ABSTRACT
OBJECTIVES: To report a single institution's experience using human papillomavirus (HPV) E6/E7 mRNA in-situ hybridization (mRNA ISH) for HPV detection in oropharyngeal squamous cell carcinoma (OPSCC). To review the literature on HPV detection methods. STUDY DESIGN: Retrospective chart review, literature review. SETTING: Tertiary care academic hospital. SUBJECTS AND METHODS: We conducted a retrospective chart review of 122 OPSCC biopsy specimens. mRNA ISH was performed on formalin-fixed paraffin-embedded (FFPE) tissue with a pool of 18 high risk HPV probes using an automated stainer; p16 immunohistochemistry (IHC) was also performed. We conducted a literature review on HPV detection methods including p16 IHC, mRNA ISH, DNA ISH, and PCR. RESULTS: In our cohort, mRNA ISH had a sensitivity and specificity of 100% and 100% with reference to p16 (100% concordance). 2-year OS was 87.5% vs. 94.5% for p16/HPV-negative vs. positive patients. 2-year DFS was 60.0% vs. 84.2%. On literature review, mRNA ISH demonstrated consistently high sensitivity and specificity ranging from 88-98% and 90-100% respectively. In comparison, the specificity of p16 was 85-95%. CONCLUSIONS: Our report supports the use of mRNA ISH for HPV detection in OPSCC and validates its feasibility using automated tissue staining methods on FFPE tissue. Our findings and literature review support that mRNA ISH may have superior specificity and be easier to interpret than p16. Further study on the prognostic value and cost-effectiveness of mRNA ISH is warranted and may establish this HPV detection method as the "gold standard."
Subject(s)
Alphapapillomavirus/genetics , Alphapapillomavirus/isolation & purification , Carcinoma, Squamous Cell/virology , In Situ Hybridization/methods , Oncogene Proteins, Viral/genetics , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , RNA, Messenger/analysis , RNA, Viral/analysis , Aged , Biomarkers/analysis , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk , Sensitivity and SpecificityABSTRACT
Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.
Subject(s)
Adenocarcinoma, Sebaceous/therapy , Evidence-Based Medicine/standards , Practice Guidelines as Topic/standards , Sebaceous Gland Neoplasms/therapy , Humans , PrognosisABSTRACT
The success of programmed cell death 1 (PD-1) inhibition in achieving a clinical response in a subset of head and neck squamous cell carcinoma (HNSCC) patients emphasizes the need to better understand the immunobiology of HNSCC. Immunophenotyping was performed for 30 HCSCC patients [16 human papillomavirus (HPV)-positive; 14 HPV-negative] on matched tissue from the primary tumour site, locally metastatic cervical lymph nodes (LNs), uninvolved local cervical LNs, and peripheral blood. CD4+ and CD8+ T-cell lymphocytes obtained from tissue were analysed for expression levels of the inhibitory receptors PD-1, TIM-3 and CTLA-4. Next-generation sequencing of the T-cell receptor (TCR) ß chain was performed on patients (n = 9) to determine receptor repertoire diversity and for clonality analysis. HPV-negative HNSCC patients, particularly those with stage IV disease, had significantly higher proportions of CD8+ T cells expressing CTLA-4 in tumour tissue (P = 0.0013) and in peripheral blood (P = 0.0344) than HPV-positive patients, as well as higher expression levels of TIM-3+ PD-1+ CD8+ T cells (P = 0.0072) than controls. For all patients, PD-1 expression on CD8+ T cells - particularly in HPV-negative HNSCC cases - strongly correlated (r = 0.63, P = 0.013) with tumour size at the primary site. The top CD8+ TCR clones from tumour tissue significantly overlapped with circulating peripheral blood TCR clones (r = 0.946), and HPV-positive patients had frequently expanded TCR clones that were more hydrophobic - and potentially more immunogenic - than those from HPV-negative patients. Collectively, our findings demonstrate, for the first time, that high-stage HPV-negative HNSCC patients with primary tumours at different sites in the head and neck have elevated peripheral CTLA-4+ CD8+ T-cell levels, that tumour-familiar CD8+ T cells are detectable in peripheral blood from HNSCC patients, and that TCRs from HPV-positive HNSCC patients potentially recognize distinctly immunogenic cognate antigens. However, our findings are preliminary, and need to be further confirmed in a larger patient cohort; also, how these factors affect patient response to immunotherapy needs to be determined. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Lymphocyte Activation/immunology , T-Lymphocytes/virology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/immunology , High-Throughput Nucleotide Sequencing/methods , Humans , Immunophenotyping , Male , Middle Aged , Papillomaviridae , Squamous Cell Carcinoma of Head and Neck , T-Lymphocytes/immunologyABSTRACT
BACKGROUND: The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. METHODS: The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. RESULTS: In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). CONCLUSIONS: Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society.
Subject(s)
Head and Neck Neoplasms/therapy , Quality Assurance, Health Care/methods , Quality Indicators, Health Care/standards , Adult , Aged , Combined Modality Therapy , Databases, Factual/statistics & numerical data , Female , Head and Neck Neoplasms/epidemiology , Humans , Interdisciplinary Studies , Male , Middle Aged , Retrospective Studies , United States/epidemiologyABSTRACT
BACKGROUND: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and HPV-negative tumors. METHODS: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n=21 HPV DNA-positive, n=19 HPV DNA-negative). CD3 and CD8 T-cell immunostaining were performed on whole-slide sections to quantify tumor-infiltrating lymphocyte (TIL) density and assess its morphology. RESULTS: A subset of cases (HPV-positive) displayed a unique TIL pattern consisting of circumferential peritumoral population T cells, which was absent in the HPV-negative cases. The presence of peritumoral cuffing was strongly predictive of improved recurrence-free survival compared to cases that lacked this morphologic pattern of immune infiltrate. Four HPV-positive cases lacked the pattern, including two cases with disease recurrence. CONCLUSIONS: For the first time, we show an architectural pattern of immune infiltrate in HNSCC is seen exclusively in HPV-positive patients with improved recurrence-free survival and suggests an organized host immunological response contributes to disease control.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/virology , Lymphocytes, Tumor-Infiltrating , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Papillomaviridae , Papillomavirus Infections/complications , T-Lymphocytes , Tongue Neoplasms/pathology , Tongue Neoplasms/virology , Carcinoma, Squamous Cell/immunology , Diagnosis, Differential , Female , Head and Neck Neoplasms/immunology , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/immunology , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Tongue Neoplasms/immunologyABSTRACT
BACKGROUND: With increasing economic healthcare constraints and an evolving understanding of patient selection criteria and patient safety, outpatient thyroidectomy is now more frequently employed. However, robust statistical analyses evaluating outcomes and safety after outpatient thyroidectomy with matched comparisons to inpatient cohorts are lacking. METHODS: The 2011-2012 NSQIP datasets were queried to identify all patients undergoing thyroidectomy. Inpatient and outpatient procedures cohorts were matched 1:1 using propensity score analysis to assess outcomes. Outcomes of interest included surgical and medical complications, reoperation, mortality, and readmission. Univariate and multivariate analyses were utilized to identify predictors of these events. Relative risk ratios were calculated for adverse events between inpatient and outpatient cohorts. RESULTS: In total, 21,508 patients were identified to have undergone a thyroidectomy in 2011-2012. Inpatients and outpatients were matched 1:1 with respect to preoperative and operative characteristics, leaving 8,185 patients in each treatment arm. After matching, overall 30-day morbidity was rare with only 250 patients (1.53 %) experiencing any perioperative morbidity. 476 patients (2.91 %) were readmitted within 30-days of the operation. Both pre- and post-matching, inpatient thyroidectomy was associated with increased risks of readmission, reoperation, and any complication. CONCLUSIONS: Based on this comprehensive population-based study, outpatient thyroidectomy appears to be at least as safe as inpatient thyroidectomy. However, there are still differences in outcomes between inpatient and outpatient cohorts, despite statistical matching of preoperative and intraoperative variables. Future research needs to be spent identifying these as-of-yet unknown risk factors to resolve this discrepancy.
Subject(s)
Ambulatory Surgical Procedures , Thyroidectomy , Adult , Aged , Current Procedural Terminology , Female , Humans , Logistic Models , Male , Middle Aged , Outcome Assessment, Health Care , Patient Safety , Propensity Score , Quality Improvement , Thyroidectomy/methodsABSTRACT
These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Carbon/therapeutic use , Guidelines as Topic , Heavy Ion Radiotherapy/methods , Humans , Neutron Capture Therapy/methods , Proton Therapy/methodsABSTRACT
OBJECTIVE: There is a current paucity of large-scale, multi-institutional studies that explore the risk factors for major complications following parotidectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program participant use file was reviewed to identify all patients who had undergone parotidectomy between 2006 and 2011. Risk factors that predicted adverse events were estimated by using multivariate logistic regression. RESULTS: Of 2919 included patients, 202 patients experienced adverse outcomes within the first 30 days of surgery. These included surgical complications in 76 (2.6%) patients; medical complications in 90 (3.1%) patients; death in 7 (0.2%) patients; and reoperation in 77 (2.6%) patients. Predictors of any complication included disseminated cancer (odds ratio [OR] = 2.28; 95% confidence interval [CI], 1.05-4.95; P = .036) and increasing total relative value units (OR = 1.01; 95% CI, 1.00-1.02; P = .027). Active smoking was a major risk factor for surgical complications (OR = 1.81; 95% CI, 1.08-3.05; P = .025). Dyspnea (OR = 2.93; 95% CI, 1.37-6.27; P = .006) significantly predicted medical complications. CONCLUSION: Although complication rates after parotidectomy are generally low, avoidance of specific and nonspecific postoperative complications still remains an area for improvement. Future outcomes databases should include procedure-specific complications, including facial nerve injury.
Subject(s)
Parotid Diseases/surgery , Parotid Gland/surgery , Postoperative Complications , Adult , Aged , Dyspnea/complications , Humans , Logistic Models , Middle Aged , Parotid Diseases/complications , Parotid Diseases/pathology , Quality Improvement , Registries , Reoperation , Retrospective Studies , Risk Factors , Smoking , United StatesABSTRACT
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."
Subject(s)
Head and Neck Neoplasms/therapy , Combined Modality Therapy , Head and Neck Neoplasms/diagnosis , Humans , Neoplasm Staging , Quality of LifeABSTRACT
PURPOSE: Squamous cell carcinoma is a common entity among adult head and neck cancer patients, with many requiring reconstruction post resection. Conversely, this entity is rare among children with major reconstruction even more unique. This case and the concomitant review of literature highlight the intricacies of pediatric facial reconstruction. METHODS: The case described is of a 6-year-old African-American boy with poor dentition and a painful, 1.5 cm epiphytic lesion on the alveolar ridge of the left mandible. Incisional biopsy and computerized tomography were employed to obtain diagnosis and extent of disease. Surgical resection and reconstruction followed. RESULTS: Incisional biopsy confirmed the diagnosis of squamous cell carcinoma. Maxillofacial computerized tomography confirmed the extent of the mandibular lesion. After interdisciplinary discussion and weighing options with the family, a segmental mandibulectomy, neck dissection, and right fibula free flap reconstruction with titanium 2.0 mm metal plate fixation was performed. Re-examination post-operatively showed complete coverage of the defect and the ability to restore excised dentition. CONCLUSION: Squamous cell carcinoma within the pediatric population occurs less often than sarcomas, but may necessitate major reconstruction. Without rigid reconstruction, contracture may result. The current consensus favors microvascular bone reconstruction. However, a lack of consensus exists regarding the timing of dental rehabilitation.
Subject(s)
Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Mandible/surgery , Mandibular Neoplasms/surgery , Plastic Surgery Procedures , Carcinoma, Squamous Cell/diagnostic imaging , Child , Head and Neck Neoplasms/diagnostic imaging , Humans , Male , Mandibular Neoplasms/diagnostic imaging , Radiography , Squamous Cell Carcinoma of Head and NeckABSTRACT
PURPOSE: With enhancements in patient safety and improvements in anesthesia administration, outpatient thyroidectomy is now frequently undertaken as an outpatient procedure, with several peer-reviewed reports of safe implementation totaling over 4500 procedures since 2006. However, robust statistical analyses of predictors for readmission are lacking. METHODS: The 2011 NSQIP data set was queried to identify all patients undergoing thyroidectomy on an outpatient basis. Outcomes of interest included surgical and medical complications, reoperation, mortality, and readmission. Univariate and multivariate analyses were utilized to identify the predictors of these events. RESULTS: In total 5121 patients were identified to have undergone an outpatient thyroidectomy in 2011. Overall 30-day morbidity was rare with only 47 patients (0.92%) experiencing any perioperative morbidity. One hundred eleven (2.17%) patients were readmitted within 30 days of the operation. A history of COPD was the only preoperative comorbid medical condition that significantly increased a patient's risk for readmission (OR 3.73 95% CI 1.57-8.85, p=0.003). Patients with a surgical complication were more than 7 times as likely to be readmitted (OR 2.08-25.28, p=0.002), and those with a medical complication were over 19 times as likely to be readmitted (OR 7.32-50.78, p<0.001). CONCLUSIONS: Readmission after outpatient thyroidectomy is infrequent, and compares well with other outpatient procedures. The main identified risks include preoperative COPD and any of the generic postoperative complications tracked in NSQIP. As procedures continue to transition into outpatient settings and financial penalties associated with readmission become a reality, these findings will serve to optimize outpatient surgery utilization.
Subject(s)
Ambulatory Surgical Procedures , Patient Readmission , Thyroidectomy , Female , Forecasting , Humans , Male , Middle Aged , Postoperative Complications , Pulmonary Disease, Chronic Obstructive/complications , Reoperation , Risk Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real-world contribution of specific disparities. STUDY DESIGN: Retrospective cohort study. SETTING: United States. METHODS: The Centers for Disease Control and Prevention-Social Vulnerability Index (SVI) and National Cancer Institute-Surveillance, Epidemiology, and End Results Program database were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow-up and survival across social vulnerability and 4 subcategories of social vulnerability. RESULTS: As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow-up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores. CONCLUSION: Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.
Subject(s)
Carcinoma, Squamous Cell , Tongue Neoplasms , Humans , Tongue Neoplasms/pathology , Tongue Neoplasms/therapy , Tongue Neoplasms/mortality , Tongue Neoplasms/surgery , Male , Retrospective Studies , Female , Middle Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , United States/epidemiology , Prognosis , Aged , Social Determinants of Health , Adult , Vulnerable Populations , Survival Rate , SEER ProgramABSTRACT
These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).
Subject(s)
Head and Neck Neoplasms/therapy , Nutrition Policy , Eating , Enteral Nutrition , Humans , Practice Patterns, Physicians'ABSTRACT
OBJECTIVE: To quantify the price that private payers pay hospitals for head and neck squamous cell carcinoma (HNSCC) treatments and identify hospital-level factors associated with price variation. STUDY DESIGN: Cross-sectional study. SETTING: Price transparency files. METHODS: Files from the top 50 hospitals in otolaryngology according to the US News and World Report were analyzed between December 2021 and June 2022. This study analyzed the following Food and Drug Administration-approved HNSCC therapies: pembrolizumab, nivolumab, cetuximab, cisplatin, carboplatin, and paclitaxel. RESULTS: Twenty-four (48%) hospitals reported prices for at least 1 medication in our sample. Newer biologics were significantly more expensive than traditional chemotherapeutic agents. Given approved medication regimens, all biologics in our sample have similar annual costs. Price markups over acquisition costs ranged between 109% (pembrolizumab, nivolumab) and 530% for carboplatin. Across hospitals, prices varied the most for paclitaxel, the cheapest medication in our sample, and prices varied the least for pembrolizumab the most expensive medication in our sample. Hospital 340B status and geographic location in the northeast/west are associated with lower price markups. CONCLUSION: Price nondisclosure remains a significant problem among hospitals. Newer biological medications are more expensive when compared to traditional chemotherapeutic agents. Prices vary significantly across hospitals, with lower price markups observed in 340B hospitals as well as hospitals located in the geographic northeast and west. It remains to be seen if price transparency will lead to more uniform pricing or lower costs of treatments.
Subject(s)
Antineoplastic Agents , Biological Products , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Nivolumab , Carboplatin/therapeutic use , Cross-Sectional Studies , Head and Neck Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Paclitaxel , ImmunotherapyABSTRACT
Oral cancer is arguably the most serious condition that dental providers may encounter in their practice. The relatively poor prognosis associated with oral cancer highlights the importance of the dental team's awareness of the disease. While many characteristics of oral cancer have endured over time, new research is revealing trends that are changing the way we approach its screening, diagnosis and treatment. In this report, we provide a translational overview of oral cancer, including risk factors, signs and symptoms, clinical management, as well as our recent findings on the role of chronic inflammation in the development of the disease. In addition, our recent genetic profiling approach in both cancer cell lines and in patients has identified potential biomarkers, molecular pathways and therapeutic drugs for oral squamous cell carcinomas. This comprehensive review should be of interest to all dental professionals.
ABSTRACT
INTRODUCTION: The presence of tumor cell anaplasia and multinucleation (A/M) in oropharyngeal squamous cell carcinoma (OPSCC) has recently been found to be associated with increased disease recurrence and poorer disease-specific survival, regardless of human papillomavirus status. We studied the detection of A/M in cytology specimens. MATERIALS AND METHODS: We performed a comprehensive data search for all patients with OPSCC diagnosed and treated at Northwestern Memorial Hospital between January 2013 and April 2020. All cytology and histopathologic slides were reviewed for the presence of A/M in patients with both surgical resection or biopsy specimens and fine needle aspiration cytology of a metastatic site. RESULTS: A total of 87 patients were identified with both surgical and cytology specimens available for review. A/M was identified in 21 cytology specimens and 14 surgical specimens. Cytologic A/M was seen in 11 of the 14 patients (78.5%) with corresponding histologic A/M and in 10 of the 73 patients (13.7%) without histologic A/M. Disease-specific survival was significantly worse for the patients with cytologic A/M regardless of the presence of histologic A/M (P = 0.0064) and for the patients with cytologic A/M only (P = 0.0271). In patients with p16-positive/human papillomavirus-associated carcinoma, disease-specific survival was significantly worse for the patients with both histologic and cytologic A/M (P = 0.0305). CONCLUSIONS: A/M can be reliably identified in cytology specimens among all the various stains and preparations, irrespective of the primary tumor histologic type. Identification of A/M on cytology specimens could indicate more aggressive clinical behavior and help guide patient management.
Subject(s)
Alphapapillomavirus , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Anaplasia/complications , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/complications , Humans , Oropharyngeal Neoplasms/pathology , Papillomaviridae , Papillomavirus Infections/diagnosis , Squamous Cell Carcinoma of Head and Neck/complicationsABSTRACT
Oral squamous cell carcinoma (OSCC) is a major health problem worldwide, and patients have a particularly poor 5-year survival rate. Thus, identification of the molecular targets in OSCC and subsequent innovative therapies are greatly needed. Prolonged exposure to alcohol, tobacco, and pathogenic agents are known risk factors and have suggested that chronic inflammation may represent a potential common denominator in the development of OSCC. Microarray analysis of gene expression in OSCC cell lines with high basal NF-κB activity and OSCC patient samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation. In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated in OSCC. Moreover, IL-8 protein levels were significantly higher in OSCC cell lines as compared with normal human oral keratinocytes. Targeting IL-8 expression by siRNA significantly reduced the survival of OSCC cells, indicating that it plays an important role in OSCC development and/or progression. Inhibiting the inflammatory pathway by aspirin and the proteasome/NF-κB pathway by bortezomib resulted in marked reduction in cell viability in OSCC lines. Taken together our studies indicate a strong link between inflammation and OSCC development and reveal IL-8 as a potential mediator. Treatment based on prevention of general inflammation and/or the NF-κB pathway shows promise in OSCCs.
Subject(s)
Biomarkers/metabolism , Carcinoma, Squamous Cell , Inflammation/genetics , Mouth Neoplasms , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/therapeutic use , Aspirin/therapeutic use , Boronic Acids/therapeutic use , Bortezomib , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Cells, Cultured , Dose-Response Relationship, Drug , Gene Expression Profiling , Humans , Interleukin-8/genetics , Interleukin-8/immunology , Microarray Analysis , Mouth Neoplasms/drug therapy , Mouth Neoplasms/genetics , Mouth Neoplasms/immunology , NF-kappa B/metabolism , Pyrazines/therapeutic use , RNA, Small Interfering/metabolismABSTRACT
Oral cancer is arguably the most serious condition that dental providers may encounter in their practice. The relatively poor prognosis associated with oral cancer highlights the importance of the dental team's awareness of the disease. While many characteristics of oral cancer have endured over time, new research is revealing trends that are changing the way we approach its screening, diagnosis and treatment. In this report, we provide a translational overview of oral cancer, including risk factors, signs and symptoms, clinical management, as well as our recent findings on the role of chronic inflammation in the development of the disease. In addition, our recent genetic profiling approach in both cancer cell lines and in patients has identified potential biomarkers, molecular pathways and therapeutic drugs (Velcade and Aspirin) for oral squamous cell carcinomas. This comprehensive review should be of interest to all dental professionals.
Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Biomarkers, Tumor , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Humans , Inflammation/complications , Mouth Neoplasms/diagnosis , Mouth Neoplasms/etiology , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , Prognosis , Risk Factors , Sex Factors , Smoking/adverse effectsABSTRACT
BACKGROUND AND AIMS: Patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) experience vast disease and treatment burdens. Brief, focused instruments are needed to assess patient-reported priority symptoms and concerns as targeted outcome assessments for use in clinical research. Although the instrument was developed based on expert and patient input and is psychometrically valid, the Functional Assessment of Cancer Therapy (FACT)/National Comprehensive Cancer Network (NCCN) Head and Neck Symptom Index-10 (FHNSI-10) has yet to undergo content validation from the perspective of R/M SCCHN patients to evaluate its use as a brief symptom-focused targeted endpoint assessment for use in clinical research. METHODS: Interviews conducted with R/M SCCHN patients explored priority symptoms and concerns, followed by cognitive debriefing of the FHNSI-10 to evaluate face validity. Transcripts were analyzed, and results were mapped to the FHNSI-10. In accordance with published recommendations, expert input from the original development and published literature was considered for content validity assessment. RESULTS: A total of 18 patients participated in a concept elicitation interview; saturation was obtained at interview 17. Most (83%) were undergoing active treatment, male (94%), white (72%), and did not have a college degree (67%). The most commonly mentioned symptoms were lumps/swelling, pain, sore throat, difficulty swallowing, and voice changes. For all items, ≥75% reported each question was relevant to their R/M SCCHN experience and 94% reported the instrument captured their experiences with R/M SCCHN. CONCLUSION: Results provide support for the content validity of the FHNSI-10, inasmuch as all 10 items were spontaneously reported and considered relevant to R/M SCCHN. Content validity might be enhanced by adding cough and hearing impairment items; however, the existing FHNSI-10 covers the majority of symptoms uncovered in interviews with a small sample of R/M SCCHN patients.
ABSTRACT
OBJECTIVES: To develop and evaluate a simulation-based mastery learning (SBML) curriculum for cricothyrotomy using wet towels to suppress aerosolisation during a pandemic. DESIGN: Quasi-experimental, pre-post study. SETTING: Tertiary care, academic medical centre in Chicago. PARTICIPANTS: Ear, nose and throat and general surgery residents, fellows and attendings. INTERVENTION: Cricothyroidotomy simulation-based mastery learning curriculum. OUTCOMES MEASURE: Pretest to posttest simulated cricothyrotomy skills checklist performance. RESULTS: 37 of 41 eligible surgeons participated in the curriculum. Median pretest score was 72.5 (IQR 55.0-80.0) and 100.0 (IQR 98.8-100.0) for the posttest p<0.001. All participants scored at or above a minimum passing standard (93% checklist items correct) at posttest. CONCLUSIONS: Using SBML is effective to quickly train clinicians to competently perform simulated cricothyrotomy during a pandemic.