Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

FNA diagnosis of secondary malignancies in the parotid gland: over 20 years of experience from a single institute.

INTRODUCTION: Metastatic solid tumors account for a significant portion of malignancies in the parotid gland. Fine-needle aspiration (FNA) is a primary tool to diagnose these tumors. MATERIALS AND METHODS: We retrospectively reviewed 134 FNA cases of metastatic solid tumors affecting the parotid gland, spanning from 2000 to 2023 at our institute. We summarized the medical histories, cytology diagnoses, correlations with surgical resections, clinical treatments, and follow-up outcomes. RESULTS: The patient cohort included 107 male and 27 female patients, with a median age of 71 years (range: 4-96 years). Eighty-five percent of metastases (113 of 134) originated from head and neck (H&N) malignancies, comprising 66% from cutaneous source and 19% from mucosal sites. The most frequent primary sites outside the H&N were lung (4%), kidney (2%), and non-H&N skin (2%). Sixty-eight percent of metastases (92 of 134) were squamous cell carcinoma (SqCC) including 61% conventional type and 7% human papillomavirus-related SqCC. Melanoma is the second most common metastatic malignancy (28 of 134, 21%). The median time from primary diagnosis to metastasis was 10 months (range: 0 to 132 months). During clinical follow-up, 59 (44%) patients died from the disease in a median follow-up of 10 months (range: 2 to 56 months). CONCLUSIONS: This study represents one of the largest series of secondary malignancies in the parotid gland collected from a single institution. Most of these tumors are metastases from H&N malignancies, with cutaneous SqCC being the most prevalent primary site and histology. Accurate diagnosis relies heavily on clinical history, morphologic evaluation, and ancillary studies.

Pigmented basal cell carcinoma mimicking nodular melanoma.

The most common form of primary skin cancer is basal cell carcinoma (BCC). Pigmented BCC is a less common clinical presentation in BCC spectrum, where the tumour contains pigment. Some cases can exhibit morphological features that mimic those of nodular melanoma (NM). We present a woman in her late 40's who had an asymptomatic firm, hyperpigmented nodule on the right cheek resembling pigmented NM. Dermoscopy showed diffuse hyperpigmentation with irregular shiny surface and a solitary haemorrhagic crust. Melanoacanthoma and irritated seborrheic keratosis were the other differentials considered. Punch biopsy showed features of trichoepithelioma initially, subsequent complete excision was suggestive of pigmented BCC.Mortality related to BCC is rare, whereas NM is aggressive. Hence, clinicians need to be aware of this rare presentation of BCC as a hyperpigmented nodule, particularly in dark-skinned individuals. Timely differentiation between melanoma and BCC is crucial given their differing prognosis.

Prevention of radiation induced dermatitis in head and neck cancer patients using cryptomphalus aspersa secretion.

INTRODUCTION: Radiotherapy (RT) is a technique widely used in oncology, acquiring special prominence in head and neck cancer (HNC). RT of HNC may be associated with secondary effects including skin reaction, being dermatitis the most common radio-induced side effect during treatment. PURPOSE: The use of a wide variety of agents is reported to handle skin toxicity. The aim of the present work is to evaluate the different level-concentration of Snail Cryptomphalus Aspersa (SCA) that best protect from radiation-induced radiodermatitis in HNC. MATERIAL AND METHOD: We performed a single institutional pilot study to assess the skin toxicity with 0%, 5%, 10% and 15% SCA concentration during RT treatment and 1 and 3 months after the treatment finished according to the Radiation Therapy Oncology Group (RTOG) scoring. A total of 72 patients with HNC diagnosis who received RT with/without Chemotherapy (Ch) between January of 2018 and June of 2020 were assessed. Radiodermatitis grade was stastistically correlated with the SCA level-concentration and with the influence of extranodal extension status (ENE). RESULTS: A reduction in the rate of grade ≥ II patients' dermatitis was dependent on SCA level-concentration. We found that with higher SCA level-concentration (10 and 15%, patients had 34 and 38% grade ≥ II respectively), this was less than with 0 and 5% SCA level-concentration where a 58% radiodermatitis grade ≥ II was found by Cox regression analysis; p = 0.017 and p = 0.045 respectively. CONCLUSION: We could conclude that the application of a 10-15% SCA level-concentration after adjusting by ENE, was the best concentration to reduce the rate of grade ≥ II radiodermatitis.

Radiomics-based model for prediction of TGF-ß1 expression in head and neck squamous cell carcinoma.

OBJECTIVE: To explore the connection between TGF-ß1 expression and the survival of patients with head and neck squamous cell carcinoma (HNSCC), as well as whether non-invasive CT-based Radiomics can predict TGF-ß1 expression in HNSCC patients. METHODS: Data on transcriptional profiling and clinical information were acquired from the TCGA database and subsequently categorized based on the TGF-ß1 expression cutoff value. Based on the completeness of enhanced arterial phase CT scans, 139 HNSCC patients were selected. The PyRadiomics package was used to extract radiomic features, and the 3D Slicer software was used for image segmentation. Using the mRMR_RFE and Repeat LASSO algorithms, the optimal features for establishing the corresponding gradient enhancement prediction models were identified. RESULTS: A survival analysis was performed on 483 patients, who were divided into two groups based on the TGF-ß1 expression cut-off. The Kaplan-Meier curve indicated that TGF-ß1 was a significant independent risk factor that reduced patient survival. To construct gradient enhancement prediction models, we used the mRMR_RFE algorithm and the Repeat_LASSO algorithm to obtain two features (glrlm and ngtdm) and three radiation features (glrlm, first order_10percentile, and gldm). In both the training and validation cohorts, the two established models demonstrated strong predictive potential. Furthermore, there was no statistically significant difference in the calibration curve, DCA diagram, or AUC values between the mRMR_RFE_GBM model and the LASSO_GBM model, suggesting that both models fit well. CONCLUSION: Based on these findings, TGF-ß1 was shown to be significantly associated with a poor prognosis and to be a potential risk factor for HNSCC. Furthermore, by employing the mRMR_RFE_GBM and Repeat_LASSO_GBM models, we were able to effectively predict TGF-ß1 expression levels in HNSCC through non-invasive CT-based Radiomics.

A Veiled Lymphatic Malformation: Stridor in a Child.

Lymphatic malformation (LM) is a congenital lymphatic dysplasia associated with the p110α subunit of PI3K (PIK3CA) mutation. A two-year-old boy presented with a history of noisy breathing from the age of two months, which was progressively worsening. Inspiratory stridor was audible with subcostal recession. Flexible nasopharyngolaryngoscopy (FNPLS) revealed an enlarged right arytenoid. Other supraglottic structures were normal, and bilateral vocal cords were mobile. Direct laryngoscopy showed that the right arytenoid was enlarged with a smooth surface. On the subsequent visit, there was a painless soft lateral neck swelling, 4 cm x 4 cm in size, with normal skin. MRI confirmed LM with the predominantly macro-cystic component, involving primarily the right neck and upper mediastinum, causing airway compression. Sirolimus therapy was initiated, and at one month of follow-up after the treatment, his stridor had improved. The incidence of stridor secondary to head and neck tumors such as teratomas, hemangiomas, and LM accounts for less than 3%. The typical manifestation of LM often involves a painless, soft, and compressible mass that progressively increases in size. Features of macrocystic LM on MRI are multilocular and hyperintense cystic mass on T2-weighted imaging. The treatment methods for LM include surgical and non-surgical options. Despite being an off-label application, the response rate of sirolimus therapy in children with LM is reported to be 91%, and the first clinical response was observed in less than three weeks. Stridor is frequently encountered in children but rarely due to head and neck tumors. However, as in our case, a large LM may cause recurrent airway obstruction, and the neck swelling may appear later. Atypical airway findings, especially endoscopic examination, in a child with stridor should be complemented with imaging to examine the possibility of extra-laryngeal mass or external compression.

Targeting superficial cancers with gold nanoparticles: a review of current research.

Superficial cancers typically refer to cancers confined to the surface layers of tissue. Low-targeting therapies or side effects prompt exploration of novel therapeutic approaches. Gold nanoparticles (AuNPs), due to their unique optical properties, serve as effective photosensitizers, enabling tumor ablation through photothermal therapy (PTT). PTT induced by AuNPs can be achieved through light sources externally applied to the skin. Near-infrared radiation is the main light candidate due to its deep tissue penetration capability. This review explores recent advancements in AuNP-based PTT for superficial cancers, specifically breast, head and neck, thyroid, bladder and prostate cancers. Additionally, challenges and future directions in utilizing AuNPs for cancer treatment are discussed, emphasizing the importance of balancing efficacy with safety in clinical applications.

[Box: see text].

Cold atmospheric plasma activated media selectively affects human head and neck cancer cell lines.

OBJECTIVE: Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their in vitro selectivity against head and neck cancer cells (HNC). METHODS: PAM were obtained by exposing 2 and 5 mL of cell culture medium to CAP for 5, 10 and 20 min at a 6 mm working distance. Anions kinetics was evaluated by ion chromatography. Cell proliferation inhibition, apoptosis occurrence, and cell cycle modifications were assessed by MTS and flow cytometry, on human epidermal keratinocyte (HaCaT) and HNC cell lines HSC3, HSC4 and A253. RESULTS: The 2 mL conditions showed a significant reduction in cell proliferation whereas for the 5 mL the effect was milder, but the time-dependence was more evident. HaCaT were unaffected by the 5 mL PAM, indicating a selectivity for cancer cells. CONCLUSIONS: The media chemical composition modified by CAP exposure influenced cell proliferation by modulating cell cycle and inducing apoptosis in cancer cells, without affecting normal cells.

The Impact of Preoperative Flexible Fiberoptic Laryngoscopy on Anesthesia's Intubation Plans.

Purpose: To assess the value of conducting a preairway management review of flexible fiberoptic laryngoscopy examinations (FFL) by the anesthesia team for patients with head and neck cancer and to examine its impact on intubation strategies and overall patient safety. Methods: Prospective study at a single tertiary referral center including patients with stage T2 and greater cancers of the oropharynx, hypopharynx, or larynx who underwent intubation by the anesthesia team between May 2022 and April 2023. Pre- and postoperative surveys gathered data on the intubation plan, including details such as method, sedation, patient respiration, laryngoscope, tube size, and use of paralysis. Postoperative surveys gauged the FFL's subjective utility and documented intubation details and complications. Results: Thirty-four patients (49-87 years of age) were included in the study. Eleven intubation plans were changed after reviewing the FFL, while 23 were not. Although this was a pilot study, there was no significant correlation between location of the tumor and change in intubation plan. Of the 34 intubations, 9 were executed based on the plan after reviewing FFL. The majority of the attending anesthesiologists agreed or strongly agreed that seeing the FFL was more helpful than reading the findings in clinic notes and that reviewing the FFL was helpful in creating the intubation plan, 77% and 88%, respectively. Conclusion: Reviewing the FFL led to changes in the anesthesia team's intubation plan in 32% of the cases in our pilot study. While these findings are promising, they highlight the need for further research with larger sample sizes and across multiple centers to validate the impact of FFL on intubation strategies for patients with stage T2 and greater cancers of the oropharynx, hypopharynx, or larynx.

Awake Tracheostomy in a Pediatric Patient.

Awake tracheostomy is rare in the pediatric population. We describe the case of a 10-year-old male who underwent awake tracheostomy due to airway obstruction from an oropharyngeal rhabdomyosarcoma. Given the varying medical understanding and communication skills in children, advanced planning and interdisciplinary collaboration are essential to keep the patient calm and safe during awake tracheostomy.

Evidence summary on the rehabilitative management of dysphagia during radiotherapy for head and neck cancer patients.

Objective: To retrieve, extract, integrate and evaluate evidence on the rehabilitation of dysphagia in patients undergoing radiotherapy for head and neck cancer (HNC), and to provide a basis for the development of a rehabilitation management protocol for dysphagia in patients undergoing radiotherapy for HNC. Methods: An evidence-based systematic search of the literature related to the rehabilitation of dysphagia in patients with HNC during radiotherapy was conducted from January 2013 to March 2023, and the corresponding evaluation tools were selected according to the different types of literature for quality evaluation. "The Joanna Briggs Institute (JBI) evidence pre-grading system was used to evaluate the quality of the evidence. Results: A total of 17 articles were included, including 3 guidelines, 5 expert articles, 1 clinical decision, 1 practice recommendation, 2 evidence summaries and 5 systematic evaluations. A final total of 28 pieces of evidence were summarised, including 6 areas of swallowing disorder screening and assessment, physiotherapy, preventive swallowing function training, feeding management, pain control, and oral care. Conclusion: This study forms a multidisciplinary collaborative evidence summary for the rehabilitation management of dysphagia in patients undergoing radiotherapy for HNC, but the application of some of the evidence needs to be carried out in the context of the clinical setting and patient-specific circumstances for the rehabilitation evidence selected for patients' dysphagia to improve their swallowing function and their swallowing-related quality of life and reduce the occurrence of related complications.

Assessing the diagnostic utility of tRNA-derived fragments as biomarkers of head and neck cancer.

Roughly 54,000 individuals are diagnosed with head and neck cancers in the United States yearly. Transfer RNA-derived fragments (tRF) are the products of enzymatic cleavage of precursor tRNAs, and have been proposed for use as biomarkers of head and neck cancer. In this study, we aim to further analyze the utility that tRFs might provide as biomarkers of head and neck cancer. tRF read counts were obtained for 453 tumor and 44 adjacent normal tissue samples and used to construct a gradient boosting diagnostic model. Although we identified 129 tRFs that were significantly dysregulated between these samples, the model achieved a sensitivity of only 69 % and a specificity of 59 %. tRFs are thought to induce the degradation of mRNA transcripts containing a complementary "seed" region. Despite the above performances, we chose to explore this concept of translational regulation by analyzing these tRFs for inverse correlation to the expression of select oncogenes and tumor suppressor genes implicated in head and neck cancer. Among others, CysGCA 5'-half and LysCTT 3'-tRF were upregulated in the tumor samples, and corresponded to decreased expression of PIK3R1, AKT1, and CPEB3. These transcripts were further found to contain numerous significantly complementary sites at which tRF-mediated mRNA degradation might occur. Although these tRFs did appear to correlate to many of the oncogenic metrics analyzed, we believe that additional research is needed before they might be used to improve the diagnosis, treatment, and survival of patients with this disease.

Risk prediction of complicated course in patients undergoing major head and neck surgery with free flap reconstruction.

The British Association of Oral and Maxillofacial Surgeons (BAOMS) Quality and Outcomes in Oral and Maxillofacial Surgery (QOMS) reconstructive audit aims to provide surgical teams with risk adjusted comparative performance data. The goal is to enable surgeons to optimise surgical pathways. Risk adjustment requires that data on appropriate predictive variables are collected. This study looked at variables predicting major complications and flap failure in a single institution with the aim of determining whether the QOMS dataset adequately captures the appropriate data points. A prospective database of head and neck flap procedures and associated postoperative complications has been maintained in the maxillofacial surgery department since August 2009 up to August 2022 (n=1327). A total of 25 putative risk variables were extracted from the health records for each patient. The outcomes of interest were total flap failure and major complications. Independent predictors of flap failure were recipient site (sinonasal/anterior skull base), previous major surgery, previous major surgery and radiotherapy, and flap selection. For major complications ACE-27 comorbidity score, flap type, use of tracheostomy, elevated preoperative plasma C-reactive protein (CRP) and flap selection were independently predictive. Apart from preoperative activated innate immunity all relevant risk stratification variables identified in this study form part of the QOMS dataset. QOMS is therefore likely to adequately risk stratify patients based upon currently collected variables.

Chemotherapy/Radiotherapy-Induced Dysphagia in Head and Neck Tumors: A Challenge for Otolaryngologists in Low- to Middle-Income Countries.

Head and neck cancer accounts for 2.8% of all cancers and a large proportion of these patients have a locally advanced stage of the disease, for which chemotherapy and radiation therapy are potentially curative treatments. Dysphagia is one of the most common chemoradiotherapy-related side effects in head and neck cancer since it can lead to life-threatening complications. Reports from the current literature suggest better swallowing outcomes with intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3DCT). However, in low-/middle-income countries, multiple healthcare access barriers to 3DCT that may lead to higher rates of chemo/radiotherapy related adverse events. This narrative review provides a comprehensive appraisal of published peer-reviewed data, as well as a description of the clinical practice in an otolaryngology referral center in Colombia, a low-income country.

Incidental Finding of Double Posterior Belly of Digastric Muscle in Head and Neck Cancer Patient.

OBJECTIVES: The digastric muscles have important roles in swallowing, chewing, speech, and landmark identification during neck dissection. The posterior belly of the digastric muscle (PBDM) is often useful for defining boundaries in surgical neck dissection as it contributes to the carotid, submandibular, and submental triangles. The cadaveric prevalence rate of anatomic variations in the digastrics has been reported to be 31.4% of the population with most occurring in relation to the anterior belly of the digastric muscle (ABDM). Few reports describe variations in the PBDM. While anatomic variants of the digastric muscles do not present with clinical manifestations, they can be mistaken as neck masses and contribute to intraoperative complications. METHODS: We present a case report of a 73-year-old male with a past medical history significant for Parkinson's Disease, who was incidentally found to have a duplicate PBDM intraoperatively while receiving surgical management of a left buccal squamous cell cancer. RESULTS: Nine months prior to surgery, the patient began experiencing trismus and some mild dysphagia that were eventually worked up to reveal left buccal squamous cell carcinoma (SCC). Prior to this, the patient did not have clinical symptoms demonstrating dysfunction that could be related to or indicative of this anatomical abnormality preceding symptoms related to left buccal SCC growth. The procedure included a wide local excision, left modified radical neck dissection and left submental artery island flap with suprahyoid neck dissection. The superior duplicate PBDM was found to be overlying the stylohyoid muscle. CONCLUSIONS: It is important for surgeons operating in the head and neck to be aware of the possibility of this rare variation, and to be conscientious when it is identified so that it does not prohibit or limit a thorough dissection of the neck structures where oncologic clearance is paramount.

The Role of ctDNA and Liquid Biopsy in the Diagnosis and Monitoring of Head and Neck Cancer: Towards Precision Medicine.

Recent data have shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. The monitoring of biomarkers for head and neck cancer via liquid biopsy, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Role of Percutaneous Endoscopic Gastrostomy for the Nutrition of Head and Neck Cancer Patients before and up to 6 Months after Cancer Treatment.

This retrospective monocentric cohort study analyzed patients with head and neck cancer according their nutritional status and association of percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. A total of 289 patients (76.5% men; median age 62 years; 63.3% stage IV) were included. Univariate analyses and ANOVAs with repeated measures were performed to analyze differences over time. The percentage of patients requiring PEG was 14.9% (43 of 289 patients) before start of treatment (Z0), 14% (40 of 286 patients alive) after one week (Z1), 22.7% (58 of 255 patients) after six weeks (Z2) and 23% (53 of 230 patients) after six months (Z3) from the end of treatment. PEG placement was associated with alcohol or nicotine consumption, in oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impairment of food intake (all p < 0.05). Weight loss between Z1 and Z3 with PEG did not differ from patients without PEG at Z0 (p = 0.074), although patients with PEG at Z0 had a lower mean weight at the beginning. PEG was important for a quarter of the patients alive at Z3 and helped to prevent weight loss.

The Role of TGF-ß1 and Mutant SMAD4 on Epithelial-Mesenchymal Transition Features in Head and Neck Squamous Cell Carcinoma Cell Lines.

The aim of the present study was to investigate possible differences in the sensitivity of HNSCC cells to known EMT regulators. Three HNSCC cell lines (UM-SCC-1, -3, -22B) and the HaCaT control keratinocyte cell line were exposed to transforming growth factor beta 1 (TGF-ß1), a known EMT master regulator, and the cellular response was evaluated by real-time cell analysis (RTCA), Western blot, quantitative PCR, flow cytometry, immunocytochemistry, and the wound closure (scratch) assay. Targeted sequencing on 50 cancer-related genes was performed using the Cancer Hotspot Panel v2. Mutant, and wild type SMAD4 cDNA was used to generate recombinant SMAD4 constructs for expression in mammalian cell lines. The most extensive response to TGF-ß1, such as cell growth and migration, ß-actin expression, or E-cadherin (CDH1) downregulation, was seen in cells with a more epithelial phenotype. Lower response correlated with higher basal p-TGFß RII (Tyr424) levels, pointing to a possible autocrine pre-activation of these cell lines. Targeted sequencing revealed a homozygous SMAD4 mutation in the UM-SCC-22B cell line. Furthermore, PCR cloning of SMAD4 cDNA from the same cell line revealed an additional SMAD4 transcript with a 14 bp insertion mutation, which gives rise to a truncated SMAD4 protein. Overexpression of this mutant SMAD4 protein in the highly epithelial control cell line HaCaT resulted in upregulation of TGF-ß1 and vimentin. Consistent with previous reports, the invasive and metastatic potential of HNSCC tumor cells appears associated with the level of autocrine secretion of EMT regulators such as TGF-ß1, and it could be influenced by exogenous EMT cytokines such as those derived from immune cells of the tumor microenvironment. Furthermore, mutant SMAD4 appears to be a significant contributor to the mesenchymal transformation of HNSCC cells.

The Solute Carrier (SLC) Transporter Superfamily as Therapeutic Targets for the Treatment of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC.

Recurrent Versus Metastatic Head and Neck Cancer: An Evolving Landscape and the Role of Immunotherapy.

Squamous cell carcinoma of the head and neck (SCCHN) is among the ten most common cancers worldwide, with advanced SCCHN presenting with a 5-year survival of 34% in the case of nodal involvement and 8% in the case of metastatic disease. Disease-free survival at 2 years is 67% for stage II and 33% for stage III tumors, whereas 12-30% of patients undergo distant failures after curative treatment. Previous treatments often hinder the success of salvage surgery and/or reirradiation, while the standard of care for the majority of metastatic SCCHN remains palliative chemo- and immuno-therapy, with few patients eligible for locoregional treatments. The aim of this paper is to review the characteristics of recurrent SCCHN, based on different recurrence sites, and metastatic disease; we will also explore the possibilities not only of salvage surgery and reirradiation but also systemic therapy choices and locoregional treatment for metastatic SCCHN.