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Abstract BackgroundPrevious social determinants of health (SDoH) studies on laryngeal cancer (LC) have assessed individual factors of socioeconomic status and race/ethnicity but seldom investigate a wider breadth of SDoH-factors for their effects in the real-world. This study aims to delineate how a wider array of SDoH-vulnerabilities interactively associates with LC-disparities. MethodsThis retrospective cohort study assessed 74,495 LC-patients between 1975 and 2017 from the Surveillance-Epidemiology-End Results (SEER) database using the Social Vulnerability Index (SVI) from the CDC, total SDoH-vulnerability from 15 SDoH variables across specific vulnerabilities of socioeconomic status, minority-language status, household composition, and infrastructure/housing and transportation, which were measured across US counties. Univariate linear and logistic regressions were performed on length of care/follow-up and survival, staging, and treatment across SVI scores. ResultsSurvival time dropped significantly by 34.37% (from 72.83 to 47.80 months), and surveillance time decreased by 28.09% (from 80.99 to 58.24 months) with increasing overall social vulnerability, alongside advanced staging (OR 1.15; 95%CI 1.13–1.16), increased chemotherapy (OR 1.13; 95%CI 1.11–1.14), decreased surgical resection (OR 0.91; 95%CI 0.90–0.92), and decreased radiotherapy (OR 0.97; 95%CI 0.96–0.99). DiscussionIn this SDoH-study of LCs, detrimental care and prognostic trends were observed with increasing overall SDoH-vulnerability. 

Objective:Recurrent respiratory papillomatosis (RRP) is a rare disease of the airway for which there is no known cure. Treatment involves the surgical removal or destruction of these lesions. There has been a long-standing debate over the effectiveness of the adjuvant intralesional injection of the immune modifying agent bevacizumab. This study is a systematic review investigating the effect of adjuvant intralesional bevacizumab on patients with laryngeal papillomatosis. The main objective was to assess functional outcomes and efficacy. Data Sources:Pubmed, Google Scholar, and Web of Science. Review Methods:Search words were “intralesional bevacizumab” AND “recurrent respiratory papillomatosis.” Sources were systematically identified using inclusion and exclusion criteria (ie, study publication must post-date 2000, must be peer-reviewed, investigate patients with RRP, apply bevacizumab intralesionally, not systemically). Findings were then collected and analyzed. Results:Ten studies were included for analysis. The majority of these studies found an increase in the surgical interval, voice outcomes, and a decrease in tumor burden in most patients. No studies reported side effects or lasting complications related to the bevacizumab injection. Conclusion:This systematic review provides further evidence for the safety of intralesional bevacizumab injections and their likely positive effect on disease control. Future research would benefit from the implementation of standardized documentation of RRP outcomes. 

ObjectiveTo examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short‐term surgical complications requiring a return to the operating room and 30‐day mortality utilizing data from the Multi‐Institutional Study on Tracheotomy (MIST). MethodsA retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. ResultsAmong the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m²) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%–75%]: 11.0 days [7–17 days] versus 9.0 days [5–14 days];p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%–75%]: 10.0 days [6–15 days] versus 10.0 days [6–15 days];p = 0.36). ConclusionBMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. Level of Evidence3Laryngoscope, 134:4674–4681, 2024 

ABSTRACT Patients with vocal cord polyps commonly present with symptoms of hoarseness. Although rare, large polyps can cause shortness of breath and stridor and should be included in the differential for patients with airway obstruction. Dysphonia or hoarseness can be a symptom of underlying disease, such as head and neck cancer. This case illustrates the importance of prompt and accurate diagnosis in a patient with persistent symptoms and a history of smoking. Obtaining a laryngoscopy is crucial to appropriately evaluate the larynx. Proper visualization of the laryngeal structures will help direct patient care toward further diagnostic imaging and medical or surgical intervention if indicated. 

Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare. 

Abstract A major technical hurdle for T cell immune profiling is the time and cost to accurately genotype the Human Leukocyte Antigen (HLA) loci from peripheral blood. Here, we developed a rapid, highly multiplexed approach for HLA typing using RNA from <100,000 peripheral blood mononuclear cells with the Oxford Nanopore Technology (ONT) Minion sequencer. This method uses selective reverse transcription of mRNA of six HLA loci (A,B,C, DRB1, DQB1, DPB1), followed by PCR amplification. The individual amplified HLA cDNA was multiplexed in a single sequencing pool using primers with unique molecular identifiers, designed to permit sequencing errors for enhanced data capture. Pooled HLA amplicons were sequenced using the ONT Minion MK1B and R10.4 flowcells, with sequence Q scores> 20. Total RNA was extracted from PBMC samples from 12 individuals, reverse transcribed and amplified using the designed HLA loci specific primers. The pooled, amplified cDNA was then sequenced for 16 hours on the ONT Minion sequencer. The resulting sequencing data was analyzed and an average depth of coverage of 6000x was observed per sample. An average per loci depth of coverage of 1000x was observed. This method is designed to permit rapid (<24h), low-cost, portable HLA sequencing for T cell immune monitoring and epitope identification for immunologic studies. Arizona Piper Foundation 

Abstract The ability to accurately identify peptide ligands for a given major histocompatibility complex class I (MHC-I) molecule has immense value for targeted anticancer therapeutics. However, the highly polymorphic nature of the MHC-I protein makes universal prediction of peptide ligands challenging due to lack of experimental data describing most MHC-I variants. To address this challenge, we have developed a deep convolutional neural network, HLA-Inception, capable of predicting MHC-I peptide binding motifs using electrostatic properties of the MHC-I binding pocket. By approaching this immunological issue using molecular biophysics, we measure the impact of sidechain arrangement and topology on peptide binding, feature not captured by sequence-based MHC-I prediction methods. Through a combination of molecular modeling and simulation, 5821 MHC-I alleles were modeled, providing extensive coverage across human populations. Predicted peptide binding motifs fell into distinct clusters, each defined with different degrees of submotif heterogeneity. Peptide binding scores generated by HLA-Inception are strongly correlated with quantitative MHC-I binding data, indicating predicted peptides can be ranked, both within and between alleles. HLA-inception also showed high precision when predicting naturally presented peptides and can be used for rapid proteome-scale MHC-I peptide binding predictions. Finally, we show that the binding pocket diversity measured by HLA inception predicts response to checkpoint blockade. Citation Format: Eric A. Wilson, John Kevin Cava, Diego Chowell, Abhishek Singharoy, Karen S. Anderson. Protein structure-based modeling to improve MHC class I epitope predictions. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5376. 

Abstract Introduction: To counteract the rapidly increasing incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), development of effective biomarkers and other novel screening strategies are necessary to effectively detect early disease in well-defined high-risk populations. The most promising biomarkers are circulating tumor HPV DNA (ctHPV), antibodies (Abs) to HPV16 early (E) antigens, and persistent infection with oral oncogenic HPV. Here, we report the prevalence of ctHPV in a population of middle-aged men, a group with high OPC incidence, and evaluate concordance between the three HPV biomarkers. Materials and Methods: We included participants enrolled in the HPV-related Oropharyngeal and Uncommon Cancers Screening Trial of Men (HOUSTON) study between April 2017 and December 2019. The HOUSTON study was designed to evaluate biomarkers and novel screening strategies for HPV-related cancers among middle-aged men (50-64 years), the group with the highest incidence of HPV-related OPC. We tested plasma for ctHPV using a digital droplet polymerase chain reaction (ddPCR) assay (NavDx, Naveris, Waltham, MA). We previously tested the plasma from these participants for HPV16 E Abs using a novel RAPID ELISA and for prevalent oral HPV16 (oHPV16) infection in oral rinse using the cobas HPV Test (Roche Diagnostics, Indianapolis, IN). We used Fisher’s exact test to determine statistical significance for the association between biomarkers (alpha < 0.05). Results: Of 345 samples tested, 343 were adequate for ctHPV analysis. Of these, 314 were negative (92.4%) and two were positive (0.6%; both for HPV16). Twenty-four had an indeterminate (Ind) result (7.0%), meaning ctHPV levels fell outside the established parameters for a negative or positive results. All three markers were available for 340 samples with the following results: ctHPV+/Ab+/oHPV16+: 1 (0.3%); ctHPV+/Ab-/oHPV16-: 1 (0.3%); ctHPV Ind/Ab-/oHPV16+: 3 (0.9%); ctHPV Ind/Ab-/oHPV16-: 21 (6.2%); ctHPV-/Ab+/oHPV16+: 1 (0.3%); ctHPV-/Ab+/oHPV16-: 3 (0.9%); ctHPV-/Ab-/oHPV16+: 16 (4.7%); ctHPV-/Ab-/oHPV16-: 294 (86.5%); all other combinations had no observations. ctHPV was associated with HPV16 E Abs and oHPV16 status individually and combined (individually, p = 0.032 for both and combined, p = 0.025). A ctHPV-/Ab+/oHPV16-man was diagnosed with an anal low-grade squamous intraepithelial lesion and was persistently high-risk HPV-positive at the right tonsil/base of tongue. One man was positive for all three markers and was subsequently diagnosed with stage II (T1N1) HPV16-positive/Epstein-Barr-negative nasopharyngeal cancer four months following study enrollment. Conclusions: ctHPV was rare in a general population of middle-aged men. Our results suggest that these markers in combination may be able to correctly identify early HPV-related cancers. Larger studies are needed to confirm this finding. The authors accept sole responsibility for the statements in this abstract. Citation Format: Kristina R. Dahlstrom, Karen S. Anderson, Erich M. Sturgis. Biomarkers for early diagnosis of human papillomavirus-related oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-037.