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Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive form of thyroid cancer. Increasingly, patients with ATC present with concurrent foci of well-differentiated thyroid carcinoma (WDTC); however, the significance of these pathologic findings remains unclear. The objective of this study is to determine whether the presence of WDTC within anaplastic tumors is a prognosticator of survival.A retrospective cohort study of all cases of biopsy-proven ATC managed at a tertiary care academic medical center from 2002 to 2020 was performed. Mean age at diagnosis, median survival time, and locations of distant metastases were assessed. The impact of clinical markers such as presence of differentiation, demographic variables, and oncologic information on overall survival was also determined via univariate and multivariate analysis.Forty-five patients were included in this study. The mean age at diagnosis was 69.1 years. Median survival time was 6.1 months after diagnosis. The most common location of distant metastases was the lung (40%). The presence of limited areas of WDTC in patients with predominantly anaplastic thyroid tumors was not significantly associated with improved outcomes (p = 0.509). Smaller tumor size and use of chemotherapy in ATC patients were significantly associated with prolonged survival (p = 0.026 and 0.010, respectively).Clinical outcomes for ATC remain poor. The presence of foci of differentiation within anaplastic thyroid tumors does not appear to improve overall survival-the anaplastic component evidently drives outcomes. Further studies into novel therapies are needed to improve survival in ATC.4 Laryngoscope, 2022.

Purpose of Review The complex and varied drainage patterns in the head and neck present a challenge in the regional control of cutaneous neoplasms. Lymph node involvement significantly diminishes survival, often warranting more aggressive treatment. Here, we review the risk factors associated with lymphatic metastasis, in the context of the evolving role of sentinel lymph node biopsy. Recent Findings In cutaneous head and neck melanomas, tumor thickness, age, size, mitosis, ulceration, and specific histology have been associated with lymph node metastasis (LNM). In head and neck cutaneous squamous cell carcinomas, tumor thickness, size, perineural invasion, and immunosuppression are all risk factors for nodal metastasis. The risk factors for lymph node involvement in Merkel cell carcinoma are not yet fully defined, but emerging evidence indicates that tumor thickness and size may be associated with regional metastasis. Summary The specific factors that predict a greater risk of LNM for cutaneous head and neck cancers generally include depth of invasion, tumor size, mitotic rate, ulceration, immunosuppression, and other histopathological factors.

Purpose: As a transcriptional repressor of E-cadherin, Snail has predominantly been associated with epithelial-mesenchymal transition, invasion, and metastasis. However, other important Snail-dependent malignant phenotypes have not been fully explored. Here, we investigate the contributions of Snail to the progression of nonsmall cell lung cancer (NSCLC).Experimental Design: Immunohistochemistry was done to quantify and localize Snail in human lung cancer tissues, and tissue microarray analysis was used to correlate these findings with survival. NSCLC cell lines gene-modified to stably overexpress Snail were evaluated in vivo in two severe combined immunodeficiency murine tumor models. Differential gene expression between Snail-overexpressing and control cell lines was evaluated using gene expression microarray analysis.Results: Snail is upregulated in human NSCLC tissue, and high levels of Snail expression correlate with decreased survival (P < 0.026). In a heterotopic model, mice bearing Snail-overexpressing tumors developed increased primary tumor burden (P = 0.008). In an orthotopic model, mice bearing Snail-overexpressing tumors also showed a trend toward increased metastases. In addition, Snail overexpression led to increased angiogenesis in primary tumors as measured by MECA-32 (P < 0.05) positivity and CXCL8 (P = 0.002) and CXCL5 (P = 0.0003) concentrations in tumor homogenates. Demonstrating the importance of these proangiogenic chemokines, the Snail-mediated increase in tumor burden was abrogated with CXCR2 blockade. Gene expression analysis also revealed Snail-associated differential gene expression with the potential to affect angiogenesis and diverse aspects of lung cancer progression.Conclusion: Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands. (Clin Cancer Res 2009;15(22):68209)

Supplementary Data from Snail Promotes CXCR2 LigandDependent Tumor Progression in NonSmall Cell Lung Carcinoma

Comprehensive education regarding human papillomavirus (HPV) pathogenesis, vaccination, and patient counseling are not routinely included in the medical school curriculum; consequently, student and provider knowledge, especially concerning head and neck pathology, remains low. The objective of this study was to demonstrate long-term retention of HPV knowledge and positive attitudes towards HPV vaccination after attending our novel HPV workshop, with a focus on knowledge of oropharyngeal cancer. A follow-up survey was administered to medical students 1.5 years after the initial completion of the workshop. HPV vaccination records from the student-led clinic were collected from the immunization information system. Awareness that HPV causes oropharyngeal cancer was present in 33% of medical students pre-curriculum; immediate and long-term post-curricular awareness of this association remained at 90% or higher (p

OBJECTIVE/HYPOTHESIS Utilization of flaps for reconstruction of large head and neck cancer (HNCA) defects has become more prevalent. The present study aimed to assess the impact of center experience as measured by annual hospital caseload on mortality, major complications, resource utilization, and 90-day readmissions following HNCA resection with flap reconstruction. STUDY DESIGN Non-Randomized Controlled Cohort Study. METHODS All adult patients undergoing elective HNCA resection with flap reconstruction were identified utilizing the 2010 to 2018 Nationwide Readmissions Database. Hospitals were subsequently classified as low-, medium-, or high-volume based on annual institutional surgical caseload tertiles. Multivariable regression models were implemented to assess the independent association of hospital volume with the outcomes of interest. RESULTS Over the nine-year study period, the proportion of HNCA resection with flap reconstruction gradually increased (12.8% in 2010 vs. 17.3% in 2018, P

The Radiation Therapy Oncology Group 91-11 trial and US Veterans Affairs trial revolutionized the way locally advanced laryngeal cancers are treated. Adjuvant therapies exist aimed toward laryngeal preservation using docetaxel, cisplatin, and fluorouracil. Cetuximab is a cornerstone of treatment due to the large role of epidermal growth factor receptor in laryngeal and hypopharyngeal carcinomas. In addition, the immune system is vital in the prevention of recurrence, and various immunomodulators against programmed cell death receptor 1 are being investigated. Multidisciplinary management of the patient with laryngeal and hypopharyngeal is key, as many vital functions are affected by this devastating disease.

BackgroundRecent advances in artificial intelligence (AI) in the field of imaging have resulted in new opportunities for automated tumor detection and margin assessment. In particular, AI deep learning techniques such as the Convolutional Neural Network (CNN) have greatly advanced the field of computer vision. Here we introduce the application of a CNN model for use with Dynamic Optical Contrast Imaging (DOCI), an imaging technique developed by our group that creates a unique molecular signature on tissue targets by obtaining the autofluorescence decay of several spectral bands in the UV-Vis range.Methods21 patients undergoing surgical resection for tonsillar squamous cell carcinoma (SCC) were identified on a prospective basis. DOCI images were analyzed and compared to the pathology results as ground truth. A CNN model was used to segment sections of DOCI images and provide a percentage chance of tumor presence, allowing for automated tumor margin delineation without a-priori knowledge of the tumor tissue composition.ResultsCNN outputs yielded a 99.98% confidence in classifying non-tumor tissue and 76.02% confidence in classifying tumor tissue.ConclusionsOur results indicate that a CNN-based classification model for DOCI allows for real-time analysis of tissue, providing improved sensitivity and accuracy of determining true margins and thus enabling the head and neck cancer surgeon to save healthy tissue and improve patient outcomes.

OBJECTIVES/HYPOTHESIS To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN Retrospective database study. METHODS The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P

BACKGROUND Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. METHODS Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. RESULTS Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19). CONCLUSIONS Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings.

OBJECTIVES/HYPOTHESIS Identification of parathyroid glands and adjacent tissues intraoperatively can be quite challenging because of their small size, variable locations, and indistinct external features. The objective of this study is to test the efficacy of the dynamic optical contrast imaging (DOCI) technique as a tool in specifically differentiating parathyroid tissue and adjacent structures, facilitating efficient and reliable tissue differentiation. STUDY DESIGN Prospective study. METHODS Both animal and human tissues were included in this study. Fresh specimens were imaged with DOCI and subsequently processed for hematoxylin and eosin (H&E) stain. The DOCI images were analyzed and compared to the H&E results as ground truth. RESULTS In both animal and human experiments, significant DOCI contrast was observed between parathyroid glands and adjacent tissue of all types. Region of interest analysis revealed most distinct DOCI values for each tissue when using 494 and 572 nm-specific band pass filter for signal detection (P

To assess knowledge regarding head and neck cancers (HNCs) in 2020, factors associated with knowledge of the role of human papillomavirus (HPV) in HNCs, and factors associated with exposure to Oral, Head and Neck Cancer Awareness Week (OHANCAW).Cross-sectional survey.Online.The survey was distributed to 517 participants via a paid panel and utilized US Census-built quotas to represent the US population.Participants surpassed 50% awareness rates in only 5 of 10 (50.0%), 2 of 6 (33.3%), and 5 of 9 (55.5%) preselected answer choices for subsites, risk factors, and signs/symptoms of HNCs, respectively. Knowledge of HPV's role in oropharyngeal cancer was also low, at 30.6%. However, of the controlled variables, exposure to OHANCAW was closely associated with knowledge of HPV's role in HNC (odds ratio, 10.25; 95% CI, 5.36-19.62). Women and elderly individuals were less likely to be exposed to OHANCAW, while those with higher education, those who drink heavily (4 drinks/d), and current but not former tobacco users were more likely to be exposed.Knowledge of HNCs and the causal role of HPV remains suboptimal, though our results suggest that OHANCAW remains a viable educational pathway. However, certain at-risk populations, such as former smokers and older individuals, whom we may not be effectively reaching and screening, represent a priority for future outreach efforts.

There has been a drastic increase in the incidence of nonmelanoma (NMSC), including squamous, basal cell, and melanoma skin cancers worldwide. Most cases of skin cancer can be treated effectively with surgery; fewer than 10% of cases are advanced and may require additional therapies. A better understanding of the biology of skin cancer will help contribute to better prognostic information and identification of possible new therapeutic targets. Herein, the authors review the biology and pathogenesis of both NMSC and melanoma, focusing on critical cell signaling pathways mediating the disease and current therapeutic strategies targeted to underlying genetic pathways.

To determine demographic factors and clinicopathologic characteristics associated with survival in young patients (age45 years) with early- (I-II) or late-stage (III-IV) oral tongue squamous cell carcinoma (OTSCC).Retrospective database review.National Cancer Database.A retrospective review of 3262 OTSCC cases in young patients between 2005 and 2014 was performed by using data from the National Cancer Database. Factors affecting 2-year survival in patients with early- and late-stage disease were evaluated via univariate and multivariate analyses.Overall, 1899 patients with early-stage OTSCC and 1363 with late-stage OTSCC were analyzed. In multivariate analysis of early-stage OTSCC, high tumor grade (hazard ratio, 2.08 [95% CI, 1.45-2.99]), local metastasis (2.85 [1.37-5.95]), and tumor size (1.04 [1.02-1.07]) were predictors of mortality. In late-stage OTSCC, African American race (2.79 [1.40-5.56]), positive surgical margins (1.77 [1.07-2.93]), local metastasis (2.20 [1.03-4.72]), distant metastasis (11.66 [2.10-64.73]), depth of invasion (1.03 [1.01-1.05]), and tumor size (1.01 [1.003-1.01]) were predictors of mortality. Subset analysis of clinical N0-stage tumors revealed that treatment with surgery alone was associated with improved survival (Positive lymph nodes, high tumor grade, and larger tumor size were associated with increased mortality risk in early- and late-stage young OTSCC. More aggressive up-front treatment, including extirpative surgery and elective neck dissection, may be associated with improved outcomes and should be considered in early-stage cases with high-risk features.

Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the induction and activation of an immune response against cancer. Therapeutic vaccination, which can induce a specific immune response against tumor antigens, is an important approach to consider. Although this approach has shown low clinical efficacy when combined with other treatment modalities, therapeutic cancer vaccines will have a better outcome when combined with immune checkpoint blockade therapy with potential for cancer free survival. In this review, we will discuss the results of our two recent publications in preclinical lung cancer models. Our studies reveal that anti-PD-1 administered in combination with CCL21-DC tumor antigen therapeutic vaccines eradicate lung cancer. The results of these studies highlight the importance of combination therapy of immune checkpoint blockade and therapeutic cancer vaccines for lung cancer patients.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63–5.76; p 5 cm (HR: 2.29; 95% CI: 1.26–4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24–4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status (p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Purpose The role of chemoradiation (CRT) in treating patients with early-stage glottic squamous cell carcinoma (SCC), especially for T2N0M0 glottic SCC with impaired vocal cord mobility, remains unexplored. We sought to evaluate the impact of CRT on survival in early-stage glottic SCC by using the SEER database. Patients and Methods We included patients with localized (T1-4N0M0) glottic SCC (N = 4,743) diagnosed between 2004 and 2014 and treated with definitive radiotherapy (RT) alone, CRT, or laryngectomy alone in the SEER database. Disease-specific mortality (DSM) was evaluated via multivariable regression using a competing risk model that accounts for other-cause mortality as a competing risk event for DSM. One-to-one propensity score matching between CRT and RT cohorts was also performed to facilitate comparison of cumulative DSM and other-cause mortality incidences stratified by T stage. Results After stratification by T stage, CRT was associated with increased DSM in T1-2N0M0 glottic SCC (adjusted hazard ratios [AHRs], 4.222 and 2.260 for T1 and T2 disease, respectively; P < .001 for both). For T2N0M0 glottic SCC with and without impaired vocal cord mobility, CRT resulted in significantly increased DSM compared with RT alone in both cohorts (AHR, 2.084; P = .046 and AHR, 2.412; P < .001, respectively). After propensity score matching, cumulative incidence plots demonstrated a statistically significant increase in DSM associated with CRT compared with RT alone for both T1 and T2 glottic SCC ( P < .001 and P = .003, respectively). Conclusion CRT for T1-2N0M0 glottic SCC was associated with increased DSM compared with RT alone. This pattern persisted upon further stratification on the basis of vocal cord mobility status for T2N0M0 glottic SCC. This finding warrants careful consideration of chemotherapy in early-stage glottic SCC.

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk.

Cerebrospinal fluid (CSF) leaks can occur when there is a communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient’s risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions post operatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and non-invasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample is sent to a tertiary site for analysis where days to weeks may pass before results return. To address this, our group recently developed a semi-quantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-trace protein, which has been reported as an indicator of the presence of CSF leaks. In the work presented here, we created a rapid diagnostic test kit comprised of our LFA, a collection swab, dilution buffers, disposable pipettes, and instructions. Validation studies demonstrated excellent predictive capabilities of this kit in distinguishing between clinical specimens containing CSF and those that did not. Our diagnostic kit for CSF leak detection can be operated by an untrained user, does not require any external equipment, and can be performed in approximately 20 min, making it well-suited for use at the point-of-care. This kit has the potential to transform patient outcomes.

To evaluate the clinicopathologic characteristics of head and neck solitary fibrous tumors and features that may predict tumor recurrence.Retrospective review.University of California-Los Angeles Medical Center.A single-center retrospective study was conducted on pathologically confirmed cases of head and neck solitary fibrous tumors between 1996 and 2021. Patient demographics, clinical course, and histopathologic features were evaluated. Recurrence-free survival was estimated via Kaplan-Meier analysis.A total of 52 patients were reviewed. The average patient age was 54.7 years (range, 15-89). The most common subsite was the orbit (53.8%, n = 28), but other involved areas included the nasopharynx, paranasal sinuses, and scalp. The median tumor size was 2.95 cm (range, 1.3-11.2). Strong STAT6 (100%) and CD34 (97.9%) expression was observed on immunohistochemistry. Almost all patients were initially managed with wide local excision; 82% of patients (n = 14) had positive margins on pathologic review; and 15% (n = 4) had recurrence at a median 28.5 months (range, 10-113). White patient race was the only significant predictor of tumor recurrence. Patient age (≥55 years), tumor size (≥4), high mitotic rate, and disease subsite were not associated with recurrence.Head and neck solitary fibrous tumors demonstrate a significantly larger local recurrence rate as compared with their rate of metastasis. They can recur many years following initial therapy, warranting long-term surveillance and follow-up to assess for tumor recurrence.

Primary hyperparathyroidism, often caused by a single adenoma (80-85%) or four-gland hyperplasia (10-15%), can lead to elevated parathyroid hormone (PTH) levels and resultant hypercalcemia. Surgical excision of offending lesions is the standard of care, as the removal of pathologic adenomas reduces PTH and calcium values to baseline. The small size, variable location, and indistinct external features of parathyroid glands can make their identification quite challenging intraoperatively. Our group has developed the dynamic optical contrast imaging (DOCI) technique, a novel realization of dynamic temporally dependent measurements of tissue autofluorescence. In this study, we evaluated the efficacy of using the DOCI technique and normalized steady-state fluorescence intensity data for differentiating types of human parathyroid and thyroid tissues. We demonstrate that the DOCI technique has the capability to distinguish normal parathyroid tissue from diseased parathyroid glands as well as from adjacent healthy thyroid and adipose tissue across 8 different spectral channels between 405nm-600nm (p). Patient tissue DOCI data was further analyzed with a logistic regression classifier trained across the 8 spectral channels. After computer training, the computer-aided identification was able to accurately locate hypercellular parathyroid tissue with 100% sensitivity and 98.8% specificity within the captured DOCI image.

OBJECTIVES/HYPOTHESIS The current state of the U.S. public's knowledge of the relationship between human papillomavirus (HPV) and HPV vaccinations to oropharyngeal squamous cell carcinoma (OPSCC) is unknown. Our objective was to 1) assess the general population's knowledge of human papillomavirus (HPV) and willingness to vaccinate, and 2) assess whether targeted education on HPV-related OPSCC can change intentions to vaccinate. STUDY DESIGN Online cross-sectional survey. METHODS An online, cross-sectional survey utilizing U.S. census-derived quotas to represent the U.S. population was distributed and analyzed to 517 adults in 2020. RESULTS Exactly 72.7% of participants stated that they had or would vaccinate their child against HPV and were designated as "vaccinators." In multivariate regression, Black individuals were less likely to be vaccinators (OR 0.51 [95% CI 0.27-0.94]), but those who were aware of HPV's role in OPSCC were more likely to vaccinate (OR 2.56 [95% CI 1.47-4.46]). Knowledge about vaccination side-effects, eligibility, and mechanisms of HPV spread was low. Only 30.6% of the sample reported understanding the role of HPV in OPSCC. Of these, 43.0% gained this knowledge exclusively from nonhealthcare professional sources, like television. When presented with four short HPV-OPSCC-centered facts (HPV's role in OPSCC etiology, prevalence of infection, clinically silent course, and vaccine preventative effects), 54.0% of "nonvaccinators" indicated a willingness to change their minds. CONCLUSIONS General knowledge about HPV, HPV's role in OPSCC, and the vaccine remains low in the general population. There are racial disparities in willingness to vaccinate within this sample, but these may be overcome by effective education on HPV-related OPSCC. LEVEL OF EVIDENCE 3 Laryngoscope, 2021.

Objectives To evaluate the incidence, causes, risk factors, and costs associated with 30-day readmissions in parotidectomy patients utilizing the Nationwide Readmissions Database (NRD). Study design Retrospective cohort study. Methods We examined the NRD for patients who underwent parotidectomy between 2010 and 2014. Rates, causes, and costs of 30-day readmissions were determined. Multivariate logistic regression was used to identify risk factors for readmission. Results Among 15,102 included patients, 594 (3.9%) were readmitted within 30 days. The average cost per readmission was $12,502. Infectious (22.7%) and wound (11.2%) complications were the two most common causes of readmission. After controlling for other covariates, significant predictors of readmission included advanced comorbidity (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.09-2.37), a malignant parotid tumor (OR, 2.37; 95% CI, 1.63-3.43), length of stay ≥2 days (OR, 1.54; 95% CI, 1.09-2.18), and nonroutine discharge destinations (home with care [OR, 1.88; 95% CI, 1.27-2.78] and nursing facility [OR, 2.69; 95% CI, 1.55-4.67]). Conclusion In this nationwide database analysis, we found that nearly 4% of all patients undergoing parotidectomy are readmitted within 30 days. Readmissions are commonly due to infections and wound complications. Quality improvement proposals targeting avoidable readmissions should focus on early recognition and prevention of infection and wound complications. Risk factors contributing to readmission include advanced comorbidity, malignant parotid tumor, prolonged index hospitalization, and nonroutine discharge destinations. Level of evidence NA Laryngoscope, 130:1212-1217, 2020.

Background Survival outcomes for adjuvant chemoradiotherapy (aCRT) and adjuvant radiotherapy (aRT) were compared in patients with oropharyngeal squamous cell carcinoma (OPSCC) with intermediate-risk features. Methods We identified 2164 patients with OPSCC in the National Cancer Database without positive margins or extracapsular extension and with at least one intermediate-risk feature: pT3-T4 disease, ≥two positive lymph nodes, level IV/V nodal disease, and/or lymphovascular invasion. We assessed predictors of aCRT use and covariables impacting overall survival. Results aCRT was commonly used for both human papillomavirus (HPV)-positive (62.0%) and HPV-negative (64.3%) patients with OPSCC. Higher N stage, level IV/V neck disease, and younger age strongly predicted aCRT utilization. There was no significant survival benefit associated with aCRT vs aRT in HPV-positive (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.62-1.38; P = .71) or HPV-negative (HR, 0.75; 95% CI, 0.51-1.10; P = .15) disease. Conclusions Despite high rates of utilization, aCRT is not associated with better survival vs aRT for OPSCC with intermediate-risk features, including HPV-negative tumors.

IMPORTANCE: Thirty-day hospital readmissions have substantial direct costs and are increasingly used as a measure of quality care. However, data regarding the risk factors and reasons for readmissions in head and neck cancer surgery reconstruction are lacking. OBJECTIVE: To describe the rate, risk factors, and causes of 30-day readmission in patients with head and neck cancer following free or pedicled flap reconstruction. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study analyzed medical records from the Nationwide Readmissions Database of 9487 patients undergoing pedicled or free flap reconstruction of head and neck oncologic defects between January 1, 2010, and December 31, 2014. Data analysis was performed in October 2017. EXPOSURES: Pedicled or free flap reconstruction of an oncologic head and neck defect. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause readmissions. Secondary outcomes included risk factors, causes, and costs of readmission. Multivariate regression analyses were conducted to determine factors independently associated with 30-day readmissions. RESULTS: Among 9487 patients included in the study (6798 male; 71.7%), the median age was 63 years (interquartile range, 55-71 years), and the 30-day readmission rate was 19.4% (n = 1839), with a mean cost per readmission of $15 916 (standard error of the mean, $785). The most common indication for readmission was wound complication (26.5%, n = 487). On multivariate regression, significant risk factors for 30-day readmission were median household income in the lowest quartile (vs highest quartile: odds ratio [OR], 1.58; 95% CI, 1.18-2.11), congestive heart failure (OR, 1.68; 95% CI, 1.14-2.47), liver disease (OR, 2.02; 95% CI, 1.22- 3.33), total laryngectomy (OR, 1.40; 95% CI, 1.12-1.75), pharyngectomy (OR, 1.47; 95% CI, 1.08-2.01), blood transfusion (OR, 1.30; 95% CI, 1.04-1.64), discharge to home with home health care (vs routine: OR, 1.32; 95% CI, 1.04-1.67), and discharge to a nursing facility (vs routine: OR, 1.77; 95% CI, 1.30-2.40). CONCLUSIONS AND RELEVANCE: Using the Nationwide Readmissions Database, we demonstrate that approximately 1 in 5 patients undergoing head and neck cancer surgery reconstruction is readmitted within 30 days of surgery. Readmissions are most commonly associated with wound complications. Socioeconomic status, complex ablative procedures, and patient comorbidities are independent risk factors for readmission. These findings may be useful to clinicians in developing perioperative interventions aimed to reduce hospital readmissions and improve quality of patient care.

Purpose To investigate the prognostic value of pre-treatment immune parameters including white blood cell count (WBC) and circulating lymphocyte count (CLC) among patients with oropharyngeal carcinoma treated by radiation therapy. Methods and Materials A total of 136 consecutive patients were treated by radiation therapy for locally advanced (stage III/IV) squamous cell carcinoma of the oropharynx with known human papillomavirus (HPV) status. Medical records were reviewed to identify patients with documented pre-treatment laboratory bloodwork. The Kaplan-Meier method and linear regression models were used to evaluate the association between pre-treatment CBC and CLC values with survival endpoints. Results One hundred and eleven patients satisfied inclusion criteria. Median age was 62 years (range, 22–91). Eighty-four patients were HPV-positive (76%) and 27 (24%) were HPV-negative. There was no difference in WBC and CLC mean values at baseline between HPV-positive and HV-negative (p > 0.05, for both). Trends were detected in the HPV-positive cohort favoring patients with higher CLC, with respect to 2-year local-regional control (93% vs. 82%, p = 0.06) and distant control (88% vs. 82%, p = 0.10) using the median CLC as cut-off. HPV-positive patients with CLC values in the lowest quartile had inferior local-regional control compared to those in the upper 3 quartiles (69% vs. 89%, p = 0.01). Conclusion Low pre-treatment CLC was correlated with local-regional recurrence and distant failure among HPV-positive patients. These associations were not observed in the HPV-negative cohort.

Objectives/hypothesis To characterize the demographics, clinicopathologic characteristics, and treatment and reconstructive outcomes of patients who underwent total glossectomy STUDY DESIGN: Retrospective chart review at an academic tertiary-care medical center. Methods All patients who had undergone total glossectomy (as an individual procedure or as part of a more extensive resection) between January 1, 1995 and December 31, 2014 were included in the analysis. Patient characteristics and clinical outcomes were reviewed. Results Forty-eight patients underwent total glossectomy for oral tongue and base of tongue cancer. The mean age of the patients was 56 (range, 29-92 years). History of tobacco and heavy alcohol use was found in 76% and 11% of patients, respectively. The majority of patients had advanced cancer (91.7% at stage IV), and 60.4% had salvage therapy for recurrent disease. T4 disease comprised 81% of patients. Sixty percent had clinical or radiographic evidence of nodal metastasis. Reconstruction of the defect was performed with free flaps from the rectus abdominus (40%), fibula (25%), anterolateral thigh (23%), and other donor tissues. One- and 5-year survival rates were 42% and 26%, with locoregional and distant recurrence reported at 36% and 25%, respectively. Conclusions Total glossectomy for oncologic control is most commonly performed in patients who have stage IV cancers. Despite high reconstructive success rates, the likelihood of locoregional and distance recurrence was high. Most patients can communicate intelligibly and achieve decannulation, but swallowing outcomes remain guarded, especially considering previous irradiation and resection of the base of tongue. Level of evidence 4 Laryngoscope, 129:1087-1092, 2019.

Background The impact of treatment delays on survival in oropharyngeal cancer and whether the effect varies by human papillomavirus (HPV) status have yet to be defined. Methods Retrospective analysis of the survival impact of time from diagnosis to surgery (DTS), surgery to radiation (SRT), and duration of radiation (RTD) for patients in the National Cancer Database with resected oropharyngeal cancer who underwent adjuvant radiation from 2010 to 2014. Results We identified optimal thresholds of 30, 40, and 51 days for DTS, SRT, and RTD, respectively, with treatment times exceeding these thresholds associated with significantly worse overall survival. Prolonged SRT and RTD were associated with mortality regardless of HPV status, although rising DTS was only predictive among patients with HPV-negative tumors. Conclusions Treatment delays significantly impact survival in oropharyngeal cancer. The consequences of prolonged DTS may be stronger in HPV-negative than HPV-positive disease. These data serve as a foundation for future research and clinical management.

OBJECTIVES/HYPOTHESIS To utilize the Surveillance, Epidemiology, and End Results (SEER) database to elucidate differences in predictors of survival in oral tongue squamous cell carcinoma (OTSCC) as stratified by age and sex. STUDY DESIGN Retrospective, population-based database analysis. METHODS The SEER registry was utilized to calculate survival trends for patients with OTSCC between 1973 and 2012. Patient data were then stratified by age (≤40 years vs. >40 years) and sex, then analyzed with respect to race, stage, grade, and treatment modalities. Overall survival (OS) and disease-specific survival (DSS) were calculated and compared. RESULTS There were 16,423 cases of OTSCC identified, with 526 and 706 young female and male patients, respectively. Young female patients had improved OS and DSS as compared to young male patients (75% vs. 67% at 5 years), which is better than older patients (P < .001). Younger patients were more likely to receive surgery (P < .001) and combination surgery and radiation (P < .001) as compared to older patients. On multivariate analysis, tumor stage was uniformly associated with worse OS and DSS (P < .05), with surgery predicting improved OS and DSS in all groups except young females (P < .05). Higher tumor grade predicted worse OS and DSS in older patients, but not younger patients (P < .05). CONCLUSIONS OTSCC appears to present with relatively heterogeneous characteristics across different age groups and sexes. Despite the rising incidence of OTSCC in young individuals, our study demonstrates that young patients have improved survival rates compared to older patients. LEVEL OF EVIDENCE NA Laryngoscope, 129:2076-2081, 2019.

Objective To examine the clinicopathologic factors that contribute to regional and distant recurrence in intermediate to high risk head and neck melanoma patients after sentinel lymph node biopsy (SLNB). Methods This study is a retrospective review from an academic tertiary care center. Patients treated with SLNB for head and neck melanoma from 1997 to 2019 were reviewed and characterized by sentinel lymph node (SLN) status. Clinical variables were examined for the impact on regional and distant recurrence in SLNB‐negative patients using univariable and multivariable Cox regression analysis. Results One hundred and fifty four patients were included. Of note, 127 (82.5 %) were men, and the average age was 61.3 years. Median follow‐up was 68.6 weeks. Pathologic review of SLNs found 3.9% positive for metastatic melanoma; 96.1% were negative. Regional recurrence was significantly associated with tumor stage and age on multivariate analysis. A total of 4.5% of patients recurred in a previously labeled negative basin. Scalp subsite accounted for 30.5% of primary tumors and was more likely to yield a positive SLN on univariate analysis (P = .023). Tumor stage and age were significantly associated with distant metastasis on multivariable analysis (P = .026, P