Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma.

Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.

Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches. METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed. RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration. CONCLUSION: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.

Translocations and Gene Fusions in Sinonasal Malignancies.

PURPOSE OF REVIEW: During the past few years there has been an expansion in our understanding of gene fusions and translocations involved in cancer of the sinonasal tract. Here we review the downstream biologic effects, clinical characteristics, and pathologic features of these tumors. The molecular consequences and neo-antigens resulting from these chromosomal aberrations are considered and targets for current and future clinical trials discussed. RECENT FINDINGS: Several new, clinically relevant, chromosomal aberrations have been discovered and evaluated to varying degrees in sinonasal tumors including DEK::AFF2, BRD4::NUT, ADCK4::NUMBL, and ETV6::NTRK3. Sinonasal malignancies demonstrate a diverse genetic landscape and varying clinical courses. Recent studies illustrate that gene fusions and translocations may play a role in carcinogenesis in certain sinonasal tumor subtypes and may be used to develop new biomarker-driven and patient-centered treatments.

Reconstruction in open anterior skull base surgery: A review and algorithmic approach.

PURPOSE: Defects resulting from open resection of anterior skull base neoplasms are difficult to reconstruct. Our objective was to review the literature and describe an evidence-based algorithm that can guide surgeons reconstructing anterior skull base defects. METHODS: A research librarian designed database search strategies. Two investigators independently reviewed the resulting abstracts and full text articles. Studies on reconstruction after open anterior skull base resection were included. Studies of lateral and posterior skull base reconstruction, endoscopic endonasal surgery, traumatic and congenital reconstruction were excluded. Based on the review, a reconstructive algorithm was proposed. RESULTS: The search strategy identified 603 unique abstracts. 53 articles were included. Adjacent subsites resected, defect size, radiotherapy history, and contraindications to free tissue transfer were identified as key factors influencing decision making and were used to develop the algorithm. Discussion of the reconstructive ladder as it applies to skull base reconstruction and consideration of patient specific factors are reviewed. Patients with a prior history of radiotherapy or with simultaneous resection of multiple anatomic subsites adjacent to the anterior skull base will likely benefit from free tissue transfer. CONCLUSIONS: Reconstruction of anterior skull base defects requires knowledge of the available reconstructive techniques and consideration of defect-specific and patient-specific factors.

Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity.

Although low-grade non-intestinal-type sinonasal adenocarcinoma (SNAC) is formally a diagnosis of exclusion defined by the absence of salivary or intestinal differentiation, most tumors in this category comprise a distinctive histologic group that are increasingly thought to derive from seromucinous glands. However, the molecular underpinnings of SNAC remain poorly understood, and it is unclear if diverse genetic alterations recently reported in isolated cases should delineate separate subgroups. This study aims to perform comprehensive evaluation of gene fusions and mutations and their histologic correlates in low-grade SNAC to clarify its pathogenesis and classification. We identified 18 non-intestinal-type SNAC that all displayed characteristic tubulopapillary architecture and low-grade cytology, although several cases had other unique histologic features and 3 showed intermixed high-grade areas. Among tumors stained with S100 protein, SOX10, and DOG1, 86% expressed at least one of these seromucinous markers. Of 17 cases with sufficient RNA or DNA available for analysis, likely oncogenic molecular alterations were identified in 76% of cases, most notably including CTNNB1 p.S33F mutations in 2 cases, concomitant BRAF p.V600E and AKT1 p.E17K mutations in 2 cases, and ETV6::NTRK3, PRKAR1A::MET, FN1::NRG1, and DNAJB1::PRKACA fusions in 1 case each. While tumors with most genetic alterations were histologically indistinguishable, cases with CTNNB1 mutations had intermixed squamoid morules and cases with BRAF and AKT1 mutations showed a myoepithelial cell population and prominent papillary to micropapillary architecture. Overall, these findings confirm previous reports of frequent seromucinous differentiation in low-grade SNAC. However, these tumors display striking molecular diversity with involvement of multiple kinase fusions, leading to frequent activation of signaling cascades including the MAPK pathway. While most genetic alterations are not associated with sufficiently distinctive histologic features to suggest separate classification, biphasic tumors with BRAF p.V600E mutations are more unique and may represent a distinctive subgroup.

Limited sinonasal Rosai-Dorfman disease presenting as chronic sinusitis.

AIMS: The sinonasal tract is a common extranodal site for Rosai-Dorfman disease (RDD). Recently, histiocytes with features of RDD were identified in the clinical setting of chronic sinusitis. This study evaluates whether this phenomenon should be considered part of the RDD spectrum or classified separately as RDD-like histiocytes. METHODS AND RESULTS: We prospectively collected 13 cases showing histological features of RDD in chronic sinusitis patients and identified 14 with similar findings (3.5%) via retrospective review of 403 sinus contents over 2 years. All 27 cases displayed nodular aggregates of eosinophilic histiocytes with intermixed lymphoplasmacytic inflammation, prominent eosinophils and emperipolesis. The histiocytes were positive for S100 protein and cyclin D1 and negative for CD1a and CD207. All patients presented with severe chronic sinusitis without tumour formation or systemic symptoms. Twelve patients with follow-up (55%) required repeat sinus surgery compared with just 43 other sinusitis patients evaluated (11%); features of RDD were present in their additional specimens. Two cases that underwent targeted next-generation sequencing (20%) had oncogenic mutations in NF1 and KEAP1. CONCLUSIONS: Overall, these findings confirm diagnostic histological and immunohistochemical features of RDD in a subset of chronic sinusitis specimens. While patients uniformly lack systemic involvement or tumefactive growth, they have a high risk of recurrent sinus disease. Although the relatively subtle nature of the findings raises consideration of separate classification, the presence of occasional oncogenic mutations and evidence of consistent MAPK/ERK pathway activation via cyclin D1 positivity suggests that this phenomenon represents a unique limited manifestation of RDD.

Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

A new evaluation of previously published data suggested to us that the accumulation of mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized that normal stem cell division rates might decrease as we age. To test this hypothesis, we evaluated cell division rates in the epithelium of human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant decrease in cell division rates with age. In contrast, cell division rates did not decrease in the colon of aged mice, and only small decreases were observed in their small intestine or esophagus. These results have important implications for understanding the relationship between normal stem cells, aging, and cancer. Moreover, they provide a plausible explanation for the enigmatic age-dependent deceleration in cancer incidence in very old humans but not in mice.

Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction.

OBJECTIVE: The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. METHODS: Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. RESULTS: By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (p < 0.05), while the Apnea-Hypopnea Index (AHI) changed little (p = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all p < 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (p < 0.05), except with the AHI (p > 0.05). CONCLUSION: Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.

The 5-factor modified frailty index predicts health burden following surgery for pituitary adenomas.

PURPOSE: Frailty is known to influence cost-related surgical outcomes in neurosurgery, but quantifying frailty is often challenging. Therefore, we investigated the predictive value of the 5-factor modified frailty index (mFI-5) on total hospital charges, LOS, and 90-day readmission for patients undergoing pituitary surgery. METHODS: The medical records of all patients undergoing endoscopic endonasal resection of pituitary adenomas at an academic medical center between January 2017 and December 2018 were retrospectively reviewed. Bivariate statistical analyses were conducted using Fisher's exact test, chi-square test, and independent samples t-test. Linear and logistic regression models were used for multivariate analysis. RESULTS: Our cohort (n = 234) had a mean age of 53.8 years (standard deviation 14.6 years). Sex distributions were equal, and most patients were Caucasian (59%). On multivariate linear regression, with each one-point increase in mFI-5, total LOS increased by 0.64 days in the overall cohort (p < 0.001), 1.08 days in the Cushing disease cohort (p = 0.045), and 0.59 days in non-functioning tumors cohort (p = 0.004). Total charges increased by $3954 in the whole cohort (p < 0.001), $10,652 in the Cushing disease cohort (p = 0.033), and $2902 in the non-functioning tumors cohort (p = 0.007) with each one-point increase in mFI-5. Greater mFI-5 scores were associated with greater odds of 90-day readmission in both overall and Cushing disease cohorts, but these associations did not reach statistical significance. CONCLUSION: A patient's mFI-5 score is significantly associated with increased length of stay and hospital charges for patients undergoing pituitary surgery. The mFI-5 may hold peri-operative value in patient counseling for pituitary adenoma surgery.

Focused endoscopic endonasal craniocervical junction approach for resection of retro-odontoid lesions: surgical techniques and nuances.

BACKGROUND: Lesions posterior to the odontoid process pose a surgical challenge. Posterolateral approaches to this region are considerably risky for the spinal cord. Transoral approaches are limited in terms of exposure and can also carry morbidity. METHODS: We describe a focused endoscopic endonasal approach (EEA) for removing an osteochondroma located dorsal to the odontoid process. The surgical pearls and pitfalls using stepwise image-guided EEA cadaveric dissections are highlighted defining the importance of various craniocervical junction (CCJ) lines on imaging. CONCLUSION: EEA to CCJ can be offered, with lower morbidity than other approaches, even for lesions that extend posterior and caudal to the odontoid process. Radiologic predictors of exposure and intraoperative techniques to enhance endoscopic visualization are discussed.

Surgical nuances of the expanded endoscopic anterior skull base craniectomy for hyperostotic meningioma resection.

BACKGROUND: The rostral expanded endoscopic approach (EEA) to anterior cranial fossa (ACF) has several advantages over transcranial/craniofacial surgery, providing early access to the vascular supply of tumors and reducing morbidities of craniotomy especially that of brain retraction. This article presents endoscopic landmarks and nuances for a wide ACF corridor, with stepwise image-guided dissections highlighting surgical tricks and techniques to enhance surgical safety. METHODS: We describe an expanded endoscopic endonasal anterior skull base craniectomy for a recurrent large olfactory groove hyperostotic meningioma, with correlated cadaveric dissections. CONCLUSION: The widening of rostral EEA can provide a safe and feasible route to access ACF. This article highlights the specific landmarks in endoscopic anatomy with reference to the angle of visualization and bayonetted instruments.

Techniques and challenges of the expanded endoscopic endonasal access to the ventrolateral skull base during the "far-medial" and "extreme medial" approaches.

BACKGROUND: Expanding the ventrolateral skull base corridor from the midline of lower clivus to the petroclival fissure is a challenging endonasal surgical task. Resection of lytic lesions like chondrosarcoma can cause cranial nerve morbidities and injury of ICA, necessitating accurate knowledge of correlative endoscopic anatomy with stereotactic landmarks. METHODS: We describe an extended endoscopic endonasal approach (EEA) for a right petroclival chondrosarcoma with the demonstration of ipsilateral surgical landmarks with contralateral normal correlates, using a stepwise comparative image-guided cadaveric dissection study. CONCLUSION: EEA for lytic lesions like chondrosarcomas needs to address brain shift and displacement of ICA, posing a chance for cranial nerve morbidities and ICA injury. Meticulous utilization of intraoperative stereotactic landmarks can help avoid and mitigate surgical complications.

Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability.

The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as interleukin-1ß (IL-1ß), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1ß on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1ß signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.

Development and Implementation of an Inpatient Otolaryngology Consultation Service at an Academic Medical Center.

OBJECTIVES: To design and implement a formal otolaryngology inpatient consultation service that improves satisfaction of consulting services, increases educational opportunities, improves the quality of patient care, and ensures sustainability after implementation. METHODS: This was a retrospective cohort study in a large academic medical center encompassing all inpatient otolaryngology service consultations from July 2005 to June 2014. Staged interventions included adding fellow coverage (July 2007 onward), intermittent hospitalist coverage (July 2010 onward), and a physician assistant (October 2011 onward). Billing data were collected for incidences of new patient and subsequent consultation charges. The 2-year preimplementation period (July 2005-June 2007) was compared with the postimplementation periods, divided into 2-year blocks (July 2007-June 2013). Outcome measures of patient encounters and work relative value units were compared between pre- and postimplementation blocks. RESULTS: Total encounters increased from 321 preimplementation to 1211, 1347, and 1073 in postimplementation groups (P < 0.001). Total work relative value units increased from 515 preimplementation to 2090, 1934, and 1273 in postimplementation groups (P < 0.001). CONCLUSIONS: A formal inpatient consultation service was designed with supervisory oversight by non-Accreditation Council for Graduate Medical Education fellows and then expanded to include intermittent hospitalist management, followed by the addition of a dedicated physician assistant. These additions have led to the formation of a sustainable consultation service that supports the mission of high-quality care and service to consulting teams.

Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice.

Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 µm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 µm/m3, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.

Epidemiologic Trends in Human Papillomavirus-Associated Sinonasal Squamous Cell Carcinoma.

Importance: Sinonasal squamous cell carcinoma (SNSCC) is the most commonly encountered cancer within the sinonasal cavity. Ongoing research has sought to ascertain the potential role of human papillomavirus (HPV) in the pathogenesis of SNSCC. Objective: To assess trends in HPV-associated and HPV-independent SNSCC over time, including assessment of clinical demographics, treatment patterns, and survival. Design, Setting, and Participants: This cohort study used patient data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database between 1975 and 2018. Anatomic sites with a greater predilection for HPV positivity (ie, nasal cavity, ethmoid sinus) were used as a surrogate for HPV-associated SNSCC; meanwhile, patients with SNSCC in the other subsites were classified into the HPV-independent group. Data were analyzed from August 2022 to May 2023. Main Outcomes and Measures: Clinical demographics and mortality trends over time were described for the HPV-associated and HPV-independent groups and further stratified according to stage on presentation. Results: The study population consisted of 3752 patients with SNSCC (mean [SD] age at diagnosis, 65.7 [13.3] years; 2417 [64.4%] male), with 1983 (52.9%) having HPV-associated SNSCC and 1769 (47.1%) with HPV-independent SNSCC. Patients with HPV-associated subsites compared with patients with HPV-independent SNSCC were more likely to present with localized disease (838 [42.3%] vs 162 [9.2%]), whereas more patients in the HPV-independent group than HPV-associated group presented with regional disease (1018 [57.5%] vs 480 [24.2%]). Incidence-based mortality was stable over time within the HPV-associated group (0.32%) and, conversely, showed a significant decrease within the HPV-independent group (-2.29%). Patients with HPV-associated SNSCC had a higher 5-year overall survival when compared with the HPV-independent group (62% vs 35% [difference, 27 percentage points; 95% CI, 23-31 percentage points]). The better 5-year overall survival in the HPV-associated group vs HPV-independent group was present across all disease stages (localized: hazard ratio [HR], 2.67; 95% CI, 1.96-3.65; regional: HR, 1.53; 95% CI, 1.29-1.82; and distant: HR, 1.97; 95% CI, 1.52-2.55). Conclusions and Relevance: This cohort study showed that the proportion of HPV-associated SNSCC rose over time associated with both a rise in the proportion of nasal cavity SNSCC and a decrease in HPV-independent maxillary sinus SNSCC. These data suggest that HPV-associated SNSCC has a distinct demographic and prognostic profile, given the improved survival seen in patients with HPV-associated SNSCC.

Anatomical Variations of the Ascending Pharyngeal Artery: Implications for Endoscopic Surgery in the Parapharyngeal Space.

Objectives: The ascending pharyngeal artery (APA) travels with the parapharyngeal internal carotid artery (pICA) in the parapharyngeal space (PPS). This study aimed to investigate the anatomical variations of the APA, and to explore their implications for endoscopic surgery in the PPS. Methods: Dissection of the APA in the PPS was performed on 10 cadaveric specimens (20 sides). The relationship between APA and PPS tumors was retrospectively reviewed in 20 patients, attempting to ascertain the APA during the resection of 10 pre-styloid and 10 retro-styloid PPS tumors. Results: During the cadaveric dissections, the APA was identified at the medial, posteromedial, or bilateral aspects of the pICA in 12 (60%) and 4 (20%) sides, respectively. In the remaining 4 sides (20%), the APA branched into several subcategory arteries lying at the medial and lateral aspects of the pICA. Branches of the APA were observed in 13/20 sides (65%). Two branches were found in 9/13 sides and 3 branches in 4/13, respectively. The APA was only identifiable in 1/10 (10%) of pre-styloid tumors, a patient with basal cell adenoma. In contrast, the APA was encountered surrounding the pICA in 8/10 (80%) of patients with retro-styloid tumors, all of which were schwannomas. No inadvertent injury of the APA or the pICA occurred in this cohort. Conclusions: With identification of the ascending pharyngeal artery on preoperative magnetic resonance imaging, it may serve as an additional landmark during the endoscopic extirpation of tumors arising in the PPS.

Increasing radiation therapy and lower survival for human papillomavirus-related oropharynx cancer associated with a shift to community cancer center care.

BACKGROUND: Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. METHODS: This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. RESULTS: The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). CONCLUSIONS: Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.