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Nature Communications Jul 2021Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic...
Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.
Topics: Animals; Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Epstein-Barr Virus Infections; Female; Gene Expression Regulation, Viral; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Methionine Adenosyltransferase; Mice; NF-kappa B; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Receptor, Transforming Growth Factor-beta Type II; Sequence Deletion; Signal Transduction; Tumor Escape; Whole Genome Sequencing; Xenograft Model Antitumor Assays
PubMed: 34234122
DOI: 10.1038/s41467-021-24348-6 -
European Archives of... Oct 2023The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the...
BACKGROUND
The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the preliminary outcomes of a potential new treatment protocol based on neoadjuvant chemotherapy (NCT) and transoral robotic surgery (TORS).
METHODS
A retrospective single-center case series was performed including a total of 20 patients diagnosed with a SCC of the PPW between October 2010 and September 2021. All patients successfully completed TORS with neck dissection after NCT. Adjuvant treatment was performed in the presence of adverse pathologic features. Loco-regional control (LRC), overall survival (OS), and disease-specific survival (DSS) were defined as the time from surgery to tumor recurrence or death, as appropriate. Survival estimates were calculated by Kaplan-Meier analysis. Surgical data and post-operative functional outcomes were also reported.
RESULTS
Estimated 3-year LRC, OS, and DSS rates (95% Confidence interval) were 59.7% (39.7-89.6), 58.6% (38.7-88.8), and 69.4% (49.9-96.6). The median hospital stay was 21 days (IQR 17.0-23.5). Oral diet and decannulation were achieved after a median of 14 days (IQR 12.0-15.0). Feeding tube and tracheostomy dependence after 6 months was observed in 3 (15%) and 2 (10%) patients, respectively.
CONCLUSIONS
The use of NCT followed by TORS for PPW SCC treatment appears to have good oncological and functional outcomes for both early and locally advanced cancers. Further randomized trials and site-specific guidelines are needed.
Topics: Humans; Retrospective Studies; Neoadjuvant Therapy; Robotic Surgical Procedures; Neoplasm Recurrence, Local; Pharyngeal Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Treatment Outcome
PubMed: 37395758
DOI: 10.1007/s00405-023-08070-1 -
Anti-cancer Drugs Feb 2023The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head...
The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head and neck SPTs. We describe the cases of eight patients, each with an SPT of the oropharynx. These developed after a long median latency of 17.7 years with each receiving two-dimensional radiation therapy and delivery of at least 5000 cGy per pharynx, except for one who was treated with IMRT. Tumor histological commonalities revealed squamous cell carcinoma p16 negative staining, local invasion, and limited lymphatic spread, with posterior wall of the oropharynx and the base of the tongue being the most common locations. Limited and challenging treatment options have been reported such as surgery, reirradiation, or clinical trials. Radiation-induced SP oropharyngeal carcinoma has unique clinical and pathological features. Patients with this disease have limited treatment options, which should be discussed in a multidisciplinary tumor board meeting. For this population, lifelong follow-up may help in early diagnosis and improve outcomes.
Topics: Humans; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Oropharynx; Retrospective Studies
PubMed: 36730617
DOI: 10.1097/CAD.0000000000001411 -
Journal of the American Society of... 2020Human papillomavirus (HPV)-related oropharyngeal carcinoma can morphologically mimic many processes from benign to malignant and lead pathologists to incorrectly... (Review)
Review
Human papillomavirus (HPV)-related oropharyngeal carcinoma can morphologically mimic many processes from benign to malignant and lead pathologists to incorrectly diagnose them and/or use inappropriate diagnostic terminology. Recognition of HPV-related oropharyngeal carcinoma and its variants is critical for appropriate prognostic and therapeutic considerations in small biopsy material. Various pitfalls in diagnosing these tumors on limited biopsies are discussed herein.
Topics: Adult; Biomarkers, Tumor; Biopsy, Needle; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Human papillomavirus 16; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Oropharyngeal Neoplasms; Oropharynx; Papillomavirus Infections; Polymerase Chain Reaction; Squamous Cell Carcinoma of Head and Neck
PubMed: 32651129
DOI: 10.1016/j.jasc.2020.06.001 -
European Review For Medical and... Apr 2023Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the...
OBJECTIVE
Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the cellular level of the mucosa and squamous cell carcinoma (SCC).
PATIENTS AND METHODS
A total of 60 CLE sequences recorded in 5 patients with SCC undergoing laryngectomy between October 2020 and February 2021 were analyzed. The corresponding histologic sample derived from H&E staining was assigned to each sequence, capturing CLE images of the tumor and healthy mucosa. In addition, the cellular structure analysis was performed to diagnose SCC by measuring the total number of cells and cell size in 60 sequences in a fixed field of view (FOV) with 240 μm in diameter (45,239 μm2).
RESULTS
Out of 3,600 images, 1,620 (45%) showed benign mucosa and 1,980 (55%) SCC. The automated analysis yielded a difference in cell size, with healthy epithelial cells being 171.9±82.0 μm2 smaller than SCC cells, which were 246.3±171.9 μm2 and showed greater variability in size (p=0.037). In addition, due to the probe's fixed FOV, there was a difference in cell count with a total of 188.7±38.3 and 124.8±38.6 cells in images of normal epithelium and SCC (p<0.001), respectively. Regarding cell density as a criterion for the differentiation of benign/malign, using a cut-off value of 145.5 cells/FOV, we obtained sensitivity and specificity of 88.0% and 71.9%, respectively.
CONCLUSIONS
SCC reveals marked differences at a cellular level compared to the healthy epithelium. Our results further support the importance of this feature for identifying SCC during CLE imaging.
Topics: Humans; Microscopy, Confocal; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cell Count; Lasers
PubMed: 37140313
DOI: 10.26355/eurrev_202304_32146 -
Genes Jan 2024This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian...
This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Instrumental variables within ±100 kb of the gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95% 0.81~0.99, = 2.25 × 10; 95% 0.65~0.94, = 2.55 × 10). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95% 1.14~1.75, = 1.88 × 10; 95% 1.46~2.53, = 1.16 × 10; 95% 4.49~6.33, = 3.36 × 10; 95% 4.56~7.12, = 6.91 × 10), without heterogeneity or pleiotropy ( > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus ( > 0.05). Reverse MR helped mitigate reverse causation effects. The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.
Topics: Female; Humans; Proprotein Convertase 9; PCSK9 Inhibitors; Subtilisin; Mendelian Randomization Analysis; Proprotein Convertases; Breast Neoplasms; Lung Neoplasms; Pharyngeal Neoplasms; Carcinoma in Situ
PubMed: 38275613
DOI: 10.3390/genes15010132 -
Oral Oncology Jul 2020Transoral approaches for laryngeal/pharyngeal malignancies have been widely accepted as minimally invasive treatment options; however, hypopharyngeal lesions treated by...
OBJECTIVES
Transoral approaches for laryngeal/pharyngeal malignancies have been widely accepted as minimally invasive treatment options; however, hypopharyngeal lesions treated by transoral surgery have rarely been reported due to the difficulties in visualizing the hypopharynx. Since 2010, we have treated superficial hypopharyngeal lesions with endoscopic laryngopharyngeal surgery (ELPS), and herein report the outcomes of this transoral procedure.
MATERIALS AND METHODS
One hundred and eighteen patients with superficial hypopharyngeal lesions were treated by ELPS from February 2010 to February 2017, and the clinical courses of the patients were reviewed.
RESULTS
Four females and 114 males (average: 65.6 y-o) were included in this study. Some patients had multiple lesions and a total of 154 superficial hypopharyngeal lesions (dysplasia: 29, Tis: 52, T1: 44, T2: 20, T3: 9) were treated with ELPS. Ten patients had only dysplasia and no carcinoma. Five patients presented with nodal metastases and 11 patients had simultaneous oropharyngeal lesions. In all cases, the hypopharynx was well visualized with sufficient working space, and no cases required a change in surgical approach. All post-operative complications were safely managed. In regard to the oncological outcomes, of the 108 patients with malignant lesions, the 3-year and 5-year overall survival (OS) rate was 93.6% and 85.5%, respectively.
CONCLUSIONS
During ELPS, the hypopharynx was well visualized providing sufficient working space for the resection. The procedure was safe and feasible for superficial hypopharyngeal lesions and exhibited very good oncological outcomes. ELPS is thought to be a very effective surgical alternative for superficial hypopharyngeal lesions.
Topics: Adult; Aged; Aged, 80 and over; Endoscopy; Female; Humans; Hypopharynx; Laryngoscopy; Male; Middle Aged; Pharyngeal Neoplasms; Pharynx
PubMed: 32325303
DOI: 10.1016/j.oraloncology.2020.104655 -
Head & Neck Oct 2021Transoral robotic surgery (TORS) is an established treatment for many subsites of Head and Neck cancer. With the improved flexibility and access of the single-port (SP)...
Transoral robotic surgery (TORS) is an established treatment for many subsites of Head and Neck cancer. With the improved flexibility and access of the single-port (SP) robotic system, tumors within the distal upper aerodigestive tract can now be reached and successfully treated with all the published advantages of transoral endoscopic surgery. Here in we offer the first published surgical technique for SP TORS for resectable hypopharyngeal carcinoma. The video presented demonstrates many important aspects utilizing the enhanced robotic system, including adjustments of the semi-flexible endoscope and use of the third transoral surgical instrumentation. As previously reported, TORS hypopharyngectomy should be considered for resectable tumors to improve upon the deleterious effects of open surgical resection or chemoradiation therapy.
Topics: Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Robotic Surgical Procedures
PubMed: 34156733
DOI: 10.1002/hed.26794 -
Acta Oto-laryngologica Jan 2023The development of more sensitive biomarkers for the detection of early-stage head and neck squamous cell carcinoma is needed.
BACKGROUND
The development of more sensitive biomarkers for the detection of early-stage head and neck squamous cell carcinoma is needed.
AIMS/OBJECTIVES
This study was performed to assess the value of serum p53 antibody (s-p53-Ab) as a biomarker for oral and pharyngeal carcinoma.
MATERIAL AND METHODS
Pre-treatment serum was collected for 71 patients with oral and pharyngeal carcinoma and 117 healthy volunteers as controls and analyzed s-p53-Ab using enzyme-linked immunosorbent assay (ELISA).
RESULTS
Using 1.3 U/mL as the cut-off value, 14 of 71 patients (sensitivity 19.7%), and 12 of 117 control cases were positive for s-p53-Ab (specificity 89.7%). Excluding 12 cases of p16-positive oropharyngeal and nasopharyngeal cancer which were all negative for s-p53-Ab, the sensitivity in early-stage 1-2 cases was 30.0%, which was higher than conventional tumor markers.
CONCLUSIONS AND SIGNIFICANCE
The s-p53-Ab was not detected in any cases of virus-related cancer in which p53 gene mutations were not involved in carcinogenesis. Since the s-p53-Ab sensitivity was high even in early-stage disease, s-p53-Ab measurement may be useful as an early diagnostic biomarker in patients with oral, p16- oropharyngeal, and hypopharyngeal cancer.
Topics: Humans; Antibodies; Biomarkers, Tumor; Pharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tumor Suppressor Protein p53
PubMed: 36694958
DOI: 10.1080/00016489.2023.2165144 -
ORL; Journal For Oto-rhino-laryngology... 2020The rise in primary surgical management of oropharyngeal squamous cell carcinoma has led to varying interpretations of the histopathologic evaluation following a radical...
INTRODUCTION
The rise in primary surgical management of oropharyngeal squamous cell carcinoma has led to varying interpretations of the histopathologic evaluation following a radical tonsillectomy. The oncologic margin may be significantly influenced by the morphologic relations and anatomic dimensions of the palatine tonsil and superior pharyngeal constrictor (SPC) muscle.
OBJECTIVE
The aim of this study was to characterize the gross and histologic anatomic features of the palatine tonsil and SPC muscle following an en bloc radical tonsillectomy.
METHODS
Radical tonsillectomy specimens were collected from cadaveric and oncologic subjects. Specimens were processed using standard histopathologic techniques and were analyzed by a board-certified head and neck pathologist. The thickness of the SPC muscle and relationship to the tonsillar carcinoma were assessed.
RESULTS
Six cadaveric and 10 oncologic specimens were analyzed. The mean minimum SPC width for all cadaveric specimens was 1.02 ± 0.50 mm. The mean minimum width for oncologic specimens was 0.76 ± 0.46 mm. The mean distance from tonsil carcinoma to the lateral specimen margin was 1.79 ± 1.39 mm.
CONCLUSION
Due to the limited width of the SPC muscle, a margin in excess of 2 mm may not be attainable in a transoral radical tonsillectomy. Margin status may be ideally determined by the integrity of the SPC muscle in future oncologic studies, rather than an adequate distance measurement.
Topics: Cadaver; Carcinoma, Squamous Cell; Humans; Palatine Tonsil; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck; Tonsillar Neoplasms; Tonsillectomy
PubMed: 32659762
DOI: 10.1159/000508136