Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer.

Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients' nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. Method: The data of this retrospective, analytical, cohort study was collected from electronic healthcare records from the Hungarian National Health Insurance Fund Management. Overall, 38,675 HNC patients' data of the period between 2012 and 2021 was used. We applied multi-step exclusions to identify patient groups accurately and to avoid biasing factors. Statistical analysis was done by the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: Throughout the investigated period 16,871 (64%) patients received MNT therapy out of 26,253 newly diagnosed patients (≥18 years). In terms of the persistence of MNT, we divided the patients into three groups (1-3; 4-6; ≥7-month duration of MNT). When comparing these groups, we found that patients receiving long-term (≥7 months) MNT had a significantly longer overall survival (p < 0.0001) than those who received MNT for a shorter duration, both in locally advanced and recurrent/metastatic cases. Conclusion: The main outcome of the study is that there is a positive correlation between the persistence of MNT and the overall survival in HNC patients when nutritional intervention lasts several months. It highlights the responsibility of the specialists during the patient journey to use MNT early and to continue its use for as long as it is beneficial to the patients.

Tumor Seeding Post Nutritional Support Implementation: A Rare Complication; A Scoping Review.

Patients with cancer are at risk of malnutrition because of reduced food intake, thus making oral intake challenging. Thus, nutritional support is used to provide the nutrient requirements. Feeding tube site implantation among patients with cancer has been reported after endoscopic feeding gastrostomy installation. This manuscript aims to further explore this phenomenon using a structured database review. Among 33 seeding cases included in this review, case reports (70 %) were the most common study design, predominantly using percutaneous endoscopic gastrostomy via the pull method. The duration between tube implantation and seeding detection ranged from 7.12 ± 3.7 months, with some missing data among the included studies. The most common primary cancer diagnosis was head and neck cancer. Tumor seeding was higher among male patients than that in female patients. However, large-scale, statistically powered studies are needed to further investigate this complication.

Practice Patterns and Outcomes of Skin Cancer Reconstruction of the Head, Neck, and Face by Surgical Specialty: An NSQIP Analysis.

INTRODUCTION: Reconstructive procedures of the head, neck, and face after skin cancer resection are typically performed by surgeons trained in either ENT facial plastic surgery or plastic and reconstructive surgery. We analyzed a large national database to compare patient populations, practice, and outcomes of skin cancer reconstruction of the head, neck, and face performed by these 2 surgical specialties. METHODS: Cases were selected from the American College of Surgeons National Surgical Quality Improvement Program. Variables that differed significantly on univariate analysis were included in a nominal logistic regression, with having at least 1 wound-specific complication, medical complication, or unplanned reoperation within 30 days as the dependent variables. RESULTS: There were a total of 2850 cases, of which 61.36% were performed by ENT. Surgical specialty was not found to be a predictor of wound complications, medical complications, or unplanned reoperations. On multivariate analysis, operative times greater than 6 hours and anatomical location (specifically, skin cancer of the nose) predicted adverse outcomes. Significant differences were observed between the patient populations of the 2 specialties in terms of demographics, comorbidities, and the anatomical location of the cancer defect. CONCLUSION: Reconstruction of the head, neck, and face after skin cancer removal represents an important and common element in the scope of practice of both ENT facial plastic surgeons and plastic surgeons. No evidence was found to suggest that surgical specialty is associated with adverse postoperative outcomes. However, ENT facial plastic surgeons and plastic surgeons seem to manage unique patient populations and use different reconstructive techniques, reflecting their distinct training and areas of expertise. A multidisciplinary approach where the complementary skills of both specialties can be leveraged may optimize patient outcomes.

Socioeconomic Disparities in Postoperative Outcomes of Osteocutaneous Fibula Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer. METHODS: A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications. RESULTS: The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000-$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205-0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050-0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000-$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035-0.940; P = 0.042). No significant difference was found in the >$150,000 group. CONCLUSIONS: Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI.

Malnutrition in Head and Neck Free Flap Reconstruction as a Predictor of Adverse Outcomes.

INTRODUCTION: Malnutrition is associated with increased mortality in patients with head and neck (H&N) cancer. Because albumin levels are used as a surrogate for nutritional status, the purpose of this study is to assess whether malnutrition is associated with adverse postoperative outcomes in H&N free flap reconstruction. MATERIALS AND METHODS: The 2006-2018 National Surgical Quality Improvement Program Database was queried for patients undergoing flap procedures of the H&N based on Current Procedure Terminology codes. Patients were included if they were operated on by an otolaryngologist or when the primary surgical site was H&N. Nutritional status was categorized as malnourished (preoperative albumin level <3.5 g/dL) or normal (preoperative albumin level ≥3.5 g/dL). Major complications included pulmonary complications, cardiac complications, deep vein thrombosis/pulmonary embolism, and sepsis/septic shock. Minor complications included surgical infection, urinary tract infection, bleeding, and dehiscence. Data were analyzed via univariate chi-square and multivariate regression analyses. RESULTS: Of the patients, 2532 (83.3%) had normal albumin and 506 (16.7%) had hypoalbuminemia. Patients with hypoalbuminemia were more likely to have smoking history (P = 0.008), pulmonary comorbidity (P < 0.001), renal comorbidity (P = 0.018), disseminated cancer (P < 0.001), steroid use (P < 0.001), recent weight loss (P < 0.001), bleeding disorder (P = 0.023), and preoperative transfusion (P < 0.001). After adjustment for preoperative variance, malnourished patients were more likely to experience death (P < 0.001), return to operating room (P < 0.001), free flap failure (P = 0.008), pulmonary complication (P < 0.001), deep vein thrombosis/pulmonary embolism (P = 0.019), wound disruption (P = 0.042), intraoperative transfusion (P < 0.001), minor complication (P < 0.001), major complication (P < 0.001), and extended length of stay (P < 0.001). Of the patients with normal albumin, 2.1% experienced flap failure compared with 6.3% of patients with hypoalbuminemia. It should be noted that malnourished patients were 3.370 times more likely to experience flap failure (95% confidence interval, 1.383-8.212; P = 0.008) and 3.975 times more likely to experience death (95% confidence interval, 1.700-9.626; P = 0.001) than those with normal albumin. CONCLUSION: Malnutrition is associated with death, flap failure, minor complications, and other major complications following H&N free flap surgery, even after controlling for preoperative variance. Optimizing preoperative nutrition status before free flap procedures may ameliorate morbidity and mortality in H&N patients.

Correlation Between ImageJ and Conventional Manual Scoring Methods for Programmed Death-Ligand 1 Immuno-Histochemically Stained Sections.

Background: One of the most frequently used methods for quantifying PD-L1 (programmed cell death-ligand 1) expression in tumor tissue is IHC (immunohistochemistry). This may predict the patient's response to anti-PD1/PD-L1 therapy in cancer. Methods: ImageJ software was used to score IHC-stained sections for PD-L1 and compare the results with the conventional manual method. Results: In diffuse large B cell lymphoma, no significant difference between the scores obtained by the conventional method and ImageJ scores obtained using the option "RGB" or "Brightness/Contrast." On the other hand, a significant difference was found between the conventional and HSB scoring methods. ImageJ faced some challenges in analyzing head and neck squamous cell carcinoma tissues because of tissue heterogenicity. A significant difference was found between the conventional and ImageJ scores using HSB or RGB but not with the "Brightness/Contrast" option. Scores obtained by ImageJ analysis after taking images using 20 × objective lens gave significantly higher readings compared to 40 × magnification. A significant difference between camera-captured images' scores and scanner whole slide images' scores was observed. Conclusion: ImageJ can be used to score homogeneous tissues. In the case of highly heterogeneous tissues, it is advised to use the conventional method rather than ImageJ scoring.

Evaluation of a new score associated with acute kidney injury in patients treated with cisplatin based EXTREME regimen.

BACKGROUND: This study evaluates the association of diuresis and hydration through a new monitoring indicator called U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. METHODS: We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. RESULTS: Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. CONCLUSION: The combination of diuresis and i.v. hydration through the U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

Radiomic Application for Head and Neck Squamocellular Tumor: Systematic Review.

Abstract: Radiomics represents the convergence of artificial intelligence and radiological data analysis, primarily applied in the diagnosis and treatment of cancer. In the head and neck region, squamous cell carcinoma is the most prevalent type of tumor. Recent radiomics research has revealed that specific bio-imaging characteristics correlate with various molecular features of Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Human Papillomavirus (HPV). These tumors typically present a unique phenotype, often affecting younger patients, and show a favorable response to radiation therapy. This study provides a systematic review of the literature, summarizing the application of radiomics in the head and neck region. It offers a comprehensive analysis of radiomics-based studies on HNSCC, evaluating its potential for tumor evaluation, risk stratification, and outcome prediction in head and neck cancer treatment.

The potential roles of antibody-drug conjugates in head and neck squamous cell carcinoma.

PURPOSE OF REVIEW: To summarize the actual antibody-drug conjugates (ADCs) tested for patients with advanced head and neck squamous cell carcinoma (HNSCC), outlining the results of safety and efficacy through published clinical trials. RECENT FINDINGS: ADCs combine the specificity of mAbs with the cytotoxic drug (known as payload) via a chemical linker and it is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. To date, various ADCs have been investigated in multiple solid malignancies and others are in clinical development. In this study, we provide an overview of the structure and biology of ADC and we review recent clinical experience with the ADC in patients with advanced HNSCC, followed by a brief discussion of the evolvement of ADC conception, drug resistance and future perspectives. SUMMARY: ADC strategy is emerging as a potential active treatment in previously treated patients with advanced HNSCC. However, the recent improvement in the bioengineering of ADC and a better comprehension of sequencing and association strategies could provide more benefit to HNSCC patients in need of innovative therapy.

Increased V-ATPase activity can lead to chemo-resistance in oral squamous cell carcinoma via autophagy induction: new insights.

Oral squamous cell carcinoma (OSCC) is a cancer type with a high rate of recurrence and a poor prognosis. Tumor chemo-resistance remains an issue for OSCC patients despite the availability of multimodal therapy options, which causes an increase in tumor invasiveness. Vacuolar ATPase (V-ATPase), appears to be one of the most significant molecules implicated in MDR in tumors like OSCC. It is primarily responsible for controlling the acidity in the solid tumors' microenvironment, which interferes with the absorption of chemotherapeutic medications. However, the exact cellular and molecular mechanisms V-ATPase plays in OSCC chemo-resistance have not been understood. Uncovering these mechanisms can contribute to combating OSCC chemo-resistance and poor prognosis. Hence, in this review, we suggest that one of these underlying mechanisms is autophagy induced by V-ATPase which can potentially contribute to OSCC chemo-resistance. Finally, specialized autophagy and V-ATPase inhibitors may be beneficial as an approach to reduce drug resistance to anticancer therapies in addition to serving as coadjuvants in antitumor treatments. Also, V-ATPase could be a prognostic factor for OSCC patients. However, in the future, more investigations are required to demonstrate these suggestions and hypotheses.

Single-cell RNA sequencing explores the evolution of the ecosystem from leukoplakia to head and neck squamous cell carcinoma.

It has been found that progression from leukoplakia to head and neck squamous cell carcinoma (HNSCC) is a long-term process that may involve changes in the multicellular ecosystem. We acquired scRNA-seq samples information from gene expression omnibus and UCSC Xena database. The BEAM function was used to construct the pseudotime trajectory and analyze the differentially expressed genes in different branches. We used the ssGSEA method to explore the correlation between each cell subgroup and survival time, and obtained the cell subgroup related to prognosis. During the progression from leukoplakia to HNSCC, we found several prognostic cell subgroups, such as AURKB + epithelial cells, SFRP1 + fibroblasts, SLC7A8 + macrophages, FCER1A + CD1C + dendritic cells, and TRGC2 + NK/T cells. All cell subgroups had two different fates, one tending to cell proliferation, migration, and enhancement of angiogenesis capacity, and the other tending to inflammatory immune response, leukocyte chemotaxis, and T cell activation. Tumor-promoting genes such as CD163 and CD209 were highly expressed in the myeloid cells, and depletion marker genes such as TIGIT, LAG3 were highly expressed in NK/T cells. Our study may provide a reference for the molecular mechanism of HNSCC and theoretical basis for the development of new therapeutic strategies.

The effect of physical exercise during radiotherapy on physical performance in patients with head and neck cancer: a trial within cohorts study protocol, the vital study.

BACKGROUND: During the last decade, twelve studies have been published investigating physical exercise interventions (PEIs) in patients with head and neck cancer (HNC) during radiotherapy (RT), chemoradiation (CRT) or bioradiation (BRT). These studies showed that these PEIs are safe and feasible. However, only two of these studies were randomised clinical trials (RCTs) with a satisfying sample size. Thereby, there is no cost-effectiveness study related to a PEI during RT, CRT or BRT ((C/B)RT) for patients with HNC. Therefore, the aim of this study is to investigate and compare physical performance, muscle strength, fatigue, quality of life (QoL), body mass index (BMI), nutritional status, physical activity, treatment tolerability, and health care related costs in patients with HNC with and without a 10 week PEI during (C/B)RT. METHODS: This study, based on a trial within cohorts (TwiCs) design, will contain a prospective cohort of at least 112 patients. Fifty-six patients will randomly be invited for an experimental 10 week PEI. This PEI consists of both resistance and endurance exercises to optimize physical performance, muscle strength, fatigue, QoL, BMI, nutritional status, physical activity, and treatment tolerability of (C/B)RT. Measurements are at baseline, after 12 weeks, 6 months, and at 12 months. Statistical analyses will be performed for intention-to-treat and instrumental variable analysis. DISCUSSION: This study seeks to investigate physical, QoL, and economic implications of a PEI. With a substantial sample size, this study attempts to strengthen and expand knowledge in HNC care upon PEI during (C/B)RT. In conclusion, this study is dedicated to provide additional evidence for PEI in patients with HNC during (C/B)RT. TRIAL REGISTRATION: protocol was registered at clinicaltrials.gov with number NCT05988060 on 3 August 2023.

Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).

The complex evolution of genetic alterations in cancer that occurs in vivo is a selective process involving numerous factors and mechanisms. Chemotherapeutic agents that prevent the growth and spread of cancer cells induce selective pressure, leading to rapid artificial selection of resistant subclones. This rapid evolution is possible because antineoplastic drugs promote alterations in tumor­cell metabolism, thus creating a bottleneck event. The few resistant cells that survive in this new environment obtain differential reproductive success that enables them to pass down the newly selected resistant gene pool. The present review aims to summarize key findings of tumor evolution, epithelial­mesenchymal transition and resistance to cetuximab therapy in head and neck squamous cell carcinoma.

The role of ferroptosis in radiotherapy and combination therapy for head and neck squamous cell carcinoma (Review).

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive, heterogeneous tumour usually caused by alcohol and tobacco consumption, making it one of the most common malignancies worldwide. Despite the fact that various therapeutic approaches such as surgery, radiation therapy (RT), chemotherapy (CT) and targeted therapy have been widely used for HNSCC in recent years, its recurrence rate and mortality rate remain high. RT is the standard treatment choice for HNSCC, which induces reactive oxygen species production and causes oxidative stress, ultimately leading to tumour cell death. CT is a widely recognized form of cancer treatment that treats a variety of cancers by eliminating cancer cells and preventing them from reproducing. Immune checkpoint inhibitor and epidermal growth factor receptor are important in the treatment of recurrent or metastatic HNSCC. Iron death, a type of cell death regulated by peroxidative damage to phospholipids containing polyunsaturated fatty acids in cell membranes, has been found to be a relevant death response triggered by tumour RT in recent years. In the present review, an overview of the current knowledge on RT and combination therapy and iron death in HNSCC was provided, the mechanisms by which RT induces iron death in tumour cells were summarized, and therapeutic strategies to target iron death in HNSCC were explored. The current review provided important information for future studies of iron death in the treatment of HNSCC.

Human papillomavirus, oropharyngeal cancer, and the latest vaccine: considerations for oral healthcare providers.

Human papillomavirus (HPV) is associated with both benign and malignant disorders, such as genital warts and a variety of cancers, including oropharyngeal squamous cell carcinomas (OPSCCs). The current 9-valent HPV vaccine (Gardasil 9) protects against high-risk strains that have been shown to cause OPSCC, and widespread vaccination should reduce the rate of all HPV-associated cancers. HPV-related OPSCCs differ from non-HPV-related OPSCCs in their clinical presentations and responsiveness to treatment. To provide oral healthcare providers with a basis for effective com-munication with patients, this article will examine the evolution of the HPV vaccination schedule and the role of the HPV vaccine in the prevention of OPSCCs.

Identification of two distinct head and neck squamous cell carcinoma subtypes based on fatty acid metabolism-related signatures: Implications for immunotherapy and chemotherapy.

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.