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HNO Feb 2023Human papillomaviruses (HPV) 6 and 11 cause 90% of recurrent laryngeal papillomatosis (RLP). It is unclear whether recurrences are caused by new infections or the... (Review)
Review
Human papillomaviruses (HPV) 6 and 11 cause 90% of recurrent laryngeal papillomatosis (RLP). It is unclear whether recurrences are caused by new infections or the spread of infected cells. Symptomatic and sometimes curative treatment is laser surgery or conventional microsurgical removal. RLP surgery aims to relieve shortness of breath and improve the voice. Patients (especially children) are affected by voice problems, repetitive surgeries, pulmonary manifestations, and psychological trauma. Vaccination with Gardasil 9 (Merck & Co., Rahway, NJ, USA) prevents new infections with HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 and induces vaccine antigen-specific antibodies and CD4+ T helper cells. According to current studies, RLP can be avoided with prophylactic vaccination. The treatment is associated with a general vaccination risk (European Medicines Agency approval: girls and boys from 9 years). Studies also show that the vaccine after removal of HPV-associated neoplasia/papilloma prevents recurrences. Extension of the vaccination recommendation to prevent recurrences of HPV-associated diseases in men may promote applicability and herd immunity. For rare and treatment-refractory cases with laryngotracheal involvement, systemic therapy with bevacizumab (e.g. Avastin; Genentech, San Francisco, CA, USA), a VEGF antibody, is a promising adjuvant treatment option.
Topics: Male; Child; Female; Humans; Papillomavirus Infections; Laryngeal Neoplasms; Papilloma; Recurrence; Respiratory Tract Infections
PubMed: 36477391
DOI: 10.1007/s00106-022-01250-1 -
Journal of Experimental & Clinical... Feb 2021Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the...
BACKGROUND
Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood.
METHODS
The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability.
RESULTS
The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a "writer" of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent.
CONCLUSION
Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.
Topics: Animals; Apoptosis Regulatory Proteins; Cell Proliferation; Disease Progression; Heterografts; Humans; Laryngeal Neoplasms; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Protein Stability; RNA-Binding Proteins; Squamous Cell Carcinoma of Head and Neck
PubMed: 33637103
DOI: 10.1186/s13046-021-01871-4 -
JAMA Network Open Nov 2020Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for...
IMPORTANCE
Postoperative chemoradiation is the standard of care for cancers with positive margins or extracapsular extension, but the benefit of chemotherapy is unclear for patients with other intermediate risk features.
OBJECTIVE
To evaluate whether machine learning models could identify patients with intermediate-risk head and neck squamous cell carcinoma who would benefit from chemoradiation.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx from January 1, 2004, through December 31, 2016. Patients had resected disease and underwent adjuvant radiotherapy. Analysis was performed from October 1, 2019, through September 1, 2020. Patients were selected from the National Cancer Database, a hospital-based registry that captures data from more than 70% of newly diagnosed cancers in the United States. Three machine learning survival models were trained using 80% of the cohort, with the remaining 20% used to assess model performance.
EXPOSURES
Receipt of adjuvant chemoradiation or radiation alone.
MAIN OUTCOMES AND MEASURES
Patients who received treatment recommended by machine learning models were compared with those who did not. Overall survival for treatment according to model recommendations was the primary outcome. Secondary outcomes included frequency of recommendation for chemotherapy and chemotherapy benefit in patients recommended for chemoradiation vs radiation alone.
RESULTS
A total of 33 527 patients (24 189 [72%] men; 28 036 [84%] aged ≤70 years) met the inclusion criteria. Median follow-up in the validation data set was 43.2 (interquartile range, 19.8-65.5) months. DeepSurv, neural multitask logistic regression, and survival forest models recommended chemoradiation for 17 589 (52%), 15 917 (47%), and 14 912 patients (44%), respectively. Treatment according to model recommendations was associated with a survival benefit, with a hazard ratio of 0.79 (95% CI, 0.72-0.85; P < .001) for DeepSurv, 0.83 (95% CI, 0.77-0.90; P < .001) for neural multitask logistic regression, and 0.90 (95% CI, 0.83-0.98; P = .01) for random survival forest models. No survival benefit for chemotherapy was seen for patients recommended to receive radiotherapy alone.
CONCLUSIONS AND RELEVANCE
These findings suggest that machine learning models may identify patients with intermediate risk who could benefit from chemoradiation. These models predicted that approximately half of such patients have no added benefit from chemotherapy.
Topics: Aged; Chemoradiotherapy, Adjuvant; Cohort Studies; Deep Learning; Female; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Logistic Models; Lymph Nodes; Machine Learning; Male; Mouth Neoplasms; Neoplasm Grading; Neoplasm Staging; Neural Networks, Computer; Oropharyngeal Neoplasms; Otorhinolaryngologic Surgical Procedures; Patient Selection; Proportional Hazards Models; Radiotherapy, Adjuvant; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tumor Burden
PubMed: 33211108
DOI: 10.1001/jamanetworkopen.2020.25881 -
International Journal of Cancer Nov 2020Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now,...
Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now, reducing the high mortality remains difficult. Understanding the cellular heterogeneity of LSCC could contribute to improve this problem. Single-cell RNA sequencing was applied to dissect the cell composition and molecular characteristics of LSCC tissues. Immunohistochemistry staining of the LSCC tissues was performed to identify the spatial location of tumor cells. Survival analysis of marker genes was executed in The Cancer Genome Atlas to verify the correlation between each cell clusters and patients' prognosis. The LSCC tissue cells were finely grouped into various clusters, including tumor cells, immune cells, epithelial cells, fibroblasts and endothelial cells. Notably, in tumor cells, keratinocyte-like cells were in the core of tumor while malignant proliferating cells were located at the tumor edge. The malignant proliferating cells were correlated with poor prognosis. In summary, this is the first study to delineate a landscape of the LSCC intratumor heterogeneity. Our work might help researchers have a better understanding for tumor progression.
Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Laryngeal Neoplasms; Male; Middle Aged; Prognosis; Sequence Analysis, RNA; Single-Cell Analysis; Survival Analysis
PubMed: 32638385
DOI: 10.1002/ijc.33192 -
European Annals of Otorhinolaryngology,... Dec 2021
Topics: Humans; Laryngeal Neoplasms
PubMed: 34083172
DOI: 10.1016/j.anorl.2021.05.006 -
European Annals of Otorhinolaryngology,... May 2021
Topics: Chondroma; Humans; Laryngeal Neoplasms; Larynx
PubMed: 32811795
DOI: 10.1016/j.anorl.2020.08.003 -
Advances in Therapy Jul 2019A new edition of the World Health Organization (WHO) Histological classification of tumours of the hypopharynx, larynx, trachea and parapharyngeal space was published in... (Review)
Review
A new edition of the World Health Organization (WHO) Histological classification of tumours of the hypopharynx, larynx, trachea and parapharyngeal space was published in 2017. We have considered this classification regarding laryngeal neoplasms and discuss the grounds for said revision. Many of the laryngeal neoplasms described in the literature and in the previous WHO edition from 2005 have been omitted from this current revision. Many are described elsewhere in the book but it may give the new generation of pathologists/surgeons/oncologists the false impression that these tumour entities do not exist in the larynx.
Topics: Classification; Humans; Immunohistochemistry; Laryngeal Neoplasms; World Health Organization
PubMed: 31119694
DOI: 10.1007/s12325-019-00978-7 -
Advances in Therapy Jan 2020Paraneoplastic syndromes occur rarely in association with laryngeal cancer. When present, the syndrome may be the first sign of the malignancy. The aim of the present... (Review)
Review
OBJECTIVES
Paraneoplastic syndromes occur rarely in association with laryngeal cancer. When present, the syndrome may be the first sign of the malignancy. The aim of the present study was to review and report on all published cases in the international literature.
METHODS
A search of PubMed was conducted for "paraneoplastic syndromes in laryngeal cancer" without any restrictions on language or publication year. The full texts of all relevant articles were reviewed and all cases of paraneoplastic syndromes associated with any type of laryngeal cancer were extracted and analyzed.
RESULTS
We identified 59 cases of paraneoplastic syndromes related to laryngeal cancer in the literature published from 1963 until recently. There were 46 squamous cell carcinomas and 10 neuroendocrine carcinomas. Twenty-two of the paraneoplastic syndromes involved the endocrine system, 21 were dermatologic or cutaneous, 8 neurologic, 5 osteoarticular or rheumatologic, 1 ocular, 1 muscular, and 1 hematologic. Treatment strategies included surgery, radiotherapy, chemotherapy, and often multimodal therapy, depending on the histology and stage of the laryngeal cancer.
CONCLUSIONS
Because of their rarity, paraneoplastic syndromes associated with laryngeal cancer are difficult to diagnose. By presenting and systematically reviewing all published cases in the international literature, the present review may help clinicians to recognize them and to suspect the diagnosis of laryngeal cancer at an earlier stage than otherwise might be possible.
Topics: Humans; Laryngeal Neoplasms; Male; Paraneoplastic Syndromes
PubMed: 31802393
DOI: 10.1007/s12325-019-01160-9 -
European Archives of... Mar 2022Carcinosarcoma, also known as Spindle Cell Carcinoma (SpCC), is a rare type of malignant tumor. Generally, this type of pathology occurs in the urogenital tract, the... (Review)
Review
PURPOSE
Carcinosarcoma, also known as Spindle Cell Carcinoma (SpCC), is a rare type of malignant tumor. Generally, this type of pathology occurs in the urogenital tract, the gastrointestinal tract, respiratory tract and mammary gland; in the larynx, SpCC represents only 2-3% of all malignancies. Due to its rarity, there is currently no generally acceptable treatment guideline for this disease. The aim of this study was to systematically review the literature of SpCC of larynx and report epidemiologic, clinicopathologic and main therapeutic approaches for this entity.
METHODS
A systematic literature review was performed using MEDLINE, EMBASE, PubMed and Scopus databases. For this review, the results were extrapolated in the period between January 1990 to September 2020. Data extraction was performed using a standard registry database. The clinical and pathological staging were recalculated according to the Eight Edition of AJCC Cancer Staging Manual and statistical analyses were performed using SPSS Version 25.0.
RESULTS
A total of 111 patients affected by laryngeal carcinosarcoma were included. From our review arises that surgery is the main treatment for primary laryngeal carcinosarcoma. In this way, various techniques such as minimally invasive laryngoscopy excision, laser CO2 cordectomy, partial laryngectomy (vertical and horizontal) and total laryngectomy. The role of radiotherapy is still controversial. The overall survival (OS) for T1 stage tumor at 5 years of follow-up is 82.9%, the OS for T2 and T3 tumor is 74% and 73.4%. The OS at 5 years of follow-up is 91.7% for supraglottic tumor, 69.3% for glottic tumor and 50% for transglottic site. Subglottic site is described in only 2 cases [12-13], so the OS at 5 years is not statistically significant. The 5-year overall survival in patients without lymph nodes involvement (N0) is 90.2%, 66.7% and 50%, respectively, for N1 and N2 lesions.
CONCLUSION
Primary laryngeal carcinosarcoma is a very rare malignancy. There are no clear guidelines in the management but in the literature, surgery is described as the best modality of therapy; radiation only can be a reasonable alternative with controversial efficacy. The most important prognostic factor is the nodal metastasis.
Topics: Carcinosarcoma; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Larynx; Neoplasm Staging; Retrospective Studies
PubMed: 34351467
DOI: 10.1007/s00405-021-07027-6 -
Ear, Nose, & Throat Journal Sep 2021Hoarseness lasting greater than 2 weeks should be thoroughly evaluated. Here, a case is presented of a 38-year-old female with a 10-year history of dysphonia. Endoscopic...
Hoarseness lasting greater than 2 weeks should be thoroughly evaluated. Here, a case is presented of a 38-year-old female with a 10-year history of dysphonia. Endoscopic examination confirmed the presence of a supraglottic mass, for which operative biopsy and imaging were performed. Pathology confirmed the diagnosis of supraglottic schwannoma. This was excised endoscopically with close management postoperatively to monitor for rapid recurrence and airway compromise. At one month postoperatively, the patient is still mildly dysphonic but vocally improved and the operative site continues to heal well.
Topics: Adult; Dysphonia; Epiglottis; Female; Hoarseness; Humans; Laryngeal Neoplasms; Laryngoscopy; Neurilemmoma
PubMed: 34112006
DOI: 10.1177/01455613211018586