Albert Yoon-Kyu Han

Introduction: Site‐specific identification of human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinoma (HPV+ OPSCC) remains a major diagnostic challenge. We developed a site‐directed mucosal swab assay designed to detect and quantify tumor‐derived HPV DNA shed into the oropharyngeal surface overlying HPV‐associated tumors. Methods: Patients with biopsy‐proven HPV+ OPSCC or oral cavity SCC as controls were enrolled after providing informed consent. Swabs of the tumor site as well as the contralateral normal mucosa were collected. Swab‐derived DNA was extracted and analyzed by quantitative PCR targeting HPV16 and HPV genotyping with Sanger sequencing. Multivariable linear regression models were used to evaluate associations between swab‐based viral load and clinicopathologic features. Results: In a prospective cohort of 30 patients with HPV+ OPSCC, tumor‐side swabs detected HPV DNA in 30 of 30 cases. Swabs obtained from the contralateral mucosa showed substantially lower HPV DNA levels, demonstrating strong spatial specificity for the tumor‐bearing region. The assay limit of detection was determined to be ~10 HPV16 copies per reaction (1 viral genome per 500 diploid cells). All negative control patients with oral cavity SCC had negative results. Regression models revealed node‐positive status to be independently associated with low quantitative HPV16 viral load (fold change = 0.013, 95% CI: 0.001–0.178). Conclusions: By enabling minimally invasive, anatomically targeted detection of HPV‐driven cancer at the primary site, this swab‐based assay has the potential to shorten the diagnostic pathway for HPV+ OPSCC while providing quantitative viral load measurements that may serve as a surrogate biomarker for intratumoral biology in HPV+ OPSCC.

Objective: Despite improved survival for patients with HPV‐associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC), up to 30% of cancers recur. This study elucidates independent predictors of recurrence and survival in HPV+ OPSCC patients. Study design: Retrospective cohort study. Setting: Academic tertiary care center. Methods: Patients diagnosed with HPV+OPSCC from 2014 to 2024 were included. Electronic health records were manually searched for demographic, oncologic, treatment, and outcomes data. The primary outcome was recurrence within 5‐years of completion of primary treatment. The secondary outcome was 5‐year survival. Kaplan‐Meier and log‐rank tests were performed for univariate analyses. Cox regression analysis identified independent predictors of recurrence and mortality. Results: Of the 239 patients included, 61 (25.5%) experienced recurrence within 5 years after completion of definitive treatment. Of recurrent cases, over one‐third involved distant metastases, predominantly to the lung, with a subset involving atypical sites such as bone, liver, and skull base. On multivariable Cox regression analysis, perineural invasion was independently associated with any recurrence (HR: 2.440, 95% CI: 1.330, 4.477) and distant metastatic recurrence (HR: 3.107, 95% CI: 1.097, 8.794). The overlapping oropharynx tumor subsite was significantly associated with mortality (HR: 2.102, 95% CI: 1.053, 4.198). Conclusion: Our results highlight distinct patterns of recurrence and survival which support the consideration of more individualized surveillance approaches, especially in HPV+ OPSCC patients with perineural invasion.

Objectives Cervical chordoma is a rare, low-grade primary bone tumor occurring in the axial skeleton. Due to challenges in surgical exposure caused by anatomic location, patients may experience dysfunction in speech and swallowing. The objective of this study was to characterize speech and swallowing outcomes for patients undergoing surgical resection of cervical chordoma. Moreover, we detail in-depth two cases with similar initial presentations to compare prognostic factors and management strategies. Methods Eleven patients with histologically confirmed cervical chordoma treated between 1993 and 2020 were included in this retrospective case series. Outcomes measured included overall survival, disease-free survival, need for enteral feeds, as well as results of modified barium swallow study (MBSS) and fiberoptic laryngoscopy. Results The mean age at diagnosis was 55.9 years. The patient population was 81.8% male. Mean survival after diagnosis was 96 months. Four (36.4%) patients required post-operative MBSS and demonstrated aspiration. All four of these patients presented with tumors in the superior cervical spine and received surgeries utilizing anterior approaches. Of the four, 2 required enteral feeds long-term. Four (36.4%) patients endorsed dysphonia. One patient developed post-operative right vocal fold paresis. The remaining three patients experienced stable dysphonia pre- and post-operatively. Additionally, three (27%) patients required tracheostomy placement, two of which remained in place long-term. Conclusions Dysphagia is a common side effect of cervical chordoma resection. It is associated with the use of an anterior approach during resection and with tumors located in the superior cervical spine. Patients with postoperative dysphagia should receive early multidisciplinary swallow rehabilitation. Level of Evidence 4 Laryngoscope, 2024

Complete surgical resection of the tumor for Head and neck squamous cell carcinoma (HNSCC) remains challenging, given the devastating side effects of aggressive surgery and the anatomic proximity to vital structures. To address the clinical challenges, we introduce a wide-field, label-free imaging tool that can assist surgeons delineate tumor margins real-time. We assume that autofluorescence lifetime is a natural indicator of the health level of tissues, and ratio-metric measurement of the emission-decay state to the emission-peak state of excited fluorophores will enable rapid lifetime mapping of tissues. Here, we describe the principle, instrumentation, characterization of the imager and the intraoperative imaging of resected tissues from 13 patients undergoing head and neck cancer resection. 20 x 20 mm2 imaging takes 2 second/frame with a working distance of 50 mm, and characterization shows that the spatial resolution reached 70 {\mu}m and the least distinguishable fluorescence lifetime difference is 0.14 ns. Tissue imaging and Hematoxylin-Eosin stain slides comparison reveals its capability of delineating cancerous boundaries with submillimeter accuracy and a sensitivity of 91.86% and specificity of 84.38%.

Sinonasal cancer is a heterogeneous orphan disease of diverse histologies, each with distinct clinical, oncologic, and toxicity profiles. Because of the comparative rarity of these cancers, sinonasal cancers are treated as a grouped diagnosis despite their clinical and biological heterogeneity. Multimodality treatment with a combination of surgery, chemotherapy, and/or radiotherapy is the standard‐of‐care for advanced‐stage patients but there are few surveillance or follow‐up practice guidelines or formalized survivorship care pathways. A scoping literature review was conducted via PubMed, EMBASE, and Google Scholar. A total of 112 studies were included, which were grouped along the following topics: surveillance, second primary tumors, quality of life, and symptom burden. Sinonasal cancer tends to exhibit a higher rate of local failure and occur in a delayed fashion compared to mucosal malignancies of the head and neck. Moreover, the site of failure and time‐varying risk of recurrence is histology‐specific. Following multimodality treatment of the skull base, patients may experience endocrine, visual, auditory, sinonasal, olfactory, and neurocognitive deficits, as well as psychosocial impairments that impact multiple physical and neuropsychological domains, resulting in diminished quality of life. Sinonasal cancer patients would benefit from tailored, histology‐specific survivorship programs to address the recurrence, second primary, and functional impairments resulting from disease and treatment toxicity.

Objectives: To examine the epidemiology, subtypes, trends over time, and predictive factors for recurrence and malignant transformation of sinonasal papillomas. Methods: A retrospective chart review of 118 patients with sinonasal papillomas from 2009 to 2019 was conducted at the University of California, Los Angeles. This study is a follow-up to a previously published study from 2000 to 2009 at the same academic center. Results: The mean age was at presentation was 58.5 years, with a 2:1 male to female ratio, and average follow-up of 30.1 months. The rate of recurrence after complete resection was 19% with an average of 32.6 months to recurrence. The time to recurrence followed a bimodal distribution with 57% of cases recurring within 24 months (mean = 10) and 43% from 40 to 103 months (mean = 61). The proportion of the inverted papillomas rose from 38% in 2000-2004 to 89.6% in 2015-2019. Patients presenting at a younger age had a higher chance of recurrence (mean age 52 with recurrence vs. 61 without recurrence). Age did not correlate with histopathologic transformation in surgical pathology. Furthermore, histopathological transformation did not raise the chance of recurrence. Smoking, alcohol use, chronic rhinosinusitis, and allergic rhinitis were not associated with any of the outcome measures in this study. The most significant factor predicting recurrence, beside age at presentation, was the history of two or more prior sinus surgeries for papillomas or other reasons (OR = 3.52 and 5.81). Conclusion: This study explored the features of sinonasal papillomas as well as the risk factors for recurrence and transformation. Younger age at presentation and two or more prior surgeries for papillomas were associated with recurrence. Time to recurrence followed a bimodal distribution, with late recurrences happenning from 40 to 103 months after surgery, emphasizing the importance of long-term follow-up for timely resection of tumors and prevention of malignancy.

Objectives: 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.Methods: 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.Results: 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).Conclusions: 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.Level of Evidence: 4 Laryngoscope, 133:437–442, 2023

Secondary syphilis rarely affects the head and neck including the oropharynx and cervical lymph nodes. These patients present with throat pain, cystic/necrotic lymphadenopathy, and mucosal swelling. Sometimes this constellation of symptoms can be mistaken for head and neck cancer. We report a case of an enlarging throat and painless cystic neck mass in a transgender woman in her forties who was initially suspected to have oropharyngeal squamous cell carcinoma. A subsequent workup revealed the presence of spirochetes without cellular atypia consistent with secondary syphilis. We include the ultrasonography images as well as an endoscopic photograph of the oropharyngeal manifestation in this report.

Intractable hiccups are a rare yet debilitating pathology with a broad differential and often indicate a more serious underlying pathology, which can range from neoplasms to structural abnormalities. In this case report, we present a 64-year-old male with seven months of intractable hiccups determined to be caused by eventration of the right hemidiaphragm. The patient was treated with baclofen to treat the hiccups pharmacologically. He was also prescribed voice therapy to establish rescue breathing techniques and reduce laryngospasm. Finally, he was referred to thoracic surgery for further evaluation and potential surgical intervention should his diaphragmatic eventration worsen or cause hypoxemia. To our knowledge, this is the first reported case of an association between diaphragmatic eventration and intractable hiccups. It is important to highlight this addition to the broad differential of intractable hiccups and to emphasize an interdisciplinary approach to workup and treatment of intractable hiccups.

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 < .001). Although increasing hospital volume did not alter the odds of mortality, patients treated at high‐volume centers were less likely to experience both surgical (adjusted odds ratio [AOR] 0.81, 95% confidence interval [CI] 0.67–0.97, P = .025) and medical complications (AOR 0.70, 95% CI 0.57–0.85, P < .001). Furthermore, these patients had shorter hospitalizations (−2.1 days, 95% CI −2.7 to −1.4 days, P < .001) and decreased costs (−$8,100, 95% CI −11,400 to −4,700, P < .001) compared to counterparts at low‐volume centers. However, hospital volume did not impact 90‐day readmissions.Conclusion: Patients undergoing HNCA resection with flap reconstruction at high‐volume centers were less likely to experience surgical and medical complications while incurring shorter hospitalizations and lower costs. Implementation of volume standards may be appropriate to improve outcomes in this surgical population.Level of Evidence: 3 Laryngoscope, 132:1381–1387, 2022