The impact of COVID-19 and vaccination status on outcomes in veterans with head and neck squamous cell carcinoma.

BACKGROUND: The impact of both COVID-19 infection and vaccination status on patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. OBJECTIVE: To determine the impact of COVID-19 infection and vaccination status on 60-day mortality, cardiovascular, and respiratory complications in patients with a prior diagnosis of HNSCC. METHODS: This was a retrospective cohort study through the Veterans Affairs (VA) Corporate Data Warehouse of Veterans with HNSCC who were tested for COVID-19 during any inpatient VA medical center admission. A cohort of patients was created of Veterans with a diagnosis of HNSCC of the oral cavity,oropharynx, hypopharynx, larynx, and nasopharynx based on International Classification of Disease (ICD) codes. Data collected included clinical/demographic data, vaccination status, and incidence of 60-day mortality, 60-day cardiovascular complication (including myocardial infarction, venous thromboembolism, cerebrovascular accident), and 60-day respiratory complication (including acute respiratory failure, acute respiratory distress syndrome, and pneumonia). The interactions between COVID-19 infection, vaccination status, morbidity and mortality were investigated. RESULTS: Of the 14 262 patients with HNSCC who were tested for COVID-19 during inpatient admission, 4754 tested positive (33.3%), and 9508 (67.7%) tested negative. Patients who tested positive demonstrated increased 60-day mortality (4.7% vs. 2.0%, respectively; p < 0.001), acute respiratory failure (ARF; 15.4% vs. 7.1%, p < 0.001), acute respiratory distress syndrome (ARDS; 0.9% vs. 0.2%, p < 0.001), and pneumonia (PNA; 20.0% vs. 6.4%, p < 0.001) compared to those who never tested positive, respectively. Patients who received COVID-19 vaccination between 2 weeks and 6 months prior to a positive test demonstrated decreased rates of ARF (13.2% vs. 16.0%, p = 0.034) and PNA (16.7% vs. 20.9%, p = 0.003) compared to the unvaccinated group. A logistic regression of patients with COVID-19 infections who died within 60 days was performed, with no significant survival advantage among patients vaccinated between 2 weeks and 6 months prior to the positive test. CONCLUSION: COVID-19 infection may significantly increase rates of 60-day mortality and respiratory complications in patients with HNSCC. COVID-19 vaccination between 2 weeks and 6 months prior to infection may decrease severity of respiratory complications but did not show significant mortality benefits in this study. These data highlight the need for surveillance of respiratory infection and vaccination in this vulnerable population.

Risk of post-tonsillectomy hemorrhage among COVID-19 positive pediatric patients.

OBJECTIVE: COVID-19 infection has been demonstrated to increase risk for post-operative bleeding. This study investigated the impact of COVID-19 infection on post-tonsillectomy hemorrhage in pediatric patients, a potentially devastating complication. STUDY DESIGN: Retrospective cohort study. METHODS: The TriNetX database was queried for pediatric patients who underwent tonsillectomy and evaluated for outcomes of primary and secondary post-tonsillectomy hemorrhage. RESULTS: Among subjects 18 years and younger, 1226 were COVID-19 positive and 38,241 were COVID-19 negative in the perioperative period. There was statistically significant increased risk of bleeding with perioperative COVID-19 infection at postoperative days 1, 5, and 10. Additionally, when assessing the role of COVID-19 infection before or after surgery, the risk of bleeding remained statistically significant at all three time points, however these results did not suggest that infection before surgery confers more/less risk compared to infection after. CONCLUSION: The results of this investigation suggest that the presence of COVID-19 in the perioperative period may pose an increased risk for acute or delayed post tonsillectomy hemorrhage. This study employed a large, diverse population and is the first to address this clinical question.

Correcting for Rater Effects in Operating Room Surgical Skills Assessment.

OBJECTIVE: To estimate and adjust for rater effects in operating room surgical skills assessment performed using a structured rating scale for nasal septoplasty. METHODS: We analyzed survey responses from attending surgeons (raters) who supervised residents and fellows (trainees) performing nasal septoplasty in a prospective cohort study. We fit a structural equation model with the rubric item scores regressed on a latent component of skill and then fit a second model including the rating surgeon as a random effect to model a rater-effects-adjusted latent surgical skill. We validated this model against conventional measures including the level of expertise and post-graduation year (PGY) commensurate with the trainee's performance, the actual PGY of the trainee, and whether the surgical goals were achieved. RESULTS: Our dataset included 188 assessments by 7 raters and 41 trainees. The model with one latent construct for surgical skill and the rater as a random effect was the best. Rubric scores depended on how severe or lenient the rater was, sometimes almost as much as they depended on trainee skill. Rater-adjusted latent skill scores increased with attending-estimated skill levels and PGY of trainees, increased with the actual PGY, and appeared constant over different levels of achievement of surgical goals. CONCLUSION: Our work provides a method to obtain rater effect adjusted surgical skill assessments in the operating room using structured rating scales. Our method allows for the creation of standardized (i.e., rater-effects-adjusted) quantitative surgical skill benchmarks using national-level databases on trainee assessments. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Impact of Early Research Productivity on Future Academic Output Among Head and Neck Fellows.

OBJECTIVE: To examine the impact of pre-fellowship publications on future research productivity and career placement among head and neck (H&N) surgery fellowship graduates. METHODS: H&N surgery fellowship graduates between 2014 and 2022 were identified from publicly available data. Timing of fellowship graduation, number of publications during each stage of education and training, and number of first authorship publications were analyzed for association with scholarly productivity and academic career placement. RESULTS: In our analysis of 409 H&N fellowship graduates, there was a strong positive correlation between the year of fellowship graduation and the average number of publications in residency (R2 = 0.82) and fellowship (R2 = 0.79). Graduates producing more than the average of 2.37 publications prior to residency had a significantly higher average number of publications during residency and fellowship compared to those who published below average (p < 0.001). A higher number of publications prior to and during residency were both independently associated with a higher likelihood of academic career placement (p = 0.015 and p = 0.002, respectively). More first-author publications prior to residency were associated with a higher number of publications during residency and fellowship (p = 0.015). In sub-analyses, gender did not impact the average number of publications during residency and fellowship. Similarly, the COVID-19 pandemic did not significantly impact the average number of publications during the fellowship when comparing the classes of 2020-2022 to 2017-2019. CONCLUSION: Research productivity among H&N fellowship graduates has increased in recent years. Research productivity in medical school and residency is associated with scholarly output in later stages of training and academic career placement. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Complications of eustachian tube balloon dilation: Manufacturer and User Facility Device Experience (MAUDE) database analysis and literature review.

Objective: To provide an analysis of complications following eustachian tube balloon dilation as well as their treatments and outcomes. Data Sources: PubMed, Ovid Embase, and MAUDE Database. Review Methods: A systematic approach following PRISMA guidelines was used to identify publications pertaining to balloon dilation of the eustachian tube from PubMed and Ovid Embase databases was used. Once these publications were critically reviewed, the primary outcome extracted were reported complications. Additional complications were collected in the Manufacturer and User Facility Device Experience (MAUDE) database using the product class "eustachian tube dilation device" and searching through relevant manufacturers. Complications and outcomes were compared between these sources. Results: Fifty five full-length manuscripts involving 7155 patients were included and 98 complications reported for a 1.4% complication rate. The most frequently reported adverse events were subcutaneous emphysema of the head and neck (19%), epistaxis (12%), and acute otitis media (11%). The MAUDE search returned 18 distinct patient entries, of which 12 (67%) reported complications. The most reported complications in the MAUDE database included subcutaneous emphysema (8, 67%) and pneumomediastinum (3, 25%). The most serious complication was a carotid artery dissection reported in one patient in the MAUDE database. Conclusion: Eustachian tube dilation is rarely associated with complications, which nevertheless may lead to morbidity and medical emergencies. Patients and providers should recognize potential risks associated with this intervention as well as methods to manage complications.

Perioperative complications among head and neck surgery patients with COVID-19.

BACKGROUND: Patients undergoing surgery for head and neck cancer (HNC) have potentially high perioperative complication rates. Recent studies indicate that preoperative COVID-19 infection poses increased risk for postoperative complications in other fields. However, to date, there has not been data showing the effect of COVID-19 on complication rates for HNC. Here, a large database was employed to assess if perioperative COVID-19 increased the risk of perioperative complications among those undergoing HNC surgery. METHODS: A retrospective investigation was conducted using a multi-institutional research database. Subjects who underwent HNC surgery from January 2020 to September 2022 were identified using the International Classification of Diseases and Current Procedure Terminology codes. Thirty-day surgical and medical complications were assessed for those diagnosed with COVID-19 infection from 7 days before or after surgery compared to those who were COVID-19 negative. Cohorts were propensity scores matched by age, sex, and race. RESULTS: Perioperative COVID-19 was present in n = 208 and absent in n = 15 158 subjects that underwent HNC surgery. For unmatched analyses, there was a statistically significant increased risk in the 30-day postoperative period in COVID-19-positive patients for the following surgical complications: surgical site fistula, free tissue transfer (FTT) complication, FTT failure, and death. Additionally, there was a statistically significant increased risk in the 30-day postoperative period in COVID-19-positive patients for the following medical complications: ventilator support, pneumonia, vasopressor, acute renal failure, and myocardial infarction. CONCLUSION: This large, retrospective populational study suggests HNC patients are at increased risk for death and several perioperative complications. This investigation is the first to address this clinical question.

Predictors of Survival in Veterans with Head and Neck Cancer Treated Surgically.

Background: Squamous cell carcinoma (SCC) accounts for 90% of all head and neck cancers. In veterans, the prevalence of head and neck SCC is nearly twice as high compared with the civilian population. Neck dissection plays an important role in the treatment algorithm for patients with head and neck SCC. The aim of this manuscript was to investigate predictors of survival in patients with head and neck SCC who underwent curative treatment. Methods: Patients with head and neck SCC who underwent treatment with curative intent were included in this study. Data collected included clinical-demographic characteristics, tumor characteristics, and outcome. The primary endpoint was 3-year overall survival (OS), and the secondary endpoints were disease recurrence and distant metastases. Results: A total of 149 patients met inclusion criteria, and most patients were treated with surgery plus adjuvant chemoradiation (52%). The 3-year OS for the entire cohort was 55.7%. There was no statistically significant difference in mortality when comparing the various treatment types. Black patients (hazard ratio [HR] = 1.70, P = .023) and other non-white patients (HR = 3.88, P = .027) had worse 3-year OS compared with white patients. Advanced tumor classification (T4a) was also associated with worse 3-year OS (HR = 3.088, P = .003) and increased risk of cancer recurrence or distant metastases (HR = 3.34, P = .013). Conclusions: Risk factors linked to poor survival among this cohort of veterans with head and neck SCC included non-white race and advanced tumor classification. Neck dissection remains an integral aspect of the treatment algorithm for SCC of the head and neck and can provide regional control of malignant disease.

Distant metastases in human papillomavirus-related oropharyngeal squamous cell carcinoma: Systematic review and meta-analysis.

The prevalence of distant metastases (DM) in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains unknown. A PRISMA systematic review of DM rates in patients with HPV-related OPSCC was performed. PubMed-MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched. The primary outcome was prevalence of DM. Data on demographics, tumor classification, and clinical outcomes were also collected. Meta-analysis of pooled DM rate was determined. Ten articles met inclusion criteria, representing 1860 patients with mean follow-up of 3.6 years. Overall DM rate was 7.0% (95% CI: 5.9-8.2). T3 or T4 classification disease was associated with a 4.88-fold (95% CI: 1.92-12.40) risk of DM compared to T1 or T2 classification disease. This study is the first to systematically review the prevalence of DM among patients with HPV-related OPSCC, where pooled DM rate was found to be 7%.

Malnutrition universal screening tool predicts postoperative complications following major head and neck cancer surgery.

BACKGROUND: Head and neck cancer patients are at risk for malnutrition, which can impact postoperative outcomes. This study evaluates the Malnutrition Universal Screening Tool (MUST) to predict outcomes in major head and neck surgeries. METHODS: A retrospective chart review included 275 major surgical procedures performed on 242 patients over the age of 18 years between May 2015 and May 2020. RESULTS: The majority of patients had a MUST score of zero (68.7%). Just under 17% scored 2 or greater indicating malnourishment. Having a MUST score of 2 or higher was associated with occurrence of a postoperative complication (p < 0.001). Patients with alcohol use disorder or depression were 5.2 (CI: 2.0-13.7, p = 0.001) and 2.75 (CI 1.1-7.0; p = 0.033) times more likely to develop a postoperative complication, respectively. CONCLUSIONS: Malnutrition and comorbidities were associated with complications in our surgical cohort. MUST is a novel tool to identify patients who may benefit from nutritional interventions.

Upper Airway Manifestations of Monkeypox: A Case Report and Literature Review.

Background: The monkeypox virus (MPXV) has spread globally, causing an infection similar to that of smallpox. In July 2022, MPXV was declared an international public health emergency by the World Health Organization. Although the prodromal and cutaneous symptoms are described, the literature is lacking with regard to the upper airway manifestations of the disease. Methods: This case report describes a 39-year-old gentleman with a history of human immunodeficiency virus who presented to the emergency department with fever, sore throat, and cough. A literature review was also performed to determine the clinical presentation and physical examination findings of patients presenting with MPXV. Results: The patient underwent flexible laryngoscopy on two separate occasions due to his symptoms of fever and sore throat. He was noted to have white plaque-like lesions throughout the upper aerodigestive tract that could not be excised with manipulation. Ultimately, he tested positive for MPXV and was treated with full recovery. Conclusions: To our knowledge, this is the first report describing upper airway manifestations of MPXV. Since patients with MPXV often present initially with pharyngitis, understanding the physical examination findings of MPXV in the upper airway is imperative for early diagnosis and public health awareness.

The impact of COVID-19 on presentation and diagnosis of head and neck squamous cell carcinoma.

Objective: To analyze how the COVID-19 pandemic has influenced trends in head and neck squamous cell carcinoma (HNSCC) presentation and diagnosis-including referral patterns, stage at presentation, and time to diagnosis-over a longitudinal time course. Setting: Multicenter tertiary care academic institution. Methods: A retrospective review of patients with HNSCC presenting between January 1, 2019 and December 31, 2020 was performed. Patients were stratified into pre-COVID and COVID cohorts based upon presentation date either before or after the COVID pandemic was declared a national emergency. Data was collected on demographics, referral site, symptoms, tumor characteristics, and time to diagnosis. Results: Of 203 patients with HNSCC identified, 77.3% (157/203) were in the pre-COVID cohort and 22.7% (46/203) were in the COVID cohort. Patients in the COVID cohort were more likely to present through inpatient or ER consultation (26% vs. 11%) than outpatient setting. There was a greater than 50% decrease in new tumor board case presentations per month in the COVID cohort (4.8) relative to the pre-COVID (10.9) cohort. Cancer stage at presentation was similar between cohorts. Time from presentation to diagnosis was similar between the cohorts at approximately 30 days. Conclusions: These results suggest that patients presenting during the COVID pandemic may have unique referral patterns. A significant decrease in tumor board presentations was noted, which may contribute to more delayed presentations that have yet to be observed. Further investigation with a larger sample size is warranted. Lay Summary: The COVID-19 pandemic may have changed where and how patients with head and neck cancer initially seek care. We found that patients with newly diagnosed head and neck cancer more often were initially seen in urgent settings than before the pandemic. Level of Evidence: 3.

Skull Base Regeneration During Treatment With Chemoradiation for Nasopharyngeal Carcinoma: A Case Report.

Background: Advanced cases of nasopharyngal carcinoma can present with skull base invasion. Treatment of these advanced cases with radiotherapy poses a challenge given proximity of tumor to critical neural structures as well as concern that a skull base defect and associated complications could develop with tumor regression. Case Presentation: A 34-year-old male patient presented with a 7-cm nasopharyngeal tumor invading the skull base with destruction of the clivus and intracranial extension. He underwent a course of definitive chemoradiation, requiring use of adaptive radiotherapy, that resulted in complete tumor regression and is free of disease 5 years posttreatment. Imaging done during treatment demonstrated that significant regeneration of bone occurred simultaneously with tumor regression. Conclusions: This case demonstrates that it is possible for bony regeneration to occur simultaneously with tumor regression in a patient with skull base invasion by tumor, precluding the need for neurosurgical intervention.

Do Attending and Trainee Surgeons Agree on What Happens in the Operating Room During Septoplasty?

Background: Surgeons must select cases whose complexity aligns with their skill set. Objectives: To determine how accurately trainees report involvement in procedures, judge case complexity, and assess their own skills. Methods: We recruited attendings and trainees from two otolaryngology departments. After performing septoplasty, they completed identical surveys regarding case complexity, achievement of goals, who performed which steps, and trainee skill using the septoplasty global assessment tool (SGAT) and visual analog scale (VAS). Agreement regarding which steps were performed by the trainee was assessed with Cohen's kappa coefficients (κ). Correlations between trainee and attending responses were measured with Spearman's correlation coefficients (rho). Results: Seven attendings and 42 trainees completed 181 paired surveys. Trainees and attendings sometimes disagreed about which steps were performed by trainees (range of κ = 0.743-0.846). Correlation between attending and trainee responses was low for VAS skill ratings (range of rho = 0.12-0.34), SGAT questions (range of rho = 0.03-0.53), and evaluation of case complexity (range of rho = 0.24-0.48). Conclusion: Trainees sometimes disagree with attendings about which septoplasty steps they perform and are limited in their ability to judge complexity, goals, and their skill.

Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma.

BACKGROUND: Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC). METHODS: A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical-demographic data, BMI, and outcomes. RESULTS: HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3-year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI. CONCLUSIONS: Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.

The distribution of parotid gland neoplasms in a veteran population.

OBJECTIVE: Salivary gland tumors account for 6%-8% of head and neck neoplasms with the parotid gland as the most common primary site. Pleomorphic adenomas (PA) are considered the most common benign parotid gland neoplasms, followed by Warthin tumors (WT). The goal of this study was to investigate the distribution of parotid gland neoplasms among a United States veteran population. DESIGN: Retrospective chart review. SETTING: Washington DC Veterans Affairs Medical Center. PARTICIPANTS: Veterans who underwent fine needle aspiration (FNA) for a parotid gland mass from 2000 to 2018 were included. Medical records were reviewed for gender, age, tobacco use, surgery date, and pathology results. MAIN OUTCOME MEASURES: Changes in the distribution of parotid neoplasms and tobacco use over an 18-year period. RESULTS: Of 141 patients with parotid gland masses, 86.5% (n = 122) were benign, 9.9% (n = 14) were malignant, and 3.5% (n = 5) were indeterminate. Of benign tumors, WT accounted for the majority at 51.6%, followed by PA at 40.2%. When stratified by decade (2000-2009 and 2010-2018), the proportion of WT compared to all other benign and malignant neoplasms increased from 31.6% to 53.6%, whereas the proportion of PA decreased from 36.8% to 33.3%. The rate of tobacco use was unchanged at approximately 32.0% among our cohort from 2000 to 2018. CONCLUSION: Among our cohort of veteran patients, WT was the most common benign parotid tumor and has increased in incidence over the last two decades despite an unchanged smoking rate.

Aspirin use predicts prolonged survival in patients with oropharyngeal cancer: Nationwide Veterans Affairs database study.

BACKGROUND: Single-institution studies suggest that aspirin reduces the risk of death in head and neck cancer. The aim of this study was to investigate the effect of aspirin use on overall survival (OS) in veterans with oropharyngeal cancer (OPC). METHODS: A total of 23 083 veterans with OPC were identified between 2005 and 2018 from the Veterans Health Administration Corporate Data Warehouse. Records were queried for clinical-demographic data, aspirin prescriptions, and outcomes. Three-year OS was estimated. A Cox model was used to estimate hazard ratios (HR) for aspirin use. RESULTS: Among the 23 083 identified veterans, 17 206 veterans met inclusion criteria. 21.8% used aspirin. Three-year OS was prolonged for aspirin users (66%) compared to nonaspirin users (54%; P < .001). Adjusted HR for death for nonaspirin users was 1.75 (95% confidence interval (CI) [1.60-1.91]). The average treatment effect of aspirin on survival using inverse probability weighting was 10% (95% CI [0.08-0.11]). CONCLUSION: Aspirin use following OPC diagnosis was independently associated with improved 3-year OS among veterans nationwide.

Surgical Considerations for an Awake Tracheotomy During the COVID-19 Pandemic.

Background: The current global COVID-19 pandemic is caused by the novel coronavirus Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Given that SARS-CoV-2 is highly transmissible, surgical societies have recommended that procedures with a high risk of aerosolization be avoided or delayed. However, some high-risk procedures, such as those related to head and neck malignancies, cannot always be delayed. Care must be taken during aerosol-generating procedures to minimize viral transmission as much as possible. Preoperative testing for COVID-19, limited operating room personnel, adequate personal protective equipment, and surgical technique are factors to consider for high-risk procedures. Methods: This article presents the case of an awake tracheotomy performed for a transglottic mass causing airway obstruction. Results: With detailed planning and specific techniques, the amount of aerosolization was reduced, and the procedure was performed as safely as possible. Conclusion: This case provides a template for future aerosol-generating procedures during respiratory pandemics.

Gender and compensation among surgical specialties in the Veterans Health Administration.

BACKGROUND: A gender pay gap has been reported across many professions, including medicine. METHODS: Surgeons employed at complex Veterans Affairs Medical Centers (VAMC) nationwide in 2016 were identified. Data on salary, gender, years since medical school graduation, professorship status, h-index, and geographic location were collected. RESULTS: Of 1993 surgeons nationwide, 23% were female. On average, female surgeons had significantly lower salaries compared to male surgeons ($268,429 ± 41,339 versus $287,717 ± 45,379, respectively; p < 0.001). Among each surgical specialty, there were no significant differences in salary on univariate analysis. Women were underrepresented in higher paying specialties and more heavily represented in lower paying specialties. On multivariate analysis, gender (p < 0.001), time since medical school graduation (p < 0.001), surgical specialty (p = 0.031), h-index (p < 0.001), and geographic location (p < 0.001) were significant predictors of salary. CONCLUSION: Female gender significantly predicted lower salary among VAMC surgeons, however within each surgical specialty, there was no significant gender pay gap. SENTENCE SUMMARY: Independent predictors of salary included gender, surgical specialty, experience, h-index, and geographic location. Although female surgeons had lower overall salaries compared to male surgeons in the Veterans Health Administration (VHA), there were no significant gender differences in salary among each surgical specialty. Pay transparency, unique to the VHA, along with the use of rational and objective criteria to establish and adjust salaries, may play a role in reducing the gender pay gap among VHA surgeons.

Inclusion of an E7 DNA Amplification Test Improves the Robustness of Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma Diagnosis.

BACKGROUND: The rise in human papillomavirus (HPV) infection rates over the last few decades in the USA has contributed to a significant increase in the overall incidence of patients diagnosed with squamous cell carcinoma of the head and neck. These head and neck carcinomas develop in the oropharynx, with more than 90% of them caused by infection with high-risk HPV type 16. Patients diagnosed with HPV-induced oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis and treatment response than those diagnosed with head and neck cancers caused by alcohol consumption and tobacco use. To identify patients with HPV-positive OPSCC, new guidelines recommend positive staining of oropharyngeal tissues for p16 INK4a (p16) by immunohistochemistry (IHC). Herein we discuss the testing algorithm that was adopted to address discrepant results between p16 IHC and a DNA in situ hybridization (ISH) test used routinely to diagnose HPV-positive OPSCC patients. METHODS: A DNA polymerase chain reaction (PCR) test that amplifies HPV16 and HPV18 E7 was developed to aid in the diagnosis of HPV-positive OPSCC in a subset of patients. Specimens from these patients stained positive for p16 by an IHC test, but negative for high-risk HPV by a commercial DNA ISH test. Moreover, these results did not match the histopathological characteristics of the specimens, nor the clinical presentations of the patients. RESULTS: Of 21 patients' specimens that were tested for p16 by IHC, 11 specimens showed concordant results with the high-risk HPV 16/18 DNA ISH test. Whereas, in eight p16 IHC positive specimens, HPV viral DNA was not detected by HPV16/18 DNA ISH, and two specimens were not tested by DNA ISH. When these eight p16 IHC positive specimens with discrepant p16 IHC and DNA ISH results were further tested by DNA PCR, six specimens showed concordance with p16 IHC with positive results for HPV16 E7, while two specimens were negative for HPV16 E7 by DNA PCR. All tested specimens were negative for HPV18 E7 by DNA PCR. Thus, the addition of the HPV16 and HPV18 E7 DNA PCR test identified a significant number of false negative test results by the HPV16/18 DNA ISH test and likely several false positive results by p16 IHC. CONCLUSIONS: Inclusion of an HPV16 E7 DNA PCR test improved the robustness of HPV-associated OPSCC diagnosis in patients with discrepant results from p16 IHC staining and a DNA ISH test, and identified patients for proper management with less misclassification.

Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer.

Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.