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Keywords = laryngeal squamous cell carcinoma

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15 pages, 4111 KiB  
Article
Impact of Tumor Budding in Head and Neck Cancers on Neck Lymph Node Metastasis and Prognosis
by Oğuz Gül, Özlem Çelebi Erdivanlı, Mehmet Birinci, Suat Terzi, Metin Çeliker, Oğuzhan Okçu, Çiğdem Öztürk, Tuğba Yemiş, Fatma Beyazal Çeliker, Zerrin Özergin Coşkun and Engin Dursun
J. Clin. Med. 2025, 14(15), 5224; https://doi.org/10.3390/jcm14155224 - 23 Jul 2025
Viewed by 350
Abstract
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 [...] Read more.
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
(This article belongs to the Section Otolaryngology)
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17 pages, 1435 KiB  
Article
Evaluation of GDF15 Significance as a Biomarker in Laryngeal Squamous Cell Carcinoma
by Aleksandra Romanowicz, Oskar Komisarek, Anna Klimaszewska-Wiśniewska, Paulina Antosik, Kacper Naglik, Joanna Czech, Witold Wrzesiński, Marta Kodzik, Magdalena Bodnar, Dariusz Grzanka and Paweł Burduk
J. Clin. Med. 2025, 14(14), 4870; https://doi.org/10.3390/jcm14144870 - 9 Jul 2025
Viewed by 388
Abstract
Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy with unsatisfactory survival rates, highlighting the need for reliable biomarkers to improve its diagnosis and prognosis. Growth differentiation factor 15 (GDF15), a protein implicated in various cancers, has not been thoroughly investigated [...] Read more.
Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy with unsatisfactory survival rates, highlighting the need for reliable biomarkers to improve its diagnosis and prognosis. Growth differentiation factor 15 (GDF15), a protein implicated in various cancers, has not been thoroughly investigated in LSCC. This study aimed to evaluate the significance of GDF15 expression in LSCC by integrating immunohistochemical analysis of archival tissue samples with RNA sequencing data from public databases (TCGA and GEO) to provide comprehensive clinical insights. Methods: We analyzed archival tissue samples from 65 patients with LSCC using immunohistochemistry and evaluated GDF15 expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Statistical analyses included Kaplan–Meier survival analysis and Cox proportional hazards regression to assess the correlation between GDF15 expression, clinicopathological variables, and survival outcomes. Results: GDF15 expression did not significantly differ between tumor and adjacent normal tissues. However, in the tissue macroarray (TMA) cohort, high GDF15 expression was significantly associated with a lower TNM stage and less advanced pT status. Kaplan–Meier analysis revealed that high GDF15 expression correlated with reduced overall survival in the TMA cohort, suggesting its utility in risk stratification. Multivariate analysis identified GDF15 as an independent prognostic factor for disease-free survival in LSCC. Conclusions: Our findings suggest that GDF15 may serve as a prognostic biomarker for LSCC, particularly in early-stage disease. Elevated GDF15 levels, which are associated with poorer overall survival, could be integrated into diagnostic panels to enhance risk stratification and inform treatment decisions. Furthermore, GDF15 may be a promising target for therapeutic intervention. Further research is warranted to validate these results and explore their potential in clinical practice. Full article
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11 pages, 1309 KiB  
Article
The Association Between Clinical Outcome and Expression of DNMT1, 3A, and 3B in Locally Advanced Laryngeal Carcinomas Treated by Definitive Radiotherapy
by Karlijn van den Bovenkamp, Gyorgy B. Halmos, Lorian Slagter-Menkema, Boukje A. C. van Dijk, Shibo Yu, Johannes A. Langendijk, Bernard F. A. M. van der Laan, Ed Schuuring and Bert van der Vegt
Cancers 2025, 17(11), 1741; https://doi.org/10.3390/cancers17111741 - 22 May 2025
Viewed by 455
Abstract
Objectives: This study aimed to evaluate the prognostic significance of DNA methyltransferases (DNMTs) expression, including DNMT1, DNMT3A, and DNMT3B, in assessing the risk of locoregional recurrence after radiotherapy in patients with locally advanced laryngeal squamous cell carcinoma (LSCC), in order to optimize [...] Read more.
Objectives: This study aimed to evaluate the prognostic significance of DNA methyltransferases (DNMTs) expression, including DNMT1, DNMT3A, and DNMT3B, in assessing the risk of locoregional recurrence after radiotherapy in patients with locally advanced laryngeal squamous cell carcinoma (LSCC), in order to optimize treatment decision making. Methods: A retrospective analysis was performed on pre-treatment biopsy tissues and clinical data from 58 patients with locally advanced LSCC (stages T3–T4, M0) treated with primary curative radiotherapy. DNMT expression was assessed through immunohistochemistry, and Cox regression analysis was applied to examine associations between methylation marker expression, demographic and clinical data, and both locoregional recurrence and disease-specific mortality. Results: Low expression of DNMT3A (p = 0.045) and the presence of locoregional lymph node metastases at diagnosis (N+-status) (p = 0.002) were associated with disease-specific mortality. Clinical N-status was also associated with locoregional recurrent disease after primary radiotherapy (p < 0.001). Expression of DNMT1 and DNMT3B, age, sex, and clinical T-status were not associated with locoregional recurrences or disease-specific mortality. Conclusions: Low expression of DNMT3A and the presence of regional lymph node metastases were independently associated with disease-specific mortality in patients with locally advanced LSCC treated primarily with definitive, curatively intended radiotherapy. Full article
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13 pages, 4513 KiB  
Article
Time-Intensity Curve Analysis of Contrast-Enhanced Ultrasound for Non-Ossified Thyroid Cartilage Invasion in Laryngeal Squamous Cell Carcinoma
by Milda Pucėtaitė, Dalia Mitraitė, Rytis Tarasevičius, Davide Farina, Silvija Ryškienė, Saulius Lukoševičius, Evaldas Padervinskis, Valdas Šarauskas and Saulius Vaitkus
Tomography 2025, 11(5), 57; https://doi.org/10.3390/tomography11050057 - 16 May 2025
Viewed by 527
Abstract
Objective: This study aimed to assess the diagnostic value of contrast-enhanced ultrasound (CEUS) time–intensity curve (TIC) parameters in detecting non-ossified thyroid cartilage invasion in patients with laryngeal squamous cell carcinoma (SCC). Methods: A CEUS TIC analysis was performed on 32 cases from [...] Read more.
Objective: This study aimed to assess the diagnostic value of contrast-enhanced ultrasound (CEUS) time–intensity curve (TIC) parameters in detecting non-ossified thyroid cartilage invasion in patients with laryngeal squamous cell carcinoma (SCC). Methods: A CEUS TIC analysis was performed on 32 cases from 27 patients with histologically confirmed laryngeal SCC. The diagnostic performance of time to peak (TTP), peak intensity (PI), wash-in slope (WIS), area under the curve (AUC), and their quantitative differences (∆TTP, ∆PI, ∆WIS, and ∆AUC) to discriminate between the invaded and the non-invaded non-ossified thyroid cartilage was determined using ROC analysis. A logistic regression analysis was employed to identify significant predictors. Results: In an ROC analysis, of all TIC parameters analyzed separately, ∆TTP showed the greatest diagnostic performance (AUC: 0.85). A ∆TTP cut-off of ≤ 8.9 s differentiated between the invaded and the non-invaded non-ossified thyroid cartilage with a sensitivity of 100%, specificity of 76.9%, and accuracy of 81.3%. A combination of ∆TTP and PI increased the AUC to 0.93, specificity to 100%, and accuracy to 96.8%, but reduced the sensitivity to 83.3%. Meanwhile, the visual assessment of enhancement on CEUS to detect cartilage invasion had 83.3% sensitivity and 84.6% specificity. In a univariate logistic regression, only ∆TTP was a significant predictor of non-ossified thyroid cartilage invasion (OR: 0.80; 95% CI: 0.64–1.00). For every second increase in ∆TTP, the probability of thyroid cartilage invasion decreased by 20%. Conclusions: CEUS TIC parameters, particularly a combination of ∆TTP and PI, showed high diagnostic performance in the detection of non-ossified thyroid cartilage invasion in laryngeal SCC. Full article
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32 pages, 1133 KiB  
Review
Laryngeal Cancer in the Modern Era: Evolving Trends in Diagnosis, Treatment, and Survival Outcomes
by Alexandru-Romulus Hut, Eugen Radu Boia, Diana Para, Gheorghe Iovanescu, Delia Horhat, Loredan Mikša, Maria Chiriac, Raphaël Galant, Alexandru Catalin Motofelea and Nicolae Constantin Balica
J. Clin. Med. 2025, 14(10), 3367; https://doi.org/10.3390/jcm14103367 - 12 May 2025
Viewed by 2875
Abstract
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and [...] Read more.
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes. Full article
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16 pages, 3010 KiB  
Article
Laryngeal Squamous Cell Carcinoma Is Characterized by a Stronger Expression of Nectin-4 Compared to Nectin-2
by Matej Maršić, Nives Jonjić, Maja Gligora Marković, Svjetlana Janković, Marko Velepič, Ilinko Vrebac, Lara Batičić and Tamara Braut
Curr. Issues Mol. Biol. 2025, 47(5), 296; https://doi.org/10.3390/cimb47050296 - 23 Apr 2025
Viewed by 582
Abstract
Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on [...] Read more.
Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on tissue microarray (TMA) samples derived from 31 patients who underwent total laryngectomy. The findings revealed heterogenous expression of both Nectin-2 and Nectin-4 in tumor cells and surrounding stroma, with Nectin-4 expression being significantly higher than Nectin-2 expression. Specifically, 74% of cases showed weak cytoplasmic staining for Nectin-2, while 41.93% exhibited strong cytoplasmic staining for Nectin-4. Both Nectin-2 and Nectin-4 expressions were more pronounced at the invasive tumor margins. Although no significant differences in Nectin-4 expression were observed across tumor grades (W = 83.500; z = −0.463; p = 0.658), differences in expression patterns were noted. Well-differentiated tumors (Grade 1), 80.65% of cases, showed predominantly membranous Nectin-4 staining, including in squamous epithelial cells of the mucosal surface. Conversely, in less-differentiated tumors (Grade 2 and 3), a shift toward cytoplasmic staining was evident. Specifically, 74.19% of Grade 2 tumors and 100% of Grade 3 tumors showed a predominant cytoplasmic localization of Nectin-4. This transition from membranous to cytoplasmic localization was also evident in the progression from normal superficial epithelium to malignant tissue. These observations suggest that alterations in the expression and subcellular localization of Nectin-4 may be associated with carcinogenesis and could serve as potential markers for the assessment of precancerous lesions and the aggressiveness of laryngeal tumors. Full article
(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)
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15 pages, 11937 KiB  
Article
Long-Term Quality of Life and Functional Outcomes in Patients with Total Laryngectomy
by Maria Octavia Murariu, Eugen Radu Boia, Adrian Mihail Sitaru, Cristian Ion Mot, Mihaela Cristina Negru, Alexandru Cristian Brici, Delia Elena Zahoi and Nicolae Constantin Balica
Cancers 2025, 17(6), 1011; https://doi.org/10.3390/cancers17061011 - 17 Mar 2025
Cited by 2 | Viewed by 1091
Abstract
Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these [...] Read more.
Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these treatments. Methods: This prospective observational cohort study was conducted at the ENT Clinic, Victor Babeș University of Medicine and Pharmacy, Timișoara; recruitment was conducted between October 2019 and January 2024. Seventy-five patients diagnosed with laryngeal squamous cell carcinoma (LSCC) were initially enrolled but only 15 patients (20%) completed the 12-month follow-up, with an attrition rate of 80%. Tumor stages ranged from T1 to T4a, with TL patients having a higher proportion of advanced-stage disease (Stage III–IV: 76%) compared to PL (45%) and CRT (50%). Validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Voice Handicap Index-30 (VHI-30), the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Outcome and Severity Scale (DOSS), were used to assess QoL, voice function, swallowing function, and psychological impact. Results: At 12 months, the global QoL score from the EORTC QLQ-H&N35 was lowest in TL patients (49.8 ± 10.9), significantly lower than both PL (61.2 ± 9.6, p = 0.002) and CRT (64.1 ± 7.8, p < 0.001). Post hoc Bonferroni analysis confirmed significant pairwise differences between TL vs. PL (p = 0.002) and TL vs. CRT (p < 0.001), while the difference between PL and CRT was non-significant (p = 0.14). TL patients had higher speech-related disability (VHI: 88.3 ± 12.6) and dysphagia prevalence (DOSS: 4.0 ± 1.2), with 16% remaining enteral feeding-dependent. Anxiety (HADS-A: 7.5 ± 2.9) and depression (HADS-D: 9.0 ± 3.2) were highest in TL patients, with 36% meeting clinical depression criteria at 12 months. Multivariable regression identified TL (OR = 3.92, 95% CI: 2.14–5.79, p < 0.001) and advanced tumor stage (OR = 2.85, 95% CI: 1.79–4.21, p = 0.002) as strong predictors of poor QoL. Kaplan–Meier analysis showed no significant OS differences (p = 0.12), but CRT patients had lower DFS (78%) compared to TL (82%) and PL (85%) (p = 0.048). Conclusions: TL patients experience the most significant impairments in QoL, speech, and social reintegration despite rehabilitation. CRT patients show higher recurrence rates but better QoL, while PL offers the best balance of function and survival. These findings highlight the need for long-term survivorship support tailored to treatment type. Full article
(This article belongs to the Special Issue Cancer Survivorship: During and After Treatment)
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17 pages, 2243 KiB  
Article
Oxidative Stress Biomarkers in Laryngeal Squamous Cell Carcinoma and Their Clinical Implications: Preliminary Results
by Barbara Verro, Carmelo Saraniti, Diana Di Liberto, Giovanni Pratelli, Marianna Lauricella and Daniela Carlisi
Biomedicines 2025, 13(3), 667; https://doi.org/10.3390/biomedicines13030667 - 8 Mar 2025
Viewed by 885
Abstract
Background/Objectives: Laryngeal squamous cell carcinoma represents one of the most common head and neck cancers with a five-year survival rate that, despite diagnostic and therapeutic advances, has not shown any significant improvement in recent decades. Oxidative stress, generated by an imbalance between [...] Read more.
Background/Objectives: Laryngeal squamous cell carcinoma represents one of the most common head and neck cancers with a five-year survival rate that, despite diagnostic and therapeutic advances, has not shown any significant improvement in recent decades. Oxidative stress, generated by an imbalance between reactive oxygen species and cellular antioxidant systems, is considered a central mechanism in the carcinogenesis of laryngeal squamous cell carcinoma, causing DNA damage and genomic alterations. Methods: This prospective observational paired case–control study focused on the evaluation of antioxidant proteins, such as superoxide dismutase, catalase, heme-oxygenase 1, vimentin, metallothionein, and nuclear factor erythroid 2-related factor 2, in cancer tissues from fifteen patients with laryngeal squamous cell carcinoma, using adjacent healthy tissues as controls. Results: The results show a statistically significant overexpression of all proteins analyzed in cancer tissues compared to controls, with relevant correlations between specific biomarkers and clinical characteristics, age, sex, smoking habits, and degree of tumor differentiation. Conclusions: These preliminary studies, while limited by sample size and the complexity of molecular regulation, indicate that the overexpression of antioxidant enzymes in laryngeal squamous cell carcinoma tissues, along with their correlations with key clinical parameters, underscores a context-dependent role of oxidative stress in tumor progression. A deeper understanding of oxidative stress mechanisms could contribute to advance personalized management strategies for laryngeal squamous cell carcinoma, potentially improving treatment outcomes and patient prognosis. Full article
(This article belongs to the Special Issue Novel Approaches towards Targeted Head and Neck Cancer Therapies)
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13 pages, 809 KiB  
Article
The Impact of Paratracheal Lymphadenectomy on Survival After Esophagectomy: A Nationwide Propensity Score Matched Analysis
by Eliza R. C. Hagens, B. Feike Kingma, Mark I. van Berge Henegouwen, Alicia S. Borggreve, Jelle P. Ruurda, Richard van Hillegersberg and Suzanne S. Gisbertz
Cancers 2025, 17(5), 888; https://doi.org/10.3390/cancers17050888 - 5 Mar 2025
Viewed by 712
Abstract
Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic [...] Read more.
Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic esophagectomy with two-field lymphadenectomy were included from the Dutch Upper Gastro-intestinal Cancer Audit registry. After 1:1 propensity score matching of patients with and without paratracheal lymphadenectomy within histologic subgroups, short-term outcomes and overall survival were compared between the two groups. Results: A total of 1154 patients with adenocarcinoma and 294 patients with squamous cell carcinoma were matched. Lymph node yield was significantly higher (22 versus 19 nodes, p < 0.001) in patients with paratracheal lymphadenectomy for both tumor types. Paratracheal lymphadenectomy was associated with more recurrent laryngeal nerve injury (10% versus 5%, p = 0.002) and chylothorax in patients with adenocarcinoma (10% versus 5%, p = 0.010) and with more anastomotic leakage in patients with squamous cell carcinoma (42% versus 27%, p = 0.014). The 3- and 5-year survival in patients with and without a paratracheal lymphadenectomy were for adenocarcinoma, respectively, 58% versus 56% and 48% in both groups (log rank: p = 0.578) and for patients with a squamous cell carcinoma, 62% in both groups and 57% versus 54% (log rank: p = 0.668). Conclusions: The addition of paratracheal lymphadenectomy significantly increases lymph node yield in transthoracic esophagectomy but did not result in improved survival for esophageal cancer patients in the current dataset. However, there was an increase in postoperative morbidity in patients who underwent a paratracheal lymphadenectomy. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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20 pages, 2124 KiB  
Review
The Prognostic Role of miR-375 in Head and Neck Squamous Cell Carcinoma: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis
by Mario Dioguardi, Gennaro Musella, Maria Eleonora Bizzoca, Diego Sovereto, Ciro Guerra, Pietro Laterza, Angelo Martella, Lorenzo Lo Muzio, Marina Di Domenico, Stefania Cantore and Andrea Ballini
Int. J. Mol. Sci. 2025, 26(5), 2183; https://doi.org/10.3390/ijms26052183 - 28 Feb 2025
Viewed by 904
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular Pharmacology)
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11 pages, 423 KiB  
Case Report
Metastasis of Squamous Cell Carcinoma of the Larynx to the Right Adrenal Gland—A Case Report
by Eliza Działach, Michał Simlot, Karolina Osowiecka, Elżbieta Nowara, Jarosław Markowski and Mateusz Grajek
Clin. Pract. 2025, 15(3), 49; https://doi.org/10.3390/clinpract15030049 - 26 Feb 2025
Viewed by 795
Abstract
Background/Objectives: Malignant adrenal tumors comprise both primary adrenal neoplasms and metastatic lesions, with the latter being significantly more common. Squamous cell carcinoma (SCC) of the larynx is a prevalent head and neck cancer that typically spreads to the cervical lymph nodes, with [...] Read more.
Background/Objectives: Malignant adrenal tumors comprise both primary adrenal neoplasms and metastatic lesions, with the latter being significantly more common. Squamous cell carcinoma (SCC) of the larynx is a prevalent head and neck cancer that typically spreads to the cervical lymph nodes, with distant metastases being rare. Among such metastases, adrenal gland involvement is particularly uncommon, presenting unique diagnostic and therapeutic challenges. The study aimed to explore the progression, diagnostic process, and therapeutic management of a rare case of SCC of the larynx metastasizing to the adrenal gland, highlighting the role of advanced diagnostic imaging and a multidisciplinary approach in patient care. Methodology: A 66-year-old male with grade 3 SCC of the larynx underwent total laryngectomy, selective cervical lymphadenectomy, and radiotherapy with a dose of 70 Gy. Chemotherapy was discontinued due to hematological complications. Post-treatment monitoring included CT and PET-CT imaging, leading to the detection of a large adrenal mass. Surgical biopsy confirmed metastatic SCC in the adrenal gland, as resection was not feasible due to extensive invasion. Diagnostic imaging and histopathological examination were complemented by biochemical evaluations to assess hormonal activity. Results: The adrenal mass was identified as a metastasis from the laryngeal SCC. Imaging studies provided detailed insights into the lesion’s size, metabolic activity, and non-functional status. Despite comprehensive efforts, the tumor was deemed unresectable, highlighting the aggressive nature of the disease and the limitations of current therapeutic modalities. Conclusions: This rare case emphasizes the importance of early detection, advanced imaging techniques, and interdisciplinary collaboration in managing complex metastatic presentations. It underscores the critical need for further research into systemic treatments, such as immunotherapy, and the development of standardized protocols for rare metastatic patterns. The study contributes to the growing body of literature on the management of uncommon cancer metastases, advocating for individualized patient care and innovation in treatment strategies. Full article
(This article belongs to the Special Issue Clinical Outcome Research in the Head and Neck)
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13 pages, 578 KiB  
Systematic Review
A Systematic Review of Circulating miRNAs Validated by Multiple Independent Studies in Laryngeal Cancer
by Andreea Banta, Felix Bratosin, Ioana Golu, Ana-Olivia Toma and Eugenia Maria Domuta
Diagnostics 2025, 15(3), 394; https://doi.org/10.3390/diagnostics15030394 - 6 Feb 2025
Cited by 3 | Viewed by 1230
Abstract
Background and Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with significant morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis and prognosis. This systematic review aims to identify circulating miRNAs associated [...] Read more.
Background and Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with significant morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis and prognosis. This systematic review aims to identify circulating miRNAs associated with LSCC, emphasizing those validated by at least two independent studies to improve reliability and clinical applicability. Methods: An extensive literature search was performed in the PubMed, Scopus, and Web of Science databases up to October 2024, using keywords related to LSCC and circulating miRNAs. Studies involving human participants that provided quantitative data on circulating miRNA expression levels and their clinical correlations were included. Data extraction and quality assessment were conducted following standardized protocols, highlighting miRNAs reported in multiple studies. Results: Nine high-quality studies encompassing 660 patients with LSCC and 212 controls were included. Several miRNAs were consistently identified across these studies. miR-21-5p was upregulated in four studies and associated with advanced disease stages, lymph node metastasis, and decreased survival rates. miR-125b-5p and miR-126-3p were consistently downregulated, linked to advanced clinical stages and poor tumor differentiation. miR-27a-3p was upregulated in two studies and correlated with poor prognosis, promoting LSCC progression by targeting Smad4. Additionally, miR-33a-5p was identified as a potential diagnostic biomarker with high sensitivity and specificity. These miRNAs show potential as non-invasive biomarkers for the diagnosis and prognosis of LSCC. Conclusions: This systematic review highlights specific circulating miRNAs—particularly miR-21-5p, miR-125b-5p, miR-126-3p, miR-27a-3p, and miR-33a-5p—as promising biomarkers for LSCC. The consistent findings across independent studies emphasize their potential clinical utility in early detection, prognostic assessment, and therapeutic targeting. However, further validation in larger and more diverse populations, along with the standardization of detection methods, is necessary before these biomarkers can be implemented in clinical practice. Full article
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13 pages, 1898 KiB  
Systematic Review
Sentinel Node Biopsy in Laryngeal Cancer: A Systematic Review and Meta-Analysis
by Pegah Sahafi, Ramin Sadeghi, Emran Askari, Azadeh Sahebkari, Mitra Ghahraman, Ehsan Khadivi, Kamran Khazaeni, Vahid Reza Dabbagh Kakhki and Sara Harsini
Diagnostics 2025, 15(3), 366; https://doi.org/10.3390/diagnostics15030366 - 4 Feb 2025
Viewed by 1112
Abstract
Background: Sentinel lymph node (SLN) biopsy offers a minimally invasive approach to staging lymph node involvement in laryngeal squamous cell carcinoma (SCC). Despite its adoption in other cancers, its accuracy in laryngeal SCC remains under investigation. This systematic review and meta-analysis evaluates the [...] Read more.
Background: Sentinel lymph node (SLN) biopsy offers a minimally invasive approach to staging lymph node involvement in laryngeal squamous cell carcinoma (SCC). Despite its adoption in other cancers, its accuracy in laryngeal SCC remains under investigation. This systematic review and meta-analysis evaluates the diagnostic performance of SLN mapping in laryngeal cancer. Methods: A systematic search of MEDLINE, Scopus, and Google Scholar was conducted using the keywords “(larynx OR laryngeal) AND sentinel”, with no date or language restrictions. Studies reporting SLN detection rates and/or sensitivity in laryngeal SCC were included. A random-effects model was applied for data pooling, and subgroup analyses were performed based on tumor location (supraglottic versus transglottic) and mapping material (radiotracer versus blue dye). Publication bias was assessed using funnel plots and statistical methods. Results: Nineteen studies, encompassing 366 patients, were analyzed. The overall pooled SLN detection rate was 90.8% (95% CI: 86–94.1), and sensitivity was 88% (95% CI: 81–94). Supraglottic tumors demonstrated superior outcomes (detection rate: 93.7%, sensitivity: 96%) compared to transglottic tumors (detection rate: 84.7%, sensitivity: 71%). Radiotracers significantly outperformed blue dye, with detection rates of 90.8% versus 81.5% and sensitivities of 88% versus 77%. Conclusions: SLN mapping is a reliable technique for staging laryngeal SCC, particularly for supraglottic tumors, where high detection rates and sensitivity were observed. Radiotracers offer superior performance compared to blue dye, underscoring their clinical value. These findings support the feasibility and accuracy of SLN biopsy in laryngeal cancer, while emphasizing the importance of tumor location and mapping material. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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13 pages, 639 KiB  
Systematic Review
Clinical and Pathological Staging Discrepancies in Laryngeal Cancer: A Systematic Review
by Giancarlo Pecorari, Andrea Lorenzi, Matteo Caria, Gian Marco Motatto and Giuseppe Riva
Cancers 2025, 17(3), 455; https://doi.org/10.3390/cancers17030455 - 28 Jan 2025
Cited by 2 | Viewed by 1469
Abstract
Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent and challenging malignancies of the head and neck. Clinical staging (cTNM) plays a pivotal role in therapeutic decision-making. However, current imaging modalities often fall short, resulting in discrepancies between cTNM [...] Read more.
Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent and challenging malignancies of the head and neck. Clinical staging (cTNM) plays a pivotal role in therapeutic decision-making. However, current imaging modalities often fall short, resulting in discrepancies between cTNM and pathological staging (pTNM). This systematic review aimed to critically evaluate the existing literature on the concordance between clinical and pathological staging of LSCC, quantifying staging inaccuracies and highlighting the prevalence of both under- and overstaging at diagnosis. Methods: A comprehensive search of the English-language literature was conducted across multiple databases, including PubMed, Embase, Scopus, the Cochrane Library, and Web of Science. Eligibility was limited to retrospective case series and observational studies reporting sufficient data to directly correlate individual patients’ cTNM and pTNM classifications. Results: Thirty-one studies comprising 7939 patients met the inclusion criteria. The overall concordance rate between cT and pT was approximately 86.43%. The concordance rates between cT and pT were 82.41%, 82.03%, 78.14%, and 89.64% for cT1, cT2, cT3, and cT4, respectively. Most discordant cases in cT2 and cT3 involved understaging at clinical diagnosis. Conclusions: The limited accuracy of clinical staging in reflecting the true extent of disease remains a critical challenge in the management of LSCC. The inability of current imaging techniques to reliably detect the subtle invasion of key anatomical structures contributes to both under- and overstaging, with significant clinical implications. For patients undergoing non-surgical organ-preservation strategies, these inaccuracies may adversely affect oncologic outcomes. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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14 pages, 1206 KiB  
Article
Shorter Time to Biopsy of Patients with Head and Neck Squamous Cell Carcinoma During the COVID-19 Pandemic in Hungary
by Éva Szabó, Eszter Kopjár, László Rumi, Szabolcs Bellyei, Antal Zemplényi, Emese Mátyus, Eszter Édes, János Girán, István Kiss, István Szanyi and Éva Pozsgai
Cancers 2025, 17(3), 360; https://doi.org/10.3390/cancers17030360 - 23 Jan 2025
Viewed by 936
Abstract
Background/objectives: The goal of this investigation was to compare the time to biopsy (TBI) and time to treatment (TTI) for head and neck squamous cell carcinoma (HNSCC) patients before and during the COVID-19 pandemic and to examine the effect of demographic and clinical [...] Read more.
Background/objectives: The goal of this investigation was to compare the time to biopsy (TBI) and time to treatment (TTI) for head and neck squamous cell carcinoma (HNSCC) patients before and during the COVID-19 pandemic and to examine the effect of demographic and clinical characteristics on these intervals. Methods: Our retrospective study at a large regional Hungarian cancer center analyzed data from patients aged 18 or older diagnosed with HNSCC between 1 January 2017 and 15 March 2020 (pre-COVID-19 period) and 16 March 2020 to 13 May 2021 (COVID-19 period). We calculated the time from initial physician contact to biopsy (TBI) and from biopsy to treatment initiation (TTI) and performed descriptive and exploratory statistical analyses. Results: The median TBI decreased significantly (6 vs. 3 days; p = 0.008), while the median TTI was not affected significantly (28 vs. 29 days; p = 0.972) pre-pandemic and during the pandemic, respectively. Residence in a village was linked to a significant reduction in median TBI during the pandemic (p = 0.000), coinciding with a higher proportion of rural patients diagnosed with oral cavity/oropharyngeal cancers during the pandemic (50.3% pre-pandemic vs. 67.4% during pandemic, p = 0.044). Median TTI decreased significantly during the pandemic for patients with laryngeal tumors (27.5 vs. 18.5 days; p = 0.012). Conclusions: Our study, one of a few from this region, provides insights into HNSCC patient waiting times. Improvement in TBI likely resulted from the availability of telemedicine, reduced diagnostic demands from non-cancer patients, and an increased incidence of oral cavity/oropharyngeal cancer among rural patients. Full article
(This article belongs to the Special Issue How COVID-19 Affects Cancer Patients)
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