Search Results (167)

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant potential in curbing tumor cell proliferation and slowing tumor expansion. However, its specific effects on cell senescence within the context of OSCC have remained shrouded in uncertainty. This study delves into the mechanisms of EVO’s impact on OSCC by harnessing databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and CellAge to pinpoint potential targets and carry out in-depth bioinformatics analysis. The findings reveal that EVO can markedly enhance the expression of the androgen receptor (AR) in OSCC cells, inducing cellular senescence and thereby inhibiting tumor progression. Furthermore, the research indicates that AR expression is considerably lower in OSCC tissues than in normal tissues. This low expression of AR in tumor tissues is closely associated with advanced clinical stages and unfavorable prognoses in HNSCC patients. These discoveries open up new avenues for therapeutic strategies, and suggest that AR holds promise as a potential therapeutic target for OSCC, and EVO may amplify its antitumor effects by enhancing AR-mediated cellular senescence in the treatment of OSCC. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer, with limited responsiveness to immune checkpoint inhibitors (ICIs). Cancer vaccine therapy is a promising novel immunotherapeutic approach that stimulates tumor-specific T cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is overexpressed in malignant tumors but minimally expressed in normal tissues, presents a promising target for immunotherapy. This study aimed to evaluate ROR1 as a target for helper T lymphocyte (HTL)-based peptide vaccine immunotherapy in HNSCC. Methods: ROR1 expression in HNSCC tissues was assessed by immunohistochemistry. A novel ROR1-derived epitope (ROR1_403–417) was identified and used to generate ROR1-reactive HTLs. Functional assays measuring IFN-γ and granzyme B secretion, as well as direct cytotoxicity, were performed. The effects of ICIs on HTL activity were also examined. The presence of ROR1-reactive T cells in the peripheral blood of patients with HNSCC was evaluated. Results: ROR1 positivity rates in HNSCC tissues were significantly higher (80.0%) than those in healthy controls (16.7%), and high ROR1 expression correlated with advanced clinical stages. HTL lines recognized the ROR1_403–417 peptide in a human leukocyte antigen (HLA)-DR-restricted manner, secreted effector cytokines, and exhibited direct cytotoxicity against ROR1+ tumor cells. Dual PD-L1/PD-L2 blockade further enhanced HTL responses. ROR1-reactive T cells were detected in the peripheral blood of patients with HNSCC. Conclusions: ROR1 represents a promising target for immunotherapy in HNSCC. The ROR1_403–417 peptide can elicit ROR1-reactive HTLs that exhibit antitumor responses against HNSCC cell lines, which can be enhanced by ICIs. These findings support the potential of ROR1-targeted peptide vaccine therapy for HNSCC. Full article

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive cancer, and accurate staging using the AJCC system is essential for treatment planning. This study aims to enhance AJCC staging by integrating both clinical and imaging data using a multimodal deep learning pipeline. We propose a framework that employs a VGG16-based masked autoencoder (MAE) for self-supervised visual feature learning, enhanced by attention mechanisms (CBAM and BAM), and fuses image and clinical features using an attention-weighted fusion network. The models, benchmarked on the HNSCC and HN1 datasets, achieved approximately 80% accuracy (four classes) and ~66% accuracy (five classes), with notable AUC improvements, especially under BAM. The integration of clinical features significantly enhances stage-classification performance, setting a precedent for robust multimodal pipelines in radiomics-based oncology applications. Full article

Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth in incidence and seventh in cancer mortality worldwide. Approximately 30% of HNSCC cases are related to human papillomavirus (HPV) infection, the oropharynx being the anatomical subsite most associated with HPV infection. Traditionally, HPV-positive HNSCC has been considered to have better treatment response and clinical outcome. However, HPV-positive HNSCC is a heterogeneous group since 30% of the cases present early relapse, which implies that there are differences in molecular profiles within HPV-positive patients. In this study, we used bioinformatic data analysis from open-access repositories to compare molecular profiles differentially expressed between HPV-positive and -negative HNSCC patients. Using the TCGA HNSCC transcriptomic data, we identified a group of genes, whose expression is related to clinical outcome in patients. Our findings were validated in an independent cohort confirming that the expression levels of FABP4, HMGA2, S100A10, GDNF, SLC7A,2 and GPR18 genes were associated with overall survival (OS) exclusively in HPV-positive HNSCC patients, while ST6GALNAC1 expression was associated with OS in HPV-negative HNSCC. The expression of OS-related genes was independent of tumor stage and history of alcoholism. Our findings suggest that transcriptional profiles in HPV-positive HNSCC are an excellent source of information for the search for potential prognostic biomarkers. Full article

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of OSCC diagnosis and treatment. This review provides a comprehensive synthesis of early molecular diagnostic strategies, including biomarker discovery using next-generation sequencing, liquid biopsy, and salivary exosomal microRNAs. In addition, we highlight the emerging role of non-invasive optical imaging technologies and their clinical integration for improved surgical precision and early lesion detection. This review also discusses evolving therapeutic approaches, including immunotherapy, neoadjuvant chemotherapy, and patient-centered multimodal regimens tailored through molecular profiling. We emphasized balancing therapeutic efficacy with the quality of life in patients undergoing chemoradiotherapy. The convergence of multi-omics, artificial intelligence, and precision medicine holds promise for revolutionizing early detection and personalized treatment of OSCC, ultimately improving patient survival and clinical outcomes. Full article

Background/Objectives: The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage treatment. Methods: This retrospective study examines the impact of implementing a structured initial restaging between three and six months after the conclusion of initial treatment. The study population included 532 patients treated with curative intent at the University Medicine of Greifswald, Germany, between 2010 and 2019. Patients were divided into two groups: standard follow-up (SF) and adapted follow-up (AF). The AF group received standardized post-treatment restaging, including imaging and panendoscopy or PET-CT exams. Results: We found a trend towards earlier diagnosis and a reduction in recurrences, although these differences were not statistically significant. Secondary cancers were observed more frequently in the AF group, significantly affecting overall survival. Conclusions: Our cohort supports structured initial cancer follow-up in HNSCC. Although not significant, an initial multimodal exam after treatment was well tolerated and showed a trend toward earlier diagnosis. Full article

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis. Full article

Objective: In Mexico, head and neck cancers pose a significant health burden. GLOBOCAN reported approximately 3183 new cases and 1636 deaths in 2020. Despite being the sixth leading cause of cancer incidence and mortality worldwide, data on epidemiology and treatment patterns in Mexico remain limited. This study aimed to characterize the profile, clinical features, and management of patients with Stage III–IVB head and neck squamous cell carcinoma (HNSCC) in a real-world setting. Methods: We retrospectively analyzed a database of 187 patients with Stage III, IVA, or IVB HNSCC treated at the University Hospital Dr. José Eleuterio González. Demographics, disease characteristics, and treatment patterns were summarized as frequencies and percentages. Exploratory endpoints included clinical outcomes and recurrence types. Results: The cohort was 82.9% male (n = 155). The most frequent tumor sites were the oral cavity (36.9%) and larynx (36.9%), with 55% (n = 103) diagnosed at stage IVA. Of 75 cases tested for p16, 35.3% (n = 36) were positive. The median time from symptom onset to diagnosis was 166.5 days (95% CI: 123.4–197.8) and from diagnosis to treatment 42 days (95% CI: 31.6–50.4). Initial treatments included surgery (36.4%), chemoradiotherapy (24.6%), induction chemotherapy (19.8%), supportive care (11.2%), and radiotherapy (8%). Locoregional control was achieved in 42.8% of patients, with an overall recurrence rate of 2.8%. Conclusions: This study provides real-world insights into the epidemiology and management of locally advanced HNSCC in Mexico, outlining the patient journey from initial symptoms to treatment and underscoring the need for more individualized therapeutic strategies based on molecular profiling and clinical characteristics. Full article

Head and neck squamous-cell carcinoma (HNSCC) has long been associated with tobacco and alcohol use. In the last two decades, however, human papillomavirus (HPV) infection has emerged as an important driver of these cancers, particularly in the oropharynx. The eighth edition of the American Joint Committee on Cancer (AJCC) staging system now defines HPV+ and HPV− OPSCC as separate entities. Although our understanding of HPV+ HNSCC continues to improve, it can be challenging to keep up to date with the growing body of evidence. In this context, the present narrative review was carried out to provide an overview of HPV-driven head and neck cancer, with an emphasis on Europe. We review the latest evidence on epidemiology, diagnosis, and treatment, including recent trends towards treatment de-intensification and future directions. Full article

The detection of circulating tumor cells (CTCs) using immunoaffinity-based methods often relies on epithelial-related markers, which may bias the selection of CTCs and limit the biological information obtained, depending on the targeted antigens. Herein, we compared the molecular profiles and clinical significance of CTCs based on the expression of epithelial-related markers (EPCAM, EGFR, and MET) in patients with head and neck squamous-cell carcinoma (HNSCC). CTCs were detected using density gradient separation and CD45-negative selection, followed by quantitative PCR for epithelial-related marker expression. Expression profiles of epithelial–mesenchymal transition (EMT)-related (VIM, CDH1, CDH2, SNAI1, ZEB1, ZEB2, and TWIST1) and immune-regulatory (CD274 and PDCD1LG2) genes were compared. Moreover, the association between marker expression and clinical factors was analyzed. Among the 60 patients with CTCs, 48 (80.0%), 20 (33.3%), and 31 (51.7%) were positive for EPCAM, EGFR, and MET, respectively. A significant correlation was observed between CTCs expressing EPCAM and EGFR. CTCs expressing distinct markers showed differing EMT-related and immune-regulatory gene expression. EPCAM+ CTCs were associated with advanced-stage disease, while EGFR+ CTCs were correlated with locoregional relapse and shorter progression-free survival (p = 0.007; hazard ratio = 3.254). Patients with EPCAM/EGFR double-positive CTCs had the poorest prognosis. These findings emphasize the importance of marker selection in liquid biopsy technologies and highlight the need for improved detection methods and the further investigation of CTC biology. Full article

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous group of malignancies with poor survival outcomes, particularly in advanced stages. Identifying prognostic biomarkers could help improve patient management. miR-375, a small non-coding RNA, has been shown to influence tumor growth and immune responses, making it a candidate biomarker. This study aims to evaluate the role of miR-375 expression in predicting survival outcomes in HNSCC patients. A systematic review and meta-analysis were conducted according to PRISMA guidelines, incorporating data from six studies and the TGCA cohort, encompassing 452 patients. Fixed-effects models were applied to calculate aggregated hazard ratios (HRs) for overall survival (OS). Kaplan–Meier curves were analyzed using the Tierney method, and Trial Sequential Analysis (TSA) was performed to assess statistical power. Low miR-375 expression was associated with poorer OS, with an aggregated HR of 1.23 (95% CI: 1.10–1.37). Subgroup analysis showed consistent trends across oral and laryngeal squamous cell carcinoma. Sensitivity analysis confirmed these findings. TSA revealed that although the number of patients was sufficient, statistical power was insufficient to confirm a predefined risk reduction ratio (RRR) of 49%. Data from the TGCA cohort supported the meta-analysis findings, with an HR for OS of 1.32 (95% CI: 0.96–1.8). Low miR-375 expression is associated with worse survival outcomes in HNSCC patients, indicating its potential as a prognostic biomarker and therapeutic target. However, the retrospective nature of the included studies underscores the need for prospective research to validate these findings. Full article

Background: According to the 8th edition of the American Joint Committee on Cancer (AJCC), involvement of the masticator space and infratemporal fossa (ITF) in oral cancers indicates advanced disease (T4b), which is often considered unresectable. Previous studies have shown that the extent of ITF involvement influences management and outcomes. Therefore, to optimize management, T4b disease should be subclassified based on ITF involvement. Notably, infranotch disease has a more favorable prognosis compared to supranotch disease. Our study also observed that certain subsets of high anterior retroantral ITF involvement may be operable with favorable clinical outcomes. This study aims to derive a new image-based compartmentalization of high ITF involvement and assess its impact on the management and outcomes of oral head and neck squamous cell carcinoma (HNSCC) patients with high ITF involvement. Materials and Methods: This retrospective observational study included 154 non-metastatic, upfront unresectable locally advanced HNSCC patients who were fit for induction neoadjuvant chemotherapy (NACT). ITF involvement was classified into distinct compartments, and detailed staging of the primary tumor (T) and regional nodes (Ns) was performed. Clinical data, including patient demographics, treatment received, and follow-up notes, were documented. Prognosis was assessed using survival metrics: event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). The ITF was categorized into the following compartments: compartment 1 (low ITF: medial pterygoid), compartment 2 (anterior high ITF: retroantral fat), compartment 3 (posterior high ITF), including 3a (paramandibular compartment: paramandibular fat/temporalis), 3b (muscle compartment: lateral pterygoid), and 3c (Perineural compartment: pterygopalatine fossa and pterygomaxillary fissure). Results: Of the 154 cases, 142 (92%) were classified as T4b, with 63 (40.9%) having high ITF involvement and 79 (55.6%) having low ITF involvement. Twelve cases had T4a disease, which was deemed unresectable due to extensive nodal involvement. Subcompartmentalization of the 63 high ITF cases revealed 26 (41.2%) with compartment 2 involvement, 17 (26.9%) with compartment 3a involvement, 11 (17.4%) with compartment 3b involvement, and 9 (14%) with compartment 3c involvement. Disease progression following NACT was significantly higher in compartment 3c, which showed a poor response (p = 0.007). Univariate analysis for PFS revealed similar outcomes for compartments 1 and 2 (p = 0.692), while compartment 3 demonstrated poorer outcomes (p = 0.033). Among thosehigh ITF involvement, compartment 3c had the worst PFS outcome (p = 0.03). Conclusions: Baseline imaging plays a critical role in guiding individualized treatment and predicting clinical outcomes. Low ITF involvement and disease limited to the high retroantral fat compartment exhibit similar clinical outcomes. Among the posterior high ITF compartments, involvement of the pterygopalatine fossa and pterygomaxillary fissure (compartment 3c) is associated with the worst prognosis and poor response to chemotherapy. Subcompartmentalization of ITF involvement provides valuable prognostic information to tailor treatment strategies. Full article

Objectives: Head and neck squamous cell carcinoma (HNSCC) is characterized by complex genetic alterations. This study aimed to identify WBP5 as a promising therapeutic target and evaluate the effect of WBP5 expression on prognosis and treatment response in HNSCC. Methods: Publicly available datasets were comprehensively analyzed to investigate WBP5 expression through comprehensive bioinformatics analysis and functional validation. Results: WBP5 was particularly overexpressed in HNSCC, as analyzed through the Gene Expression Profiling Interactive Analysis version 2 (GEPIA2) database and validated using multiple Gene Expression Omnibus (GEO) datasets. Analysis with UALCAN confirmed that WBP5 expression was significantly higher in advanced cancer stages and tumor grades than that of normal samples. A Kaplan–Meier analysis demonstrated that patients overexpressing WBP5 had a poor prognosis. Moreover, WBP5 expression correlated with the overexpression of the epidermal growth factor receptor in HNSCC. In vitro experiments revealed that WBP5 knockdown significantly reduced FaDu cell proliferation and viability. Furthermore, silencing WBP5 enhanced cisplatin sensitivity, indicating its potential role in chemoresistance. Conclusions: These results indicate that WBP5 could act as a prognostic marker and a viable therapeutic target in HNSCC. Modulating WBP5 expression may represent a novel strategy to enhance treatment efficacy. Future studies should elucidate the precise mechanisms of WBP5 action and develop targeted therapies. This integrated approach, combining a comprehensive analysis of publicly available datasets with in vitro experimental validation provides strong evidence for the clinical significance of WBP5 in HNSCC. Full article