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BACKGROUND: The efficacy of transoral robotic surgery (TORS) for HPV-negative oropharyngeal cancers (OPSCC) is less explored, especially regarding long-term outcomes and prognostic factors. METHODS: We conducted a retrospective monocentric study on 37 patients with HPV-negative OPSCC treated with TORS with a median follow-up of 3 years, assessing survival outcomes using Kaplan-Meyer statistics and swallowing function via the functional outcome swallowing scale (FOSS). Histopathological parameters were collected either from medical records or histology slides were re-evaluated. RESULTS: Patients demonstrated high disease-specific survival (DSS) but lower overall survival (OS), with a cohort characterized by high comorbidity rates. Vascular invasion was a significant adverse factor for relapse-free survival (RFS) and OS, while lymphatic invasion was not. Most patients demonstrated significant preservation of swallowing function. CONCLUSIONS: TORS for HPV-negative OPSCC demonstrates high DSS and preserved swallowing function. Vascular invasion is a key prognostic factor for survival outcomes.
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development.
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite advances in therapeutic management and immunotherapy, the five-year survival rate for head and neck cancer remains at ~66% of all diagnosed cases. A better definition of drivers of HPV-negative HNSCC that are targetable points of tumor vulnerability could lead to significant clinical advances. NSD1 is a histone methyltransferase which catalyzes histone H3 lysine 36 di-methylation (H3K36me2); mutations inactivating NSD1 have been linked to improved outcomes in HNSCC. In this study, we show that NSD1 induces H3K36me2 levels in HNSCC, and that the depletion of NSD1 reduces HNSCC of cell growth in vitro and in vivo. We also find that NSD1 strongly promotes activation of the Akt/mTORC1 signaling pathway. NSD1 depletion in HNSCC induces an autophagic gene program activation, causes accumulation of the p62 and LC3B-II proteins, and decreases the autophagic signaling protein ULK1 at both protein and mRNA levels. Reflecting these signaling defects, knockdown of NSD1 disrupts autophagic flux in HNSCC cells. Taken together, these data identify positive regulation of Akt/mTORC1 signaling and autophagy as novel NSD1 functions in HNSCC, suggesting that NSD1 may be of value as a therapeutic target in this cancer.
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OBJECTIVE: Management of head and neck cancer patients provides unique challenges. Palliation serves to optimise quality-of-life by alleviating suffering and maintaining dignity. Prompt recognition and management of suffering is paramount to achieving this. This study aimed to assess perceived confidence, knowledge and adequacy of palliative training among UK-based otolaryngologists. METHOD: Eight multiple-choice questions developed by five palliative care consultants via the Delphi method were distributed over five weeks. Knowledge, perceived confidence and palliative exposure among middle-grade and consultant otolaryngologists were assessed, alongside training deficits. RESULTS: Overall, 145 responses were collated from middle-grade (n = 88, 60.7 per cent) and consultant (n = 57, 39.3 per cent) otolaryngologists. The mean knowledge score was 5 out of 10, with 22.1 per cent (n = 32) stating confidence in palliative management. The overwhelming majority (n = 129, 88.9 per cent) advocated further training. CONCLUSION: A broad understanding of palliative care, alongside appropriate specialist involvement, is key in meeting the clinical needs of palliative patients. Curriculum integration of educational modalities such as simulation and online training may optimise palliative care.
Subject(s)
Head and Neck Neoplasms , Otolaryngology , Surgeons , Decision Making , Head and Neck Neoplasms/surgery , Humans , Palliative Care/methods , United KingdomABSTRACT
(1) Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies globally. An early diagnosis of this disease is crucial, and the detection of gene mutations in circulating tumour DNA (ctDNA) through a liquid biopsy is a promising non-invasive diagnostic method. This review aims to provide an overview of ctDNA mutations in HNSCC patients and discuss the potential use of this tool in diagnosis and prognosis. (2) Methods: A systematic search for articles published in the English language between January 2000 and April 2021 in the Medline and Scopus databases was conducted. (3) Results: A total of 10 studies published in nine publications were selected and analysed. Altogether, 390 samples were obtained from HNSCC patients, and 79 control samples were evaluated. The most often explored gene mutation in ctDNA was TP53. (4) Conclusions: The examination of a larger group of gene mutations and the use of a combination of multiple detection methods contribute to a higher detection rate of mutated ctDNA. More studies are necessary to verify these conclusions and to translate them into clinical practice.
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OBJECTIVE: Head and neck cancer survivors have increased risk of developing second primary tumors compared to overall population. Because second primary represents a major cause of morbidity and mortality in this population, early detection is fundamental. MATERIALS AND METHODS: In this 10-year single-institution study, we investigated the following: incidence, clinical-pathological risk factors, and survival of patients with second primary tumor. We included all patients with diagnosis of squamous cell carcinoma of the head and neck seen at the Modena University Hospital from 2008 to 2018. RESULTS: Among 1,177 patients included, 222 (18.9%) developed second primary tumor; its survival probability at 5 years was 40.6%. Alcohol consumption (p = .0055) and index cancer in oropharynx (p = .0029), supraglottic larynx (p = .0000), glottic larynx (p = .0222) were associated with higher risk of second primary. The most common second primary sites were head and neck district and lung (70, 31.5%, and 67, 30.2%, respectively). Head and neck district were more common in oral cavity (18, 43%) and oropharynx index cancer (20, 31%); lung second primary in hypopharynx (4, 40%), supraglottic larynx (17, 43%), and glottic larynx index cancer (23, 35%). CONCLUSION: Head and neck cancer survivors developing a second primary tumor have dismal prognosis. Tailored surveillance is recommended.