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.

Head and neck cancer (HNC) represents a significant global health challenge, with over 660,000 annual diagnoses and a mortality rate exceeding 49 %, making it the seventh most common cancer worldwide. Current standard treatments, including surgery, radiation, and chemotherapy, often result in significant side effects, underscoring the need for innovative and personalized therapeutic approaches. In recent years, botulinum toxin (BoNT) has emerged as a transformative adjunctive therapy in HNC management. Initially recognized for its neuromuscular blocking properties, BoNT has expanded its applications to alleviate complications such as sialorrhea, gustatory sweating, and neuropathic pain associated with HNC treatment. Beyond symptomatic relief, emerging evidence suggests that BoNT may influence tumor biology by modulating the tumor microenvironment, disrupting nerve-cancer interactions, and altering key molecular pathways to inhibit tumor growth and metastasis. This article explores BoNT's achievements and therapeutic potential in treating HNC, examining its molecular mechanisms, clinical efficacy, and implications for future research. By elucidating BoNT's role in symptom management and its potential as an anti-tumor agent, this review highlights a promising avenue for advancing personalized medicine and improving outcomes for HNC patients.

Advances in the field of nanomaterials are laying the foundation for the fabrication of nanosensors that are sensitive, selective, specific, cost-effective, biocompatible, and versatile. Being highly sensitive and selective, nanosensors are crucial in detecting small quantities of analytes and early diagnosis of diseases. These devices, operating on the nanoscale, detect signals, such as physical, chemical, optical, electrochemical, or biological, and then transduce them into a readable form. They show great promise for real-time, point-of-care, and home-based applications in health care. With the integration of wireless technology, these nanosensors, specifically biosensors, can potentially revolutionize therapeutic techniques. These advancements particularly impact the oral cavity, the primary entry point for various bodily substances. Nanosensors can transform oral and dental health practices, enabling timely disease diagnosis and precise drug delivery. This review examines the recent advancements in nanobiosensors, exploring their applications in various oral health conditions while discussing their benefits and potential limitations.

Oral health is intricately related to systemic health, with new worldwide research demonstrating vitamin D's critical role in sustaining dental and periodontal health. Vitamin D regulates calcium and phosphate metabolism, which is required for the formation and maintenance of healthy teeth and bones. According to research, vitamin D deficiency may contribute to the etiology of periodontal disease by decreasing the host immune response, making it more susceptible to infections like gingivitis and periodontitis. Oral health in India is a tapestry of traditional practices, socioeconomic factors, lifestyle factors, and access to modern healthcare, all of which are intricately linked with the concept of habitus, which refers to deeply embedded habits, dispositions, and practices shaped by an individual's social space. Deep-rooted social and cultural influences have a substantial impact on oral hygiene practices, food patterns, and health-seeking behaviours. Oral diseases are considered as a worldwide health issue. Though standard Western medicine has had effectiveness in preventing and treating periodontal diseases and other oral disorders, the hunt for alternative solutions continues, and natural phytochemicals extracted from plants used in traditional medicine are regarded as viable alternatives to synthetic chemicals. India's traditional medical knowledge and practice, take a comprehensive approach to oral health, emphasizing the balance of physiological components and the use of natural treatments to maintain oral hygiene and treat oral disorders. However, the structural integrity of teeth and optimal oral health can be accomplished by combining Indian traditional medical practices with vitamin D supplementation, which has synergistic attributes for gum health, anti-inflammatory effects, and dental caries prevention. Nevertheless, the unique association of oral health, vitamin D deficiency and the habitus from Indian perspective is extremely underrepresented in academia. To the best of our knowledge, in the aforementioned context, the present narrative review is probably the maiden attempt to discern the crosstalk of oral health and Vitamin D from the perspectives of Indian habitus.

The tumor microenvironment (TME) plays a crucial role in the development, progression, and metastasis of oral squamous cell carcinoma (OSCC). The TME comprises various cellular and acellular components, including immune cells, stromal cells, cytokines, extracellular matrix, and the oral microbiome, all of which dynamically interact with tumor cells to influence their behavior. Immunosuppression is a key feature of the OSCC TME, with regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) contributing to an environment that allows tumor cells to evade immune surveillance and supports angiogenesis. The oral microbiome also plays a pivotal role in OSCC pathogenesis, as dysbiosis, or imbalances in the microbiota, can lead to chronic inflammation, which promotes carcinogenesis through the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum have, hence, been implicated in OSCC-driven tumor progression, as they induce inflammation, activate oncogenic pathways, and modulate immune responses. In this review, we discuss how the interplay between immunosuppression and microbiome-driven inflammation creates a tumor-promoting environment in OSCC, leading to treatment resistance and poor patient outcomes, and explore the potential therapeutic implication of a better understanding of OSCC etiology and molecular changes.

Head and neck squamous cell carcinoma (HNSCC) is a major global health burden, often associated with poor prognosis and limited therapeutic options. Long non-coding RNAs (lncRNAs), a diverse group of non-coding RNA molecules > 200 nucleotides in length, have emerged as critical regulators in the pathogenesis of HNSCC. This review summarizes the mechanisms through which certain lncRNAs regulate chromatin modification, mRNA splicing, and interactions with RNA-binding proteins and contribute to the development and progression of HNSCC. Interaction of lncRNAs with key oncogenic pathways, such as PI3K/AKT and Wnt/β-catenin, highlights their importance in tumor progression. The role of lncRNAs, such as ELDR, MALAT1, NEAT1, HOTAIR, and UCA1, which promote cell proliferation, metastasis, immune evasion, and therapy resistance is discussed. Moreover, several lncRNAs are being evaluated in clinical trials for their potential as biomarkers, reflecting their clinical significance. We further address the challenges and opportunities for targeting lncRNA therapeutically, highlighting the promise of lncRNA-based interventions for personalized cancer treatment. Gaining insight into the function of lncRNAs in HNSCC could pave the way for novel therapeutic strategies to potentially improve patient outcomes.

It is well known that a number of head and neck carcinomas are associated with HRAS mutations, and that several cancers with RAS mutations, such as lung cancer, have a poor prognosis. In this study, we evaluated the frequency of HRAS mutations in head and neck carcinomas and characterized the clinical and cell biological features of carcinomas with HRAS mutations. HRAS mutations at codons 12, 13, and 61, mutational hot spots, were evaluated in tissue specimens obtained from 119 Japanese patients treated at our institution. DNA was successfully extracted from 100 specimens, and sequencing was completed. An HRAS mutation was found in 8 (8.0%) cases: 5 (6.1%) out of 82 HNSCCs and 3 (16.7%) out of 18 salivary gland carcinomas. Mutations were found at codons 12 and 61, while none were found at codon 13, which differs from previous reports. The mutation-positive cases had a relatively poor prognosis, consistent with previous reports, and were more frequently accompanied by distant metastasis. HRAS knockdown with siRNA suppressed the in vitro migration ability of HRAS mutation-positive cells but not that of HRAS mutation-negative cells. In conclusion, a positive HRAS mutation could be an indicator of distant metastasis and poor prognosis, as well as a potential therapeutic target.

Background/Objectives: Vitamin D is classically associated with calcium and phosphate homeostasis, but recent research has expanded its role to include several new roles such as immune regulation, inflammation, and potential anti-cancer properties. The vitamin D receptor (VDR) is expressed in over 400 tissues, including those of the head and neck, implying a potential link between vitamin D and head and neck cancers (HNCs). Given the need for newer and better therapeutic approaches, this systematic review aims to synthesize existing clinical evidence on the relationship between vitamin D status and clinical outcomes in HNC patients. Methods and Results: A comprehensive literature search, across multiple databases including PubMed, Google Scholar and Science Direct, identified 187,642 studies related to vitamin D and cancer, from which 16 studies met the inclusion criteria. The inclusion criteria were English-language, full-text original research (2015-2025) on vitamin D's role in HNC progression and treatment, focusing on human studies. The findings indicate that vitamin D deficiency is highly prevalent among HNC patients, with rates ranging from 47% to 95%, particularly in advanced-stage cancers and those undergoing intensive treatment. Inverse association between vitamin D levels and HNC risk was reported, with higher serum 25(OH)D levels linked to a 30-32% reduction in cancer risk. Additionally, higher vitamin D levels correlated with improved survival rates and reduced recurrence, though some findings lacked statistical significance. Deficiencies were associated with higher rates of malnutrition and postoperative complications, reinforcing vitamin D's role in nutritional stability and surgical recovery. Conclusions: This systematic review highlights how common and significant vitamin D deficiency is among head and neck cancer (HNC) patients, exploring its possible role in cancer risk, prognosis, survival, treatment-related side effects, malnutrition, and post-surgical complications. The evidence suggests that while higher vitamin D levels are linked to better survival and fewer treatment-related issues, the benefits seem to level off beyond a certain point, indicating a more complex relationship. Additionally, vitamin D supplementation appears to help reduce chemoradiation side effects like mucositis, skin toxicity, dysphagia, and pain, ultimately improving patients' quality of life during treatment.

This study aimed to explore the disparities in PD-1 and PD-L1 expression among oral squamous cell carcinomas (OSCCs) in individuals categorized as never-smokers/never-drinkers versus smokers/drinkers.

Immunohistochemical staining for PD-1 and PD-L1, along with PDCD1LG2/cen9 dual color probe analysis, was conducted on 130 OSCC specimens from both smoker/drinker and never-smoker/never-drinker cohorts. Associations between smoking/drinking status, clinicopathologic data, immunohistochemical antibody expression, fluorescence in situ hybridization, and survival outcomes were assessed.

OSCC in never-smokers/never-drinkers exhibited significantly elevated PD-1 expression (p = 0.003), increased PD-L1-TPS expression (p = 0.044), and elevated PD-L1-CPS expression (p < 0.001). High PD-L1-ICS expression was more prevalent in never-smokers (p = 0.042). Moreover, never-smokers and never-drinkers demonstrated augmented PD-L1 gene copy numbers (p = 0.081 and p = 0.054, respectively). Increased PD-L1 gene copy number, particularly amplification, correlated with PD-L1-TPS (p = 0.039 and p < 0.001). Conversely, PD-L1 gene copy loss was associated with negative PD-L1-CPS (p = 0.023). Notably, positive PD-L1-CPS was significantly linked with improved overall survival (p = 0.023).

OSCC arising in never-smokers/never-drinkers exhibit heightened PD-1/PD-L1 signaling, suggesting potential efficacy of immune checkpoint therapy in this subgroup of tumors.

The aim of this study is to introduce a new modification of fasciomyocutaneus infrahyoid flap with increased volume and longer durability to reduce the need for free flaps in reconstructions after oral tongue cancer surgeries.

Patients with advanced oral tongue cancers, especially those with base of tongue involvement, who traditionally required free flap reconstruction due to the large defects after resection, were included in the study. The large tongue defects were reconstructed using entire thyroid lobe on the tumor side as part of our new modification of the infrahyoid flap.

In patients reconstructed with the modified infrahyoid flap, none showed evidence of necrosis or complications such as flap atrophy after surgery or over time.

Inclusion of the tumor-side thyroid lobe in the infrahyoid flap provides additional volume compared to previous modifications, potentially leading to more widespread use of this flap in oncological surgeries of the oral tongue. Furthermore, this technique may reduce the need for free flaps in more advanced stages, offering a less invasive and more accessible option for reconstructive surgeries.

In recent years, immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced malignancies. As such, numerous ICIs are establishing themselves as prospective therapy alternatives for individuals with head and neck cancer (HNC). Evidence suggests a potential correlation between body mass index (BMI) and the efficacy of ICIs in cancer patients. However, this association in HNC patients subjected to immunotherapy is still unclear.

To investigate the effect of BMI on the survival outcomes of HNC patients treated with immunotherapy.

PubMed, Web of Science, and Google Scholar databases were searched extensively for records published until January 2024. Full-text articles aligned with the research objective were included, while records published in English, case reports, reviews, editorials, and studies reporting immunotherapy combined with other cancer therapies were excluded. The data required for review and analysis was abstracted in Excel files by two independent reviewers. Additionally, data synthesis was carried out using the Review Manager program, and evaluation of methodological quality was done with the Newcastle Ottawa scale. The statistical analyses were stratified according to the BMI values, of which patients were categorized as follows: Obese (BMI ≥ 27.5), non-obese (BMI < 27.5), overweight (BMI: 23.5-27.5), underweight (BMI < 18.5), normal (BMI: 18.5-23.5), low (BMI < 20), and high (BMI ≥ 20).

Only six studies were reviewed and analyzed. A subgroup analysis of data from these studies showed that obese HNC patients on immunotherapy had significantly better overall survival (OS) rates than non-obese patients (HR: 0.51; 95% CI: 0.29-0.93; p = 0.03). However, the progression-free survival (PFS) was statistically similar between obese and non-obese patients (HR: 0.72; 95% CI: 0.39-1.33; p = 0.30). In addition, when BMI was stratified as either low or high, no significant difference was observed in the OS and PFS of HNC patients (HR: 0.99; 95% CI: 0.59-1.66; p = 0.97 and HR: 0.93; 95% CI: 0.61-1.41; p = 0.42, respectively). Similarly, the statistical analyses showed that overweight patients have similar OS and PFS as patients with normal BMI (HR: 0.53; 95% CI: 0.15-1.92; p = 0.33 and HR: 0.55; 95% CI: 0.20-1.52; p = 0.25, respectively). In contrast, underweight patients demonstrated poor OS and PFS (HR: 2.56; 95% CI: 1.29-5.12; p = 0.008 and HR: 2.76; 95% CI: 1.17-6.52; p = 0.02, respectively).

Obese HNC patients on immunotherapy tend to have improved OS than non-obese patients, while underweight patients have worse clinical prognoses than those with normal or above BMI.

The relations between coffee and tea consumption and head and neck cancer (HNC) incidence are unclear. With increasing global HNC burden, this study aims to examine the association between coffee, tea, and HNC.

A pooled analysis of 9548 HNC cases and 15,783 controls from 14 individual-level case-control studies was conducted from the International Head and Neck Cancer Epidemiology consortium. Random-effects logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for HNC and its subsites, adjusting for sociodemographic and lifestyle factors.

Compared to non-coffee drinkers, drinking >4 cups of caffeinated coffee daily was inversely associated with HNC (OR, 0.83; 95% CI, 0.69-1.00), oral cavity (OR, 0.70; 95% CI, 0.55-0.89), and oropharyngeal cancers (OR, 0.78; 95% CI, 0.61-0.99). Drinking 3-4 cups of caffeinated coffee was inversely associated with hypopharyngeal cancer (OR, 0.59; 95% CI, 0.39-0.91). Drinking decaffeinated coffee and drinking between >0 to <1 cup daily were inversely associated with oral cavity cancer (OR, 0.75; 95% CI, 0.64-0.87 and OR, 0.66; 95% CI, 0.54-0.81). Drinking tea was inversely associated with hypopharyngeal cancer (OR, 0.71; 95% CI, 0.59-0.87). Daily tea consumption of >0 to ≤1 cup was inversely associated with HNC (OR, 0.91; 95% CI, 0.84-0.98) and hypopharyngeal cancer (OR, 0.73; 95% CI, 0.59-0.91), but drinking >1 cup was associated with laryngeal cancer (OR, 1.38; 95% CI, 1.09-1.74).

These findings support reduced HNC risk among coffee and tea drinkers. Future studies are needed to address geographical differences in types of coffee and tea to improve our understanding of the association of coffee and tea and global HNC risk.

The Naples prognostic score (NPS) and its relation to the prognosis of oral squamous cell carcinoma (OSCC) have been inconclusive. This study aimed to investigate the correlation between NPS and the prognosis of postoperative OSCC patients. Additionally, the study sought to develop a new nomogram for predicting disease-free survival (DFS) and overall survival (OS).

The study included 576 OSCC patients who underwent surgical treatment at two hospitals between August 2008 and June 2018. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors. Subsequently, two nomograms were developed to predict DFS and OS based on these factors and underwent rigorous validation.

The median DFS and OS were 31.5 months and 36.5 months, respectively. Significant differences in DFS and OS were observed among patients with different NPS scores. Adjuvant radiotherapy, age-adjusted Charlson comorbidity index (ACCI), extranodal extension (ENE), NPS, American Joint Committee on Cancer (AJCC) stage, surgical safety margin, eastern cooperative oncology group performance status (ECOG PS), and systemic inflammation score (SIS) were identified as independent predictors of DFS and OS. In the training cohort, the nomogram's concordance index (C-index) for predicting DFS and OS was 0.701 and 0.693, respectively. In the validation group, the corresponding values were 0.642 and 0.635, respectively. Calibration plots confirmed a high level of agreement between the model's predictions and actual outcomes. Decision curve analysis (DCA) demonstrated the nomogram's good clinical utility. Additionally, patients in the low-risk group did not benefit from adjuvant radiotherapy, while those in the medium-risk and high-risk group could benefit from adjuvant radiotherapy.

NPS significantly influences the prognosis of OSCC patients following surgery. The nomogram developed in this study holds significant clinical application potential. The low-risk subgroup of patients was not required to undergo postoperative radiotherapy.

Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.

Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.

Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.

SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.

This study aims to elucidate the therapeutic efficacy and safety of a taxane-based chemotherapy in combination with immune checkpoint inhibitors regimen in patients diagnosed with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

We retrospectively collected clinical data from 154 patients who received at least two cycles of PD-1 inhibitors in combination with a taxane-based chemotherapy as first-line treatment in seven hospitals in Hunan Province, between December 2018 and December 2023. These patients were subjected to long-term follow-up.

The study included 154 eligible patients, with a median follow-up period of 21.5 months. The median PFS was 8.7 months, while the median OS was 16.7 months. The 12-month PFS rate was 43.6%, and the 12-month OS rate was 60.1%. At 24 months, the PFS rate was 34.4%, and the OS rate was 36.9%. With 26 complete responses (16.9%) and 52 partial responses (33.8%), the ORR was 50.6%. Stable disease was observed in 54 patients (35.1%), resulting in a disease control rate of 85.7%, while 22 patients showed progressive disease. In the univariate analysis, the distant organ metastasis had a statistically significant impact on both PFS and OS. Subsequent radiotherapy following this protocol also showed a statistically significant effect on PFS and OS. However, radiotherapy before recurrent metastasis did not significantly affect PFS, though it did have a significant impact on OS. Other factors analyzed did not show a statistically significant effect on PFS and OS. Multivariate analysis indicated that the distant organ metastasis and subsequent radiotherapy following this protocol were independent prognostic factors for PFS in patients with R/M HNSCC, and the latter was also an independent prognostic factor for OS in these patients. Regarding safety, during treatment anemia was observed in 97 patients, leukopenia in 64, neutropenia in 33, thrombocytopenia in 28, transaminase elevation in 46, hypothyroidism in 46 patients, and one patient stopped taking the medication due to a serious adverse reaction. No treatment-related deaths occurred.

The combination of PD-1 inhibitors with a a taxane-based chemotherapy regimen as a first-line treatment for R/M HNSCC patients demonstrates good therapeutic efficacy and acceptable safety profiles.

Oral squamous cell carcinoma (OSCC) is a multifactorial malignancy influenced by various genetic and environmental factors. Tobacco habits, human papilloma virus (HPV) infection, and p53 polymorphisms or mutations have been implicated in its etiology. Understanding their interplay can provide insights into OSCC risk assessment.

A case-control study was conducted among 300 OSCC patients and 300 age- and sex-matched controls. Data on tobacco use (smoking and smokeless), HPV infection status (detected via PCR), and p53 polymorphism/mutation (analyzed by sequencing) were collected. Statistical analysis included logistic regression to assess the associations and interactions among these variables.

Among OSCC cases, 75% were tobacco users compared to 35% in controls. HPV prevalence was significantly higher in OSCC cases (30%) than controls (5%). P53 mutations were identified in 40% of OSCC cases compared to 10% in controls. Logistic regression revealed synergistic effects between tobacco use and HPV infection (OR 5.2, 95% CI 3.0-9.0) and additive effects with p53 mutations (OR 3.5, 95% CI 2.0-6.0).

Tobacco habits, HPV infection, and p53 polymorphisms/mutations independently and synergistically contribute to the risk of OSCC. Strategies focusing on tobacco cessation, HPV vaccination, and genetic screening may help mitigate OSCC risk in susceptible populations.

Oral cancer remains a persistent health challenge globally, with rising incidence and flat survival rates, particularly among disadvantaged populations. This paper explores the socioeconomic, ethnic and cultural factors contributing to inequalities in oral cancer care, such as limited access to healthcare, lower education levels, financial constraints and systemic disadvantages based on ethnicity and cultural practices. Addressing these inequalities requires a multi-faceted approach, including community outreach, patient education and policy advocacy.Effective strategies include mobile clinics, free screening events, culturally sensitive educational materials, digital tools and social media outreach. Integrating telehealth services, artificial intelligence for early diagnosis, community-based participatory research and microfinance initiatives are also crucial. Furthermore, improving health literacy and promoting preventive behaviours are essential steps towards mitigating these inequalities.Public health education and social services must collaborate to enhance access to dental care, ensuring better outcomes across all populations, regardless of socioeconomic or ethnic background. This paper highlights the role of dental professionals in reducing inequalities and promoting oral health equity through innovative and comprehensive strategies.

Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up.

Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations.

In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively.

After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC.

NCT02358031.

Liquid biopsy is gaining momentum for diagnosis and surveillance of cancer patients. Indeed, head and neck squamous cell carcinoma (HNSCC) is burdened with poor prognosis and high recurrence rates after treatment. It is therefore crucial to be able to detect minimal residual disease early after radical treatment or relapse, so surgery can be performed when the disease is still resectable. In this scenario, aim of this study is to create a liquid biopsy-based pipeline able to detect somatic tumor mutations in a cohort of HNSCC-affected patients undergoing follow-up after surgical intervention.

Our cohort included 17 patients diagnosed with HNSCC over 4 years. The first saliva sample was collected before surgery while the rest were collected during the subsequent visits, according to the follow-up schedule. Salivary DNA (sDNA) was extracted, and a 52-gene next generation sequencing (NGS)-based panel was used for somatic variants detection.

41.2% of samples collected before surgery bore a deleterious variant (n=7/17). Overall, 29.2% of samples harbored at least a pathogenic variant (n=21/72). The most frequently mutated genes were TP53 (80%), FBXW7 (8%), PDGFRA (4%) and PTEN (4%). Finally, three patients experienced a loco-regional relapse by clinical evaluations, anticipated in 67% of cases by the molecular one (n=2/3).

Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.

To depict the current state of global surgery opportunities in United States ACGME-approved Otolaryngology residency programs and compare the characteristics of programs with and without these opportunities.

In this cross-sectional analysis, websites of ACGME-accredited Otolaryngology residency programs were analyzed for information on program size, rank, age, and geographic region as obtained through the Doximity platform in 2023. Additional parameters were obtained for programs listing global surgery opportunities such as funding, faculty oversight, location/region, focus, and relationship to the community served. Data were tabulated and analyzed in Microsoft Excel and Stata.

Of the 131 ACGME-accredited Otolaryngology residency programs, 26 (20%) of programs advertised a global surgery opportunity. Nine (35%) of these promoted funding, 15 (58%) offered a clinical focus, one (4%) offered a research focus, and 10 (38%) offered a combined approach. The Midwest region had the most programs with global surgery opportunities (n = 8, 31%). Less than half (42%) of programs had an established partnership with local partners within low and middle-income countries (LMICs). When comparing programs, the average Doximity rank, average program age, and average program size of programs that offered global surgery opportunities was significantly higher than those that did not (37.2 vs. 71.5, 54 vs. 41, 19.5 vs. 13.7; all p < 0.05).

Approximately one-fifth of Otolaryngology training programs have a global surgery opportunity. Programs that offer these opportunities had a higher Doximity ranking, older program age, and a larger trainee cohort. These results highlight potential areas for expanding global surgery opportunities in academic institutions.

NA Laryngoscope, 134:4501-4505, 2024.

To investigate the clinical efficacy, preservation of laryngeal function, and safety differences between PD-1 inhibitors combined with chemotherapy, and targeted therapy combined with chemotherapy in LA HPSCC patients.

This was a retrospective analysis of patients with LA HPSCC treated at Beijing Tongren Hospital, Capital Medical University from October, 2020 to March, 2024. A total of 110 eligible patients were included, 56 in the PD-1 inhibitors combined with chemotherapy group (Group A), and 54 in the targeted therapy combined with chemotherapy group (Group B). Relevant clinical data were collected, and the clinical efficacy, preservation of laryngeal function, complete response (CR) rate, pathological complete response (pCR) rate, major pathological response (MPR), and treatment-related adverse events (TRAEs) of the two groups were analyzed and compared.

In both groups A and B, the objective response rate (ORR) and disease control rate (DCR) were similar with no significant differences, but the pCR rate in Group A was much higher than that in Group B, at 37.5% and 7.4%, respectively (p<0.001). The rate of primary tumor downstaging in group A was much higher than that in group B (76.8% vs. 38.9%) as well (p<0.0001). In addition, the 1y-OS rate in group A was 95.7%, compared to 87.0% in group B (p=0.106, HR=0.34; 95% CI: 0.114-1.013), and the 1y-PFS rate was 89.4% in group A compared to 85.2% in group B (p=0.399, HR=0.675; 95% CI: 0.275-1.659). Furthermore, the larynx function preservation rate was significantly higher in group A at 85.7%, compared to that of group B at only 66.7% (p=0.019). There were no deaths due to TRAEs in either group, and there was no significant difference in the incidence of grade 3-4 TRAEs between the two groups either (p=0.77). The main TRAEs in Group A were metabolism and nutrition disorders (52/56, 92.9%) and, in Group B were blood and lymphatic system disorders (40/54, 74.1%).

PD-1 inhibitors combined with chemotherapy showed better short-term efficacy compared to targeted therapy. Additionally, a trend toward improved long-term survival was observed with PD-1 inhibitors but not with targeted therapy. Results for both groups indicate that neoadjuvant therapy is both safe and manageable.

While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR  = 2.12, 95% CI: 1.24-3.61; χ2  = 7.71; ROR  = 2.19, 95% CI: 1.24-3.86; IC  = 1.01; IC025  = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR  = 0.38, 95% CI: 0.19-0.73) and pembrolizumab (OR  = 0.48, 95% CI: 0.23-0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR  = 3.04, 95% CI: 1.73-5.31; χ2  = 16.13; ROR  = 3.15, 95% CI: 1.74-5.70; IC  = 1.46; IC025  = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR  = 0.25, 95% CI: 0.13-0.48) and pembrolizumab (OR  = 0.40, 95% CI: 0.20-0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR  = 0.61, 95% CI: 0.38-0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR  = 3.72, 95% CI: 1.87-7.43; χ2  = 15.99; ROR  = 3.75, 95% CI: 1.87-7.51; IC  = 1.53, IC025  = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR  = 0.09, 95% CI: 0.09-0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR  = 1.27, 95% CI: 1.05-1.53; χ2  = 6.38; ROR  = 1.28, 95% CI: 1.06-1.56; IC  = 0.29, IC025  = -0.00) and pembrolizumab (PPR  = 2.20, 95% CI: 1.79-2.71; χ2  = 56.55; ROR  = 2.31, 95% CI: 1.84-2.88; IC  = 1.03; IC025  = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR  = 0.58, 95% CI: 0.44-0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

Sarcopenia is recognized as a crucial factor impacting the prognosis, treatment responses, and quality of life of HNC patients. This review discusses various mechanisms, including common etiological factors, such as aging, chronic inflammation, and metabolic dysregulation. Cancer-related factors, including tumor locations and treatment modalities, contribute to the development of sarcopenia. The clinical implications of sarcopenia in HNC patients extend beyond reduced muscle strength; it affects overall mobility, reduces quality of life, and increases the risk of falls and fractures. Sarcopenia serves as an independent predictor of postoperative complications, chemotherapy dose-limiting toxicity, and treatment outcomes, which affect therapy planning and perioperative management decisions. Methods to assess sarcopenia in HNC patients encompass various techniques. A sarcopenia assessment offers a potentially efficient and readily available tool for clinical practice. Interventions and management strategies for sarcopenia involve exercise interventions as a cornerstone; however, challenges arise due to patient-specific limitations during cancer treatment. A routine body composition analysis is proposed as a valuable addition to HNC patient management, with ongoing research required to refine preoperative exercise and nutrition programs for improved treatment outcomes and survival.

Head and neck (HnN) cancers are among the most common cancers in the world. Proton therapy (PT) is one of the latest advancements in the treatment modalities of cancers. Proton therapy is specifically used to treat HnN cancer patients due to its less toxic effects on the surrounding critical structures. Keeping in view the opportunities for further advancements, there is a lot of literature covering PT in HnN cancer patients. However, few compiled studies are not enough to compare the toxicities, overall survival (OS), local control (LC), and quality of life (QoL) of PT with that of intensity-modulated radiation therapy (IMRT). The objective of this review is to compile and summarize the literature available on the toxicities, OS, LC, and QoL in HnN cancer patients post PT. We have gathered and summarized the literature found under the keyword "proton therapy for head and neck cancers". Proton therapy is a preferable option over IMRT because it isolates tumors of the HnN, reduces exposure of healthy cells to radiation, and allows accurate tumor scanning using the pencil beam technique. In view of this article, we can say that PT is a preferable mode of radiotherapy for HnN cancer patients in view of its accuracy and lower incidents of acute and late toxicities.

Intratumoral hypoxia not only promotes angiogenesis and invasiveness of cancer cells but also creates an immunosuppressive microenvironment that facilitates tumor progression. However, the mechanisms by which hypoxic tumor cells disseminate immunosuppressive signals remain unclear. In this study, we demonstrate that a hypoxia-induced long noncoding RNA HIF1A Antisense RNA 2 (HIF1A-AS2) is upregulated in hypoxic tumor cells and hypoxic tumor-derived exosomes in head and neck squamous cell carcinoma (HNSCC). Hypoxia-inducible factor 1 alpha (HIF1α) was found to directly bind to the regulatory region of HIF1A-AS2 to enhance its expression. HIF1A-AS2 reduced the protein stability of major histocompatibility complex class I (MHC-I) by promoting the interaction between the autophagy cargo receptor neighbor of BRCA1 gene 1 (NBR1) protein and MHC-I, thereby increasing the autophagic degradation of MHC-I. In HNSCC samples, the expression of HIF1A-AS2 was found to correlate with hypoxic signatures and advanced clinical stages. Patients with high HIF1α and low HLA-ABC expression showed reduced infiltration of CD8+ T cells. These findings define a mechanism of hypoxia-mediated immune evasion in HNSCC through downregulation of antigen-presenting machinery via intracellular or externalized hypoxia-induced long noncoding RNA.

Previous studies have demonstrated that genetic alterations governing epigenetic processes frequently drive tumor development and that modifications in RNA may contribute to these alterations. In the 1970s, researchers discovered that N6-methyladenosine (m6A) is the most prevalent form of RNA modification in advanced eukaryotic messenger RNA (mRNA) and noncoding RNA (ncRNA). This modification is involved in nearly all stages of the RNA life cycle. M6A modification is regulated by enzymes known as m6A methyltransferases (writers) and demethylases (erasers). Numerous studies have indicated that m6A modification can impact cancer progression by regulating cancer-related biological functions. Tumor angiogenesis, an important and unregulated process, plays a pivotal role in tumor initiation, growth, and metastasis. The interaction between m6A and ncRNAs is widely recognized as a significant factor in proliferation and angiogenesis. Therefore, this article provides a comprehensive review of the regulatory mechanisms underlying m6A RNA modifications and ncRNAs in tumor angiogenesis, as well as the latest advancements in molecular targeted therapy. The aim of this study is to offer novel insights for clinical tumor therapy.

Head and neck squamous cell carcinoma (HNSCC) is a type of head and neck cancer that is aggressive, difficult to treat, and often associated with poor prognosis. HNSCC is the sixth most common cancer worldwide, highlighting the need to develop novel treatments for this disease. The current standard of care for HNSCC usually involves a combination of surgical resection, radiation therapy, and chemotherapy. Chemotherapy is notorious for its detrimental side effects including nausea, fatigue, hair loss, and more. Radiation therapy can be a challenge due to the anatomy of the head and neck area and presence of normal tissues. In addition to the drawbacks of chemotherapy and radiation therapy, high morbidity and mortality rates for HNSCC highlight the urgent need for alternative treatment options. Immunotherapy has recently emerged as a possible treatment option for cancers including HNSCC, in which monoclonal antibodies are used to help the immune system fight disease. Combining monoclonal antibodies approved by the US Food and Drug Administration, such as cetuximab and pembrolizumab, with radiotherapy or platinum-based chemotherapy for patients with locally advanced, recurrent, or metastatic HNSCC is an accepted first-line therapy. Targeted radionuclide therapy can potentially be used in conjunction with the first-line therapy, or as an additional treatment option, to improve patient outcomes and quality of life. Epidermal growth factor receptor is a known molecular target for HNSCC; however, other targets such as human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, programmed cell death protein 1, and programmed death-ligand 1 are emerging molecular targets for the diagnosis and treatment of HNSCC. To develop successful radiopharmaceuticals, it is imperative to first understand the molecular biology of the disease of interest. For cancer, this understanding often means detection and characterization of molecular targets, such as cell surface receptors, that can be used as sensitive targeting agents. The goal of this review article is to explore molecular targets for HNSCC and dissect previously conducted research in nuclear medicine and provide a possible path forward for the development of novel radiopharmaceuticals used in targeted radionuclide therapy for HNSCC, which has been underexplored to date.

Oral cancers, specifically oral squamous cell carcinoma (OSCC), pose a significant global health challenge, with high incidence and mortality rates. Conventional treatments such as surgery, radiotherapy, and chemotherapy have limited effectiveness and can result in adverse reactions. However, as an alternative, photodynamic therapy (PDT) has emerged as a promising option for treating oral cancers. PDT involves using photosensitizing agents in conjunction with specific light to target and destroy cancer cells selectively. The photosensitizers accumulate in the cancer cells and generate reactive oxygen species (ROS) upon exposure to the activating light, leading to cellular damage and ultimately cell death. PDT offers several advantages, including its non-invasive nature, absence of known long-term side effects when administered correctly, and cost-effectiveness. It can be employed as a primary treatment for early-stage oral cancers or in combination with other therapies for more advanced cases. Nonetheless, it is important to note that PDT is most effective for superficial or localized cancers and may not be suitable for larger or deeply infiltrating tumors. Light sensitivity and temporary side effects may occur but can be managed with appropriate care. Ongoing research endeavors aim to expand the applications of PDT and develop novel photosensitizers to further enhance its efficacy in oral cancer treatment. This review aims to evaluate the effectiveness of PDT in treating oral cancers by analyzing a combination of preclinical and clinical studies.

Oral cancer (OC) stands as a prominent cause of global mortality. Despite numerous efforts in recent decades, the efficacy of novel therapies to extend the lifespan of OC patients remains disappointingly low. Consequently, the demand for innovative therapeutic agents has become all the more pressing. In this context, we present our work on the design and synthesis of twenty-five novel quinoxaline-tethered imidazopyri(mi)dine derivatives. This was followed by comprehensive investigations into the impact of these molecules on the OC cell line. The in vitro cytotoxicity studies performed in CAL-27 and normal oral epithelial (NOE) cell lines revealed that some of the synthesized molecules like 12d have potent antiproliferative activity specifically towards OC cells with an IC50 of 0.79 μM and show negligible cytotoxicity over NOE cells. Further, 12d arrested cell growth in the S phase of the cell cycle and induced cell death by early apoptosis. The in silico studies validated that 12d binds to the activator binding site on pyruvate kinase M2 (PKM2) overexpressed in OC while the lactate dehydrogenase (LDH)-coupled enzyme assay established 12d as a potent PKM2 activator with an AC50 of 0.6 nM. Hence, this study provides fruitful evidence for the designed compounds as anticancer agents against OC.

Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control.

Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden.

From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: - 0.97%; 95% CI: - 1.89%, - 0.04%), and the similar trend was observed among females (AAPC: - 1.22%; 95% CI: - 1.89%, - 0.55%). The ASMR of males was 2.31-3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: - 1.31%, 95% CI: - 2.24% ~  - 0.37%) and for female (AAPC: - 1.63%, 95% CI: - 2.30% ~  - 0.95%). ASMR in urban areas was 1.02-1.28 times higher than that in rural areas from 2006 to2011, but 0.85-0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021.

There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.

To explore the expression of HAUS6 in squamous cell carcinoma of the tongue (TSCC) and its relationship with the clinicopathological features of patients, and to further provide new ideas and therapeutic targets for curing TSCC.

The Cancer Genome Atlas (TCGA) database was used to screen for differentially expressed genes (DEGs) between TSCC and normal tissues and survival analysis. DEGs of HAUS6 were screened and analyzed for GO, KEGG and GSEA enrichment. Exploring the correlation of HAUS6 with immune cell infiltration and immune checkpoint-related genes. The expression of HAUS6 in tumor and paraneoplastic tissues was confirmed by immunohistochemistry and Western Blot.

Analysis of the TCGA database results showed that expression of HAUS6 mRNA was significantly enhanced and correlated with overall survival (OS, p < 0.05) in TSCC. HAUS6 expression correlated with the level of immune cell infiltration and immune checkpoint-related genes. Immunohistochemistry and Western Blot confirmed that the expression level of HAUS6 protein was significantly higher in tumor tissues than in paraneoplastic tissues, and that tumor size and hypo-differentiation were higher in the HAUS6 high expression group than in the low expression group in TSCC (p < 0.05).

In conclusion, these analyses suggest that HAUS6 can act as an independent predictor of prognosis (p < 0.05) and high HAUS6 expression is strongly associated with poor prognosis.

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC.

Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential.

Live-dead cell staining and CCK-8 assays proved that Fe3O4 nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of Fe3O4 nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of Fe3O4 nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining.

The stable photothermal properties of Fe3O4 nanoparticles were validated by in vitro cellular and in vivo animal experiments. Fe3O4 photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival.

In this study, we applied Fe3O4 photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.

To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA).

Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence.

Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI.

The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen.

PROSPERO CRD42023460267.

Radiotherapy for head and neck tumors can lead to a severe complication known as radiation-induced brain injury (RIBI). However, the underlying mechanism of RIBI development remains unclear, and limited prevention and treatment options are available. Neuroactive steroids have shown potential in treating neurological disorders. 5α-Androst-3β, 5, 6β-triol (TRIOL), a synthetic neuroprotective steroid, holds promise as a treatment candidate for RIBI patients. However, the neuroprotective effects and underlying mechanism of TRIOL on RIBI treatment are yet to be elucidated. In the present study, our findings demonstrate TRIOL's potential as a neuroprotective agent against RIBI. In gamma knife irradiation mouse model, TRIOL treatment significantly reduced brain necrosis volume, microglial activation, and neuronal loss. RNA-sequencing, immunofluorescence, real-time quantitative polymerase chain reaction, siRNA transfection, and western blotting techniques revealed that TRIOL effectively decreased microglial activation, proinflammatory cytokine release, neuron loss, and guanylate-binding protein 5 (GBP5) expression, along with its downstream signaling pathways NF-κB and NLRP3 activation in vitro. In summary, TRIOL effectively alleviate RIBI by inhibiting the GBP5/NF-κB/NLRP3 signal axis, reducing microglia activation and pro-inflammation cytokines release, rescuing neuron loss. This study highlights the potential of TRIOL as a novel and promising therapy drug for RIBI treatment.

In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage.

Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced).

CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients.

TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.