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Nature Reviews. Disease Primers Nov 2020Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell... (Review)
Review
Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.
Topics: Human papillomavirus 16; Humans; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Tobacco Use
PubMed: 33243986
DOI: 10.1038/s41572-020-00224-3 -
Medical Sciences (Basel, Switzerland) Jun 2023Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands,... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11-12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations.
Topics: Male; Female; Humans; Adolescent; Child; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomavirus Infections; Risk Factors
PubMed: 37367741
DOI: 10.3390/medsci11020042 -
Annals of Oncology : Official Journal... Nov 2020
Topics: Carcinoma, Squamous Cell; Follow-Up Studies; Head and Neck Neoplasms; Humans; Hypopharynx; Larynx; Mouth; Oropharynx
PubMed: 33239190
DOI: 10.1016/j.annonc.2020.07.011 -
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 -
Head and Neck Pathology Mar 2022In this article, we review the chapter on tumors of the larynx, hypopharynx, trachea and parapharyngeal space in the new edition of the WHO book, focusing on the new... (Review)
Review
In this article, we review the chapter on tumors of the larynx, hypopharynx, trachea and parapharyngeal space in the new edition of the WHO book, focusing on the new developments in comparison to the previous edition. Squamous cell carcinoma (SCC) and its variants are by far the most common malignancies at these locations, with very limited new insights. The most important is the introduction of new targeted treatment-checkpoint inhibitors, with a new task for pathologists, who may help to predict the response to treatment by analyzing the expression of targeted proteins in biopsy samples. Precancerous lesions remain a controversial topic and, similarly to other organs, it is acceptable to use the terms "dysplasia" or "squamous intraepithelial lesion" (SIL), but there is a slight difference between low-grade dysplasia and low-grade SIL: in the former, mild atypia must be present, while the latter also includes hyperplastic epithelium without atypia. Two approaches have been proposed: a two-tiered system with low- and high-grade dysplasia/SIL and a three-tiered system with an additional category, carcinoma in situ. We are still searching for reliable diagnostic markers to surpass the subjectivity in biopsy diagnosis, with a few potential candidate markers on the horizon, e.g., stem cell markers. Other tumors are rare at these locations, e.g., hematolymphoid, neuroendocrine and salivary gland neoplasms, and are no longer included in Chapter 3. They must be diagnosed according to criteria described in specific chapters. The same holds true for soft tissue tumors, with the exception of cartilaginous neoplasms, which are still included in Chapter 3.
Topics: Carcinoma in Situ; Head and Neck Neoplasms; Humans; Hypopharynx; Larynx; Parapharyngeal Space; Trachea; World Health Organization
PubMed: 35312977
DOI: 10.1007/s12105-021-01405-6 -
JAMA Surgery Jul 2021Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE.
OBJECTIVE
To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial.
DESIGN, SETTING, AND PARTICIPANTS
This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020.
INTERVENTION
Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis.
MAIN OUTCOMES AND MEASURES
The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life.
RESULTS
Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer.
TRIAL REGISTRATION
Trialregister.nl Identifier: NL4183 (NTR4333).
Topics: Aged; Anastomosis, Surgical; Anastomotic Leak; Carcinoma; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Humans; Length of Stay; Male; Middle Aged; Minimally Invasive Surgical Procedures; Netherlands; Quality of Life; Treatment Outcome
PubMed: 33978698
DOI: 10.1001/jamasurg.2021.1555 -
Frontiers in Endocrinology 2023No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases.
BACKGROUND
No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases.
METHODS
BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method.
RESULTS
This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200).
CONCLUSION
This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Laryngitis; Mendelian Randomization Analysis; Lung Neoplasms; Respiratory Tract Infections; Bronchiectasis
PubMed: 37711902
DOI: 10.3389/fendo.2023.1197730 -
Ear, Nose, & Throat Journal May 2022To evaluate the characteristics of laryngopharyngeal reflux (LPR) in patients with different hypertrophic laryngeal diseases and to explore the relationship between LPR...
OBJECTIVES
To evaluate the characteristics of laryngopharyngeal reflux (LPR) in patients with different hypertrophic laryngeal diseases and to explore the relationship between LPR and these diseases.
METHODS
A retrospective analysis was performed. The clinical data of 154 patients were collected. According to their diagnoses, patients were divided into 3 groups. Group 1 included 49 patients with vocal cord polyps. Group 2 contained 52 patients with vocal cord leukoplakia. Group 3 included 53 patients with laryngeal carcinoma. The reflux symptom indexes (RSIs), reflux finding scores (RFSs), and Ryan scores of all patients were evaluated and compared.
RESULTS
Patients with vocal cord polyps were the youngest of the 3 groups, and those with laryngeal carcinoma were the oldest. A male preponderance emerged in each group. In total, 128 patients (83.12%) had positive RSI/RFS values and 60 (60/146, 41.1%) patients had positive Ryan scores. The positive RSI/RFS rates of both groups 1 and 2 (89.80% and 92.16%, respectively) were significantly higher than that of group 3 (69.81%). Moreover, the positive Ryan score rates in both groups 1 and 2 (39.58% and 53.85%, respectively) were significantly higher than that of group 3 (28.26%).
CONCLUSIONS
Laryngopharyngeal reflux occurs in many patients with vocal cord polyps, vocal cord leukoplakia, and vocal cord carcinoma, indicating that LPR may be important in the pathogenesis of these diseases. Laryngopharyngeal reflux occurs more common in patients with vocal cord polyps and leukoplakia and less common in those with laryngeal carcinoma, suggesting the role of LPR on these diseases may be different.
Topics: Carcinoma; Humans; Laryngeal Diseases; Laryngeal Neoplasms; Laryngopharyngeal Reflux; Leukoplakia; Male; Polyps; Retrospective Studies; Vocal Cords
PubMed: 32865459
DOI: 10.1177/0145561320953232 -
Journal of B.U.ON. : Official Journal... 2020During laryngeal carcinogenesis, a variety of genomic imbalances are involved in hyperplastic and dysplastic laryngeal epithelia as early or progressive genetic events,... (Review)
Review
During laryngeal carcinogenesis, a variety of genomic imbalances are involved in hyperplastic and dysplastic laryngeal epithelia as early or progressive genetic events, respectively. Oncogenes' overactivation is a crucial genetic event in malignant and pre-malignant neoplastic epithelia. Especially, deregulation of crucial pathways including transcription factors - such as c-Fos and c-Jun - leads to an aberrant expression of other crucial genes responsible for cell homeostasis. Upregulation of c-Fos and c-Jun proto-oncogenes -due to increased copy numbers (amplification) or intra-genic point mutations- seems to be correlated with aggressive biological behaviour in laryngeal squamous cell carcinomas (LSCCs). In the current special molecular article we explored the role of c-Fos/c-Jun complex deregulation in LSCC.
Topics: Animals; Genes, fos; Genes, jun; Humans; Laryngeal Neoplasms; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Signal Transduction; Squamous Cell Carcinoma of Head and Neck
PubMed: 32521843
DOI: No ID Found