Reconstruction of Palatal Defects Using a Composite Chondromucosal Nasoseptal Flap and Comparative Analysis.

OBJECTIVE: The use of composite chondromucosal nasal septal flaps (ccNSF) has been demonstrated to be effective in cadaveric studies for the anterior skull base and the orbit. However, their application in the clinical setting remains unexplored. Our study aims to introduce a new method for treating palatal defects using ccNSF. Additionally, we studied the average NSF area and compared it to the average palate area. METHODS: We collected 108 CT scans from the medical records of patients without head and neck pathologies from a tertiary medical institution. We quantified the quadrangular (septal) cartilage and palate areas. Furthermore, we included a clinical case in which we used the ccNSF for the palatal defect reconstruction. This was to compare the mean area between the palate and the septal cartilage. RESULTS: The ccNSF covered the palatal defect without any significant complications for the first 9 months of follow-up. A total of 102 CT scans met the inclusion criteria and were measured. We found that the mean quadrangular cartilage had a length of 2.50 (±0.52) cm, a width of 2.28 (±0.51) cm, and an area of 5.43 (±1.68) cm2. The mean palate length was 2.73 (±0.44) cm, with a width of 3.13 (±0.34) cm, and area of 7.87 (±1.43) cm2. CONCLUSIONS: The ccNSF proved successful in palatal defect reconstruction, resulting in positive outcomes and no major complications until the 9-month follow-up. The ccNSF is a useful flap that avoids the use of free flap transfer and its associated morbidities. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Creating an Undergraduate Research Program in Otolaryngology-Head and Neck Surgery (Oto-HNS) for Students Underrepresented in Medicine.

Objectives: To report implementation and outcomes associated with a novel paid Summer Undergraduate Research Education Program (SREP) over the first 2 years in an academic otolaryngology program recruiting students underrepresented in medicine (URiM). Methods: A 10-week program including a research bootcamp, curriculum, mentoring, and clinical shadowing was created. Grant funding to provide salary and support for transportation, conference attendance, and graduate school preparation or applications was procured. Primary objectives included (1) development of successful mentorship relationships; (2) increasing student-reported outcomes using pre- and post-program surveys to assess confidence, career planning, and overall satisfaction; (3) increasing exposure to medicine; (4) completion of an oral presentation; and (5) submission of a manuscript. Secondary objectives included abstract submission and completion of a graduate exam course or graduate school applications. Tertiary objectives included conference attendance and graduate school matriculation. Results: One hundred thirty-five total applications were reviewed (89 from year 1 and 46 from year 2). Twelve students were interviewed for 3 spots in year 1, while 11 students were interviewed for 6 spots in year 2 (median application score, 9.25 (range, 1-14); median interview score, 8.7 (range, 5.4-10); acceptance rate, 6.7% (9/135)). Students met all primary objectives. Mean program survey scores increased from 3.8 to 4.77 (p < 0.0001). Eight of nine students submitted an abstract to a national conference, with five of eight students accepted for a presentation. Two students were accepted into graduate school, while five others are on track for graduate school application. Conclusion: Identifying mentors, curriculum, and opportunities to meaningfully strengthen graduate school applications for URiM students through a clinically rigorous, financially supported, and research-focused summer program in an academic otolaryngology program is feasible and may be an effective means of increasing diversity in medicine and otolaryngology. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02021-z.

Addressing positive multi-cancer early detection tests in head and neck Surgery: Experience with head and neck work up for high-risk referrals.

OBJECTIVES: Blood-based multi-cancer early detection (MCED) tests are now commercially available. However, there are currently no consensus guidelines available for head and neck cancer (HNC) providers to direct work up or surveillance for patients with a positive MCED test. We seek to describe cases of patients with positive MCED tests suggesting HNC and provide insights for their evaluation. METHODS: Retrospective chart review of patients referred to Otolaryngology with an MCED result suggesting HNC. Patients enrolled in prospective MCED clinical trials were excluded. Cancer diagnoses were confirmed via frozen-section pathology. RESULTS: Five patients were included (mean age: 69.2 years, range 50-87; 4 male) with MCED-identified-high-risk for HNC or lymphoma. Only patient was symptomatic. After physical exam and follow-up head and neck imaging, circulating tumor HPV DNA testing, two patients were diagnosed with p16 + oropharyngeal squamous cell carcinomas and underwent appropriate therapy. A third patient had no evidence of head and neck cancer but was diagnosed with sarcoma of the thigh. The remaining two patients had no evidence of malignancy after in-depth workup. CONCLUSIONS: In this retrospective study, 2 of 5 patients referred to Otolaryngology with a positive MCED result were diagnosed with HPV + oropharyngeal squamous cell carcinoma. We recommend that positive HNC MCED work up include thorough head and neck examination with flexible laryngoscopy and focused CT or MRI imaging. Given the potential for inaccurate MCED tissue of origin classification, PET/CT may be useful in specific situations. For a patient with no cancer identified, development of clear guidelines is warranted.

Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial.

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).

Association Between Social Determinants of Health, Distance from Treatment Center, and Treatment Type with Outcomes in Human Papillomavirus Associated Oropharyngeal cancer.

OBJECTIVES: Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN: Retrospective review. METHODS: HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS: 874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS: Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.

Partial superficial parotidectomy for pleomorphic adenoma of the parotid gland: Early post-operative outcomes.

INTRODUCTION: There has been historical controversy regarding the extent of resection in the management of pleomorphic adenomas. This study aims to evaluate the extent of surgery and short-term postoperative outcomes of partial superficial parotidectomy (PSP) for the management of pleomorphic adenomas at a tertiary, high-volume center. METHODS: A retrospective chart review of patients who underwent PSP was performed. Variables included demographics, pre-operative facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. RESULTS: 151 adults who underwent PSP for pleomorphic adenoma from January 1st, 2000 to December 31st, 2022 were identified. Median age was 55 (IQR 40-66) years with females representing 74 % of the cohort. Median tumor size at presentation was 1.8 (IQR 1.3-2.3) cm. Baseline facial nerve function was excellent for most patients (House-Brackmann I, 99 %). Most patients underwent a superficial inferior parotidectomy (88 %). Modified Blair incision (70 %) was the most common incision. Intraoperatively, the facial nerve was identified in 149 (99 %) patients. The main trunk was identified in 126 (85 %) patients. No patient had tumor spillage. Only two patients required parotid bed reconstruction. The most common complication was ear numbness (60 %). Postoperatively, 114 patients were House-Brackmann grade I at both preoperative and postoperative assessment, 8 went from grade I to II, and 1 went from grade VI to II (Bell's palsy that resolved to grade II following surgery). Median follow-up was 1(IQR 1-5) month. CONCLUSION: PSP is efficacious in the management of pleomorphic adenomas with preservation of facial nerve function, and minimal post-operative complications. Future study is needed to assess long term recurrence risk.

Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group.

OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.

Association of sarcopenia with oncologic outcomes of primary treatment among patients with oral cavity cancer: A systematic review and meta-analysis.

GOAL: We performed a systematic review of the literature and meta-analysis to determine how radiographic sarcopenia assessment methods and the presence of pre-treatment sarcopenia impact oncologic outcomes in patients with oral cavity cancer. INTRODUCTION: Pre-treatment sarcopenia has been associated with poor outcomes in many different malignancies, including head and neck cancers. However, the impact sarcopenia has on outcomes for oral cavity cancer patients is not well understood. RESULTS: Twelve studies met our inclusion criteria, totaling 1007 patients. 359 (36%) of these patients were reported as sarcopenic. The most commonly utilized sarcopenia assessment methods were L3 skeletal muscle index (n = 5) and C3 skeletal muscle index to estimate L3 skeletal muscle index (n = 5). The majority of studies established their sarcopenia cutoffs as the lowest quartile skeletal muscle index in their patient cohorts. Five studies were included in our meta-analysis, totaling 251 sarcopenic and 537 non-sarcopenic patients. Compared to non-sarcopenic patients, sarcopenic patients were found to have significantly poorer overall survival (univariate: HR = 2.24, 95% CI: 1.71-2.93, I2 = 0%; multivariate: HR = 1.93, 95% CI: 1.47-2.52, I2 = 0%) and disease-free survival (univariate: HR = 2.10, 95% CI: 1.50-2.92, I2 = 0%; multivariate: HR = 1.79, 95% CI: 1.29-2.47, I2 = 10%). CONCLUSIONS: Over one-third of oral cavity cancer patients may present with sarcopenia. Pre-treatment sarcopenia is associated with significantly worse overall and disease-free survival.

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center.

OBJECTIVES: To investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). MATERIALS AND METHODS: Retrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. RESULTS: A total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2-87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6-2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). CONCLUSION: There is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Selective Deep Lobe Parotidectomy vs Total Parotidectomy for Patients With Benign Deep Lobe Parotid Tumors.

Importance: Limited literature exists on surgical outcomes after selective deep lobe parotidectomy (SDLP) with preservation of superficial lobe for patients with benign deep lobe tumors. Objective: To compare the following factors for SDLP vs total parotidectomy for patients with benign tumors in the deep lobe: postoperative complications, including facial nerve paresis or paralysis, Frey syndrome, first bite syndrome, cosmetic defect, sialocele formation, and wound infection; and tumor control and recurrence. Design, Setting, and Participants: This case series included 273 adults who underwent SDLP (n = 177) or total parotidectomy (n = 96) at a single tertiary care institution for benign parotid tumors located in the deep lobe or deep lobe and parapharynx from January 1, 2000, to December 31, 2020. Exposure: Selective deep lobe parotidectomy vs total parotidectomy. Main Outcomes and Measures: Incidence of postoperative complications and tumor recurrence. Results: Among 273 patients (SDLP, 177 [65%]; 122 women [69%]; median age at surgery, 58 years [IQR, 46-67 years]; total parotidectomy, 96 [35%]; 57 women [59%]; median age at surgery, 59 years [IQR, 40-68 years]), the most common tumor was pleomorphic adenoma (SDLP, 128 of 177 [72%]; total parotidectomy, 62 of 96 [65%]). An abdominal dermal fat graft was less commonly performed for patients who underwent SDLP than those who underwent total parotidectomy (2 of 177 [1%] vs 20 of 96 [21%]; difference, -20% [95% CI, -28% to -11%]). The rate of great auricular nerve preservation was higher in the SDLP group than in the total parotidectomy group (84 of 102 [82%] vs 20 of 34 [59%]; difference, 24% [95% CI, 5%-42%]). No meaningful difference in length of hospital stay was found. The percentage of patients with House-Brackmann grade I immediately after surgery was 48% (85 of 177) in the SDLP group and 21% (20 of 96) in the total parotidectomy group (difference, 28% [95% CI, 16%-40%]). There were no clinically meaningful differences in rates of hematoma, sialocele, seroma, ear numbness, wound infection, or unplanned return to emergency department or operating room. The SDLP group reported a lower rate of Frey syndrome than the total parotidectomy group (1 of 137 [1%] vs 12 of 78 [15%]; difference, -15% [95% CI, -23% to -7%]), as well as a lower rate of facial contour defect (28 of 162 [17%] vs 25 of 84 [30%]; difference, -13% [95% CI, -24% to -1%]) and a higher rate of first bite syndrome (34 of 148 [23%] vs 7 of 78 [9%]; difference, 14% [95% CI, 5%-23%]). The percentage of patients with House-Brackmann grade I at their first follow-up visit was 67% (118 of 177) in the SDLP group compared with 49% (47 of 96) in the total parotidectomy group (difference, 17% [95% CI, 4%-30%]). There was no clinically meaningful difference in House-Brackmann grade after 1 year. Conclusions and Relevance: Findings of this case series study suggest that SDLP can be considered an effective and even superior technique for management of benign tumors in the deep parotid lobe. Advantages associated with SDLP include reduction in need for reconstruction for facial contour defect and reduction in complications, such as immediate facial nerve weakness and Frey syndrome. The incidence of first bite syndrome was higher in the SDLP group. Tumor control was not compromised by SLDP.

Ability for fine needle aspiration and frozen section to predict extent of parotidectomy.

INTRODUCTION: Several 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. METHODS: A 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. RESULTS: A 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). CONCLUSION: Frozen 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.

Racial disparities in surgical treatment of oropharyngeal cancer: A Surveillance, Epidemiology, and End Results review.

OBJECTIVES: Oropharyngeal squamous cell carcinoma (OPSCC) has been rising. This manuscript looks to explore racial disparities in the surgical management of OPSCC. METHODS: A 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. RESULTS: 37 306 (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). CONCLUSION: Racial 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.

Safety outcomes and patient convenience in outpatient parotidectomy.

BACKGROUND: Parotidectomies have historically been performed on an inpatient basis despite being well-tolerated surgeries with minimal postoperative wound care and low rates of complications at high-volume institutions. Past studies have supported the safety of outpatient surgery for parotidectomy but have been limited to superficial parotidectomy and have not addressed the patient experience surrounding the surgical intervention such as pre-operative and post-operative care and communication. PURPOSE: This study assesses the impact of outpatient superficial, deep, and partial parotid surgery on various parameters including surgical safety, distance traveled for care, utilization of telehealth, and patient-initiated communication. MATERIALS AND METHODS: Retrospective study from January 2020 to October 2021. Patients undergoing superficial lobe, deep lobe, and partial parotidectomies for benign and malignant pathologies were divided into inpatient and outpatient cohorts. A multivariable model examined the relationship between admission status and surgical complications, adjusted for age, sex, and tumor size. RESULTS: 159 patients total, 94 outpatient and 65 inpatients. No statistical difference in rates of surgical complications with the exception of salivary leak. There was an increased rate of salivary leak reported in the inpatient group (OR 5.4, 95 % CI 1.6 to 18.0, p = 0.01). Mean patient travel distance of 354 miles one-way. Post-operatively, 76 % were evaluated via video visit. Following discharge, >55 % of patients initiated communication with the surgical team, which was not statistically different between the groups. CONCLUSIONS: Outpatient parotidectomy is safe and can be more convenient, but telehealth communication must be balanced with rigorous attention to patient education.

Development and Validation of Instrument for Operative Competency Assessment in Selective Neck Dissection.

BACKGROUND: Instruments to assess surgical skills have been validated for several key indicator procedures in otolaryngology. Selective neck dissection is a core procedure for which trainees must integrate knowledge of complex head and neck anatomy with technical surgical skills. An instrument for assessment of surgical performance in selective neck dissection has not been previously developed. The objective of the current study is to develop and validate an instrument for assessing surgical competency for level II-IV selective neck dissection. DESIGN: A Delphi working group comprised of 23 fellowship trained head and neck surgeons from 17 institutions was assembled. The modified Delphi method encompassed a 3-step process, including 2 anonymous voting rounds to successively refine individual items and establish levels of consensus. Thresholds for achieving strong consensus, at >80% agreement, were determined a priori. The resulting instrument was subsequently validated in a prospective cohort of 17 resident surgeons, spanning postgraduate year 1 to 5 training experience. Participants were asked to perform a level II-IV selective neck dissection on fresh-frozen cadaveric specimens. Performance was scored by 2 independent, blinded observers using the devised instrument and construct validity was assessed. RESULTS: Through the modified Delphi process a final list of 30 items, considered to be the most essential items for achieving the goals of a level II-IV selective neck dissection, was developed. Construct validity was supported by a positive association between instrument scores compared to both resident postgraduate year level and number of head and neck rotations completed. CONCLUSION: The development and validation of a novel instrument for assessment of surgical competency in level II-IV selective neck dissection, a key indicator case in otolaryngology, is described. This new instrument may be used to provide objective feedback on overall and task-specific competency to identify surgical deficiencies and offer granular feedback to enhance surgical training.

Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Failure 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. METHODS: Retrospective 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. RESULTS: Of 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. CONCLUSIONS: Delays 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 EVIDENCE: 4 Laryngoscope, 133:1394-1401, 2023.

Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer.

BACKGROUND: We 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). METHODS: Retrospective 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. RESULTS: All 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). CONCLUSIONS: Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.

The Number of Radiographically Positive Lymph Nodes Further Stratifies Patient Survival Among Clinical N1 Patients With Human Papillomavirus-Associated Oropharyngeal Cancer.

Purpose: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) requires further study to optimize the existing clinical staging system and guide treatment selection. We hypothesize that incorporation of the number of radiographically positive lymph nodes will further stratify patients with clinical N1 (cN1) HPV(+)OPSCC. Methods and Materials: A post hoc analysis from 2 prospective clinical trials at a high-volume referral center was conducted. Patients underwent primary tumor resection and lymphadenectomy, followed by either standard-of-care radiation therapy (60 Gy in 30 fractions) with or without cisplatin (40 mg/m2 weekly) or de-escalated radiation therapy (30 Gy in 20 twice-daily fractions) with concomitant 15 mg/m2 docetaxel once weekly. Imaging studies were independently reviewed by a blinded neuroradiologist classifying radiographic extranodal extension (rENE) and the number and maximal size of involved lymph nodes. Patients without pathologic data available for assessment were excluded. Results: A total of 260 patients were included. Of these, 216 (83%) were cN1. Patients had a median of 2 radiographically positive lymph nodes (range, 0-12), and 107 (41%) had rENE. For cN1 patients, stratifying by radiographically positive lymph nodes (1-2 vs 3-4 vs >4) was predictive of progression-free survival (PFS) (P = .017), with 2-year PFS rates of 96%, 88%, and 81%, respectively. More than 2 radiographically positive lymph nodes was identified as a significant threshold for PFS (P = .0055) and overall survival (P = .029). Radiographic ENE and lymph node size were not predictive of PFS among cN1 patients. Conclusions: The number of radiographically positive lymph nodes is predictive of PFS and overall survival and could be used to meaningfully subcategorize cN1 patients with HPV(+)OPSCC. We recommend further validation of our proposal that cN1 patients with 1 to 2 radiologically positive lymph nodes be categorized as cN1a, patients with 3 to 4 radiologically positive lymph nodes categorized as cN1b, and patients with >4 radiographically positive lymph nodes categorized as cN1c.