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.

OBJECTIVE: The main objective of this study is to analyze factors associated with nodal yield in level II-IV selective neck dissections (NDs) and the secondary objective is to assess its impact on overall and disease-free survival.
METHODS: Observational retrospective study including adult patients submitted to level II-IV ND from January 2015 to December 2021 in the otorhinolaryngology department of a tertiary hospital center.
RESULTS: A total of 44 patients and 78 level II-IV NDs (34 bilateral and 10 unilateral) were included. The median age at diagnosis was 60 (22-74) years, and 93.2% of the patients were male. A lower nodal yield was significantly associated with previous radiotherapy (p = 0.042) and extranodal invasion (p < 0.001) and was non-significantly associated with older age (p = 0.065). Furthermore, on a Cox analysis adjusted to the cN status and age, the nodal yield was not associated with five-year disease-free survival (HR = 0.986; 95% CI = 0.922-1.054; p = 0.681) nor with five-year overall survival (HR = 1.006; 95% CI = 0.925-1.095; p = 0.888).
CONCLUSIONS: A reduced nodal yield in level II-IV NDs was significantly associated with previous radiotherapy and extranodal extension and non-significantly associated with age. There was no association between the nodal yield and five-year overall survival or disease-free survival.

OBJECTIVE: This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC).
METHODS: Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS).
RESULTS: A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older.
CONCLUSIONS: This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment.

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance.

In the vast landscape of human health, head and neck cancer (HNC) poses a significant health burden globally, necessitating the exploration of novel diagnostics and therapeutics. Metabolic alterations occurring within tumor microenvironment are crucial to understand the foundational cause of HNC. Post-translational modifications (PTMs) have recently emerged as a silent foe exerting a significantly heightened influence on various aspects of the biological processes associated with the onset and advancement of cancer, particularly in the context of HNC. There are numerous targets involved in HNC but recently, the enzyme pyruvate kinase M2 (PKM2) has come out as a hot target due to its involvement in glycolysis resulting in metabolic reprogramming of cancer cells. Various PTMs have been reported to affect the structure and function of PKM2 by modulating its activity. This review aims to investigate the impact of PTMs on the interaction between PKM2 and several signaling pathways and transcription factors in the context of HNC. These interactions possess significant ramification for cellular proliferation, apoptosis, angiogenesis and metastasis. This review primarily explores the role of PTMs influencing PKM2 and its involvement in tumor development. While acknowledging the significance of PKM2 interactions with other tumor regulators, the emphasis lies on dissecting PTM-related mechanisms rather than solely scrutinizing individual regulators. It lays the framework for the development of more sophisticated diagnostic tools and uncovers exciting possibilities for precision medicine essential for effectively addressing the complexity of this malignancy in a precise and focused manner.

Introduction Head and neck squamous cell carcinoma (HNSCC) is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habits like tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effects like difficulty swallowing, leading to complications such as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients\' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOG scale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOG criteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

The Human Papillomavirus (HPV) is a sexually transmitted infection that significantly affects the population worldwide. HPV preventive methods include vaccination, prophylactics, and education. Different types of cancers associated with HPV usually take years or decades to develop after infections, such as Head and Neck Cancer(HNC). Therefore, HPV prevention can be considered cancer prevention. A sample of medical students in Puerto Rico was evaluated to assess their knowledge about HPV, HPV vaccine, and HNC through two previously validated online questionnaires composed of 38 dichotomized questions, we measured HPV, HPV vaccination(HPVK), and HNC knowledge (HNCK). Out of 104 students surveyed, the mean HPVK score obtained was 20.07/26, SD = 3.86, while the mean score for HNCK was 6.37/12, SD = 1.78. Bidirectional stepwise regression showed study year and HPV Vaccine name had been the most influential variables on HPVK and HNCK. MS1 participants scored lower than MS2-MS4 participants, with no significant difference between MS2-MS4 scores. The results reveal knowledge gaps in HPV/HPV Vaccine and HNC among surveyed medical students. Our findings also suggest an association between knowledge of personal vaccination status, self-perceived risk, and how uncertainty in these factors may affect the medical students\' understanding of HPV, HPV vaccination, and associated cancers.

OBJECTIVE: Head and neck cancers (HNCs) encompass a complex group of malignancies with high morbidity, often leading to critical emergencies such as pain crises, airway obstruction and hemorrhage. This review aims to outline an evidence-based approach to the multidisciplinary management of HNC oncologic emergencies with a focus on the role of emergent radiotherapy (RT).
METHODS: A literature search was performed using Medline, Embase and the Cochrane Central Register of Controlled Trials databases with a focus on three common oncological emergencies using the following keywords: \"head and neck cancer\", \"radiation OR radiotherapy\", \"pain\", \"bleeding OR haemorrhage\", and \"airway obstruction\". All English language articles published up to April 2022 were screened to identify studies pertaining to the management of oncologic emergencies in HNC.
UNASSIGNED: The management of oncologic emergencies in HNC present a unique set of challenges that require early recognition and aggressive treatment. In this narrative review, we summarize the evidence supporting the role of RT in the management of HNC patients presenting with pain crisis, malignant airway obstruction and acute haemorrhage. We demonstrate that while RT can be used as a primary or adjunct therapy, optimal management depends on the involvement of a multi-disciplinary team that includes head and neck surgeons, interventional radiology and palliative care.
CONCLUSIONS: RT plays a critical role in the multidisciplinary management of HNC oncological emergencies. Further prospective and comparative studies are needed to assess optimal management strategies.

BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity.
METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS).
RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively.
CONCLUSIONS: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Head and neck cancer (HNC) is the 6th most common cancer across the world, with a particular increase in HNC associated with human papilloma virus (HPV) among younger populations. Historically, the standard treatment for this disease consisted of combined surgery and radiotherapy or curative platinum-based concurrent chemoradiotherapy, with associated long term and late toxicities. However, HPV-positive HNC is recognized as a unique cancer subtype, typically with improved clinical outcomes. As such, treatment de-escalation strategies have been widely researched to mitigate the adverse effects associated with the current standard of care without compromising efficacy. These strategies include treatment de-escalation, such as novel surgical techniques, alternative radiation technologies, radiation dose and volume reduction, as well as neoadjuvant chemotherapies, immunotherapies, and combined therapies. Although these therapies show great promise, many of them are still under investigation due to hesitation surrounding their widespread implementation. The objective of this review is to summarize the most recent progress in de-escalation strategies and neoadjuvant therapies designed for HPV-positive HNC. While specific treatments may require additional research before being widely adopted, encouraging results from recent studies have highlighted the advantages of neoadjuvant chemotherapy and immunotherapy, as well as radiation and surgical de-escalation approaches in managing HPV-positive HNC.