Yin, Linda X.

AbstractIntroductionSeveral diagnostic modalities with various sensitivity and specificities can be used to evaluate a parotid mass. The aims of this project were to compare the diagnostic actionability, accuracy, and ability to accurately predict extent of surgery for FNA and frozen section during the evaluation of a parotid mass.MethodsA retrospective chart review of patients who underwent parotidectomy for a parotid mass from January 1, 2015 to January 30, 2022 was conducted. Actionability was defined as a pathology diagnosis or the histologic grade of a lesion, as this provided clear and useful information for the surgeon to act upon. Diagnostic accuracy was determined by comparing FNA and frozen section results to final pathology. Accuracy of extent of surgery was determined by comparing predicted extent of surgery from the FNA or frozen section result to the extent of surgery predicted by the final pathology.ResultsA total of 626 patients were included in this study. FNA was obtained in 396 (63%) patients, while all neoplasms were evaluated by frozen section analysis. FNA diagnosis was actionable in 318 (80%), while frozen section diagnosis was actionable in 616 (98%) patients. Exactly 294 (92.5%) FNA diagnoses were accurate compared with 600 (98%) frozen section diagnoses. The FNA diagnosis predicted appropriate extent of surgery in 294 (74%) while the frozen section diagnosis predicted appropriate extent of surgery in 600 (96%). Among the 396 patients with FNA, frozen section was significantly more likely to accurately predict appropriate extent of surgery compared with FNA (p < 0.001).ConclusionFrozen section is more likely to yield actionable and accurate results compared with FNA. Additionally, frozen section is better than FNA in predicting the appropriate extent of surgery.

ObjectivesMany summer research programs (SRPs) for URiM students exist; however, only a few have been established by otolaryngology programs, who have a unique opportunity to provide a diverse experience. We sought to assess URiM undergraduate student perspectives on the most valuable program features that influence decision‐making and how this might be useful to otolaryngology programs seeking to establish pathway programs.Materials and MethodsAn externally facing REDCap survey composed of 37 questions in scaled, multiple‐choice, and open‐ended form. The survey was delivered to applicants via email over two time periods in April 2021 and February 2022. All survey responses were analyzed using descriptive statistics and categorized according to demographic information, program features, and advertising mechanisms.ResultsSeventy‐one percent of our applicants self‐identified as URiM. Over 60% experienced financial hardship, and 31% experienced educational hardship. The single most important feature when selecting a summer research program (SRP) was access to mentorship followed by clinical shadowing and research opportunities. When program features were aggregated into groups, institutional features were the most important, followed closely by funding features. Finally, students prefer to learn about SRPs through their university, followed by social media, despite many students learning about our program through other means.ConclusionsPaid programs with effective advertising, research, mentoring, and clinical shadowing are highly valued by URiM undergraduate students. Understanding student perspectives is critical for programs aiming to address the “leaky pipeline” while being deliberate in their support of underrepresented students.Level of Evidence5 Laryngoscope, 134:637–644, 2024

AbstractObjectivesOropharyngeal squamous cell carcinoma (OPSCC) has been rising. This manuscript looks to explore racial disparities in the surgical management of OPSCC.MethodsA cancer database was queried for patients with OPSCC diagnosed from 2004 to 2017. Univariate and multivariable logistic regressions were used to evaluate associations between patient race/ethnicity, surgical treatment, and reasons for lack of surgery.Results37 306 (74.3%) patients did not undergo surgery, while 12 901 (25.7%) patients did. Non‐Hispanic black (NHB) patients were less likely to undergo surgery than other races (17.9% vs. 26.5%; p < 0.0001). In clinical discussions, the Asian, Native American, Hawaiian, Pacific Islander (ANAHPI), and unknown race group was more likely to directly refuse surgery when recommended (2.5% vs. 1.5%; p = 0.015).ConclusionRacial differences exist in treatment for OPSCC. NHB patients are less likely to actually undergo surgical management for OPSCC, while other patients are more likely to directly “refuse” surgery outright when offered.

Abstract Background: Recent studies support that high levels of tumor-infiltrating lymphocytes (TILs) were associated with better prognosis in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC). While these studies provide a potential role for TILs as a prognostic biomarker, the analyses were relied on manual quantification performed by pathologists, resulting in inter-observer variability. Deep Learning (DL)-based whole slide hematoxylin and eosin (H&E) image analyses may overcome these challenges. However, this analysis only provides the presence of cell types without consideration for the functional roles of each cell within the tumor immune microenvironment (TME). In this work, we develop a computational pipeline to integrate paired H&E and immunohistochemistry (IHC) images to functionally characterize TILs and investigate their prognostic utility. Methods: We analyzed 88 patients: 42 stage I, 39 stage II, and 7 stage III. Our data contain both H&E and IHCs examining FoxP3, CD3, PD-L1, CD20, etc. on serial sections of the tissue. In-house DL-based H&E analysis used to identify TILs, tumors, and stroma in each tumor, then performed registration between adjacent H&E and IHC images from the same tissue. The patients were then classified into three basic immune phenotypes: immune inflamed (IN; high TILs in the tumor region), immune excluded (EX; TILs are mostly localized in stroma), and immune desert (ID; few/no TILs) based on TIL enrichment in the TME. To functionally characterize TILs, we quantified protein expression from the adjacent IHCs. For example, we further classified each patient into different subtypes based on enriched protein expression (e.g., FoxP3 high IN, FoxP3 low IN). We used the Kaplan-Meier method and multivariate Cox analysis to evaluate the prognostic value of different subtypes enriched with different proteins to predict disease-free survival (DFS). Results: The IN group with 43 patients was significantly associated with good prognosis. Interestingly, further stratification of the IN subgroup based on Foxp3 quantification on TIL regions (i.e., high FoxP3 IN and low FoxP3 IN) showed that high protein expression of FoxP3 in TILs in the IN subgroup is significantly associated with a better prognosis compared to other immune subgroups (HR, 0.16; p-value, 0.003). Multivariate analysis, including other clinical covariates showed that the immune subtypes associated with high FoxP3 are independently associated with DFS. These results demonstrate that DL-based integrative IHC and H&E image analysis could be used to identify subgroups with distinct clinical outcomes. Furthermore, our results reveal unknown roles for Foxp3 expression in the TILs in HPV(+) OPSCC as a prognostic biomarker, a finding which should be evaluated in a larger cohort. Citation Format: Sumanth Reddy Nakkireddy, Inyeop Jang, Minji Kim, Linda X. Yin, Michael Rivera, Joaquin J. Garcia MD, Kathleen R. Bartemes, David M. Routman, Eric J. Moore, Daniel J. Ma, Kathryn M. Van Abel, Tae Hyun Hwang. Integrative spatial analysis of paired IHC and H&E images identifies Foxp3 enriched tumor-infiltrating lymphocytes associated with disease-free survival in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma. [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 4638.

AbstractObjectiveOtolaryngology residency is highly competitive, and applicant academic metrics are scrutinized. The predictive value of preresidency academic metrics on applicants’ future research productivity and career aspirations remains largely undefined.Study DesignRetrospective cohort studySettingAcademic otolaryngology department, 2014 to 2015.MethodsApplicant demographics, publication history, and United States Medical Licensing Examination (USMLE) scores were downloaded from Electronic Residency Application Service archives. Publications during residency were tallied from all PubMed articles indexed between July 1, 2015 and June 30, 2020. Postresidency career paths were examined by 2 investigators (D.J.C. and L.X.Y.) using Google searches with an emphasis on program websites, Doximity, and LinkedIn profiles. Associations with publication potential and postresidency positions were evaluated with Spearman rank correlation coefficients and Kruskal‐Wallis, Wilcoxon rank sum, and χ2 tests.ResultsOf 321 applicants, 226 (70%) matched, and 205 (64%) completed residency by June 2020. Matched residents published a median of 4 (range: 0‐41) manuscripts during residency. USMLE scores, Alpha Omega Alpha status, and the number of preresidency publications did not significantly correlate with publication potential during residency. The number of research experiences had a significant positive correlation with publications during residency (p < 0.001). Asian race (p = 0.002) and geographical region of residency (p < 0.001) also had significant associations with publication potential. Of the 205 graduates, 118 (58%) enrolled in fellowship. Age and female sex (74% vs 48%; p = 0.002) were the only factors significantly associated with pursuing a fellowship.ConclusionIn otolaryngology, not all preresidency academic metrics are associated with publication potential during residency or propensity for fellowship training. Programs should not use academic metrics alone to predict an applicant's future research productivity or career trajectory.

AbstractObjectiveWe aim to explore the prognostic value of tumor‐infiltrating lymphocytes (TILs) in the primary tumor and metastatic lymph nodes of patients with HPV(+)OPSCC. We hypothesize that TILS density at both sites is associated with disease‐free survival in HPV(+)OPSCC.Study DesignMatched case‐control study among HPV(+)OPSCC patients who underwent intent‐to‐cure surgery. Cases developed locoregional or distant recurrence. Controls were matched based on age, sex, pathologic T, N, and overall stage, year of surgery, type of adjuvant treatment received, and the Adult Comorbidity Evaluation‐27 (ACE‐27) score.SettingSingle tertiary care center, May 2007 to December 2016.MethodsTumoral TILs (tTILs) density was defined as % TILs; stromal TILs (sTILs) density was defined as absent/sparse or moderate/dense crowding. Associations between TILs and time to disease progression were assessed using Cox regression models.ResultsForty‐four case‐control pairs (N = 88) were included: 42 (48%) AJCC pStage I, 39 (44%) pStage II, and 7 (8%) pStage III. tTILs density ≥10% (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.17‐0.99, p = .048) and a moderate/dense sTILs density (HR 0.21, 95% CI 0.06‐0.75, p = .016) in the primary tumor were significantly associated with decreased risk of progression. TILs density in the lymph node was associated with decreased risk of progression but did not reach statistical significance. The tTILs and sTILs density correlated strongly between the primary tumor and lymph node. Concordance between the pathologists' was moderate (60%‐70%).ConclusionsIn HPV(+)OPSCC, a higher density of tumoral and stromal TILs in the primary tumor and possibly the lymph node may predict a lower risk of disease progression.

AbstractBackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC).MethodsRetrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC.ResultsAll 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post‐RT (N = 141): 0.68 (0.35) and long‐term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04).ConclusionsLower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.Level of Evidence3

ObjectiveFailure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.MethodsRetrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.ResultsOf 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.ConclusionsDelays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.Level of Evidence4 Laryngoscope, 133:1394–1401, 2023

Introduction Coronavirus disease 2019 accelerated the use of virtual visits within health care. We examined the utility of telemedicine for conducting visits in a tertiary head and neck practice. Methods A retrospective study was conducted on patients presenting via video to a tertiary-level head and neck clinic between January 2020 and December 2020. Patient demographics were collected in addition to visit indication, diagnostic imaging/tests at the time of visit, and post-visit plan. Visits were deemed successful if evaluation by video was sufficient in determining a clinical plan and did not require deferment of recommendations for subsequent in-person consult visits and/or work-up (labs, imaging). Logistic regression was performed to identify variables that served as significant predictors of successful video visits. Results A total of 124 video visits were reviewed. Video visits were successful for the initial evaluation 88.7% of the time ( n = 110). Computerized tomographic scans were the most available diagnostic test, available for 54% of patients ( n = 67), followed by biopsy report 30.6% ( n = 38). Visit indication had a statistically significant effect on whether a treatment plan could be made ( p = 0.024). For new patients with parotid masses ( n = 42), definitive treatment plans could be made 97.6% of the time ( n = 41). Patients presenting with an indication of thyroid mass (odds ratio: 0.19 (confidence interval: 0.00072–0.50), p = 0.018) and other neck mass (odds ratio: 0.035 (confidence interval: 0.0014, 0.90), p = 0.043) were at significantly lesser odds than parotid patients to have a successful video visit. Discussion In this study, virtual visits were successful for a high percentage of head and neck visits, particularly among patients seeking evaluation for parotid-related concerns.