types, the broader regulatory differences between high-risk and low-risk HPVs remain poorly defined. Here, we systematically analyzed LCR sequences from 207 HPV types using TF motif scanning and identified 104 TFs with significantly different binding site densities between risk groups. Integration with TCGA transcriptomics data showed that 50 of 69 TF enriched in high-risk types are expressed in HPV-positive head and neck tumors (HNSC) and 53 in HPV-positive cervical tumors (CESC). Analysis of published ChIP-seq datasets further confirmed LCR occupancy for seven of these TFs in HPV18-positive cells. In addition, conservation analysis across clinical isolates of HPV-16 and HPV-18 identified highly conserved TF binding sites overlapping multiple high-risk-enriched TF motifs, suggesting functional constraint on key regulatory elements. Together, these findings reveal distinct TF binding landscapes associated with HPV risk groups and identify candidate host regulators that may contribute to differences in viral transcriptional programs and oncogenic potential across HPV types. Full article

Background and Objectives: Head and neck cancers are heterogeneous malignancies with variable biological behavior and treatment response, contributing to high morbidity and mortality. Conventional imaging techniques are limited in their ability to capture tumor biology, highlighting the need for advanced functional imaging. This review aims to evaluate the role of multiparametric magnetic resonance imaging (MRI) in characterizing the tumor microenvironment. Materials and Methods: A narrative review was conducted based on a targeted literature search of databases, including PubMed and Google Scholar. Studies addressing advanced MRI techniques for assessing tumor cellularity, vascularity, molecular features, and oxygenation were selected and analyzed. Results: Perfusion techniques, such as dynamic contrast-enhanced MRI (DCE-MRI) and arterial spin labeling (ASL), provide a quantitative assessment of tumor vascularity and show value in predicting treatment response. Diffusion-based methods, including diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), enable evaluation of tissue cellularity and heterogeneity. Molecular approaches, such as chemical exchange saturation transfer (CEST) and amide proton transfer (APT), offer insights into protein content and proliferation. Oxygenation-sensitive techniques, such as blood oxygenation level dependent MRI (BOLD MRI) and oxygen-enhanced MRI (OE-MRI), allow non-invasive assessment of tumor hypoxia. Conclusions: Multiparametric MRI provides a comprehensive and biologically relevant evaluation of the tumor microenvironment in head and neck cancer, with potential to improve treatment prediction and support personalized therapeutic strategies. Full article