Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.

BACKGROUND: Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion. METHODS: Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures. RESULTS: IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion. CONCLUSION: We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

KEY POINTS: Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden.

A metagenomic analysis of the virome of inverted papilloma and squamous cell carcinoma.

INTRODUCTION: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma. METHODS: To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors. RESULTS: The prevalence of HPV-16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV-18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region-specific analysis, which identified the only oncogenic HPV-18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV-18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC. CONCLUSIONS: There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV-18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP.

Incidence of Sinus Inflammation After Endoscopic Skull Base Surgery in the Pediatric Population.

BACKGROUND: The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post-operative setting, including patient compliance with medical therapy and post-operative debridements, and a smaller nasal airway that may increase propensity toward scarring. Our objective for this study is to evaluate the incidence of post-operative radiographic inflammation in this patient population using the Lund-Mackay (LM) score. METHODS: A single-center, retrospective review of pediatric patients undergoing endoscopic approach to the skull base between 2009 and 2021 was performed. Demographic and clinicopathologic data and pre- and post-operative imaging were analyzed. One-way ANOVA followed by Tukey multiple pairwise comparisons statistical tests were used to compare mean LM scores between groups. RESULTS: Seventy-two patients (52 males, 20 females) were identified with a median follow-up of 27 months. All patients underwent an extended endonasal approach for resection of skull base lesions. The mean LM scores were compared between pre-operative MRI, first post-operative MRI > 30 days after surgery, and most recent post-operative MRI. One-way ANOVA was performed with significant differences noted between the groups (p < 0.001). Tukey multiple pairwise comparisons test was then performed and noted significant differences between the pre-operative and first post-operative LM (p < 0.0001) and the first post-operative and most recent LM (p < 0.0001). There was no significant difference noted between the pre-operative LM score and most recent LM score (p = 0.14). CONCLUSION: Despite concerns regarding possible subsequent development of chronic rhinosinusitis following endoscopic skull base surgery in pediatric patients, the current study suggests that transient radiographic evidence of sinus inflammation can be seen up to six months postoperatively, which appears to resolve by approximately two years after surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2014-2017, 2023.

Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review.

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.

Sinonasal Inverted Papilloma and Squamous Cell Carcinoma: Contemporary Management and Patient Outcomes.

Inverted papillomas (IP) are the most common sinonasal tumor with a tendency for recurrence, potential attachment to the orbit and skull base, and risk of malignant degeneration into squamous cell carcinoma (SCC). While the overall rate of recurrence has decreased with the widespread adoption of high-definition endoscopic optics and advanced surgical tools, there remain challenges in managing tumors that are multiply recurrent or involve vital neurovascular structures. Here, we review the state-of-the-art diagnostic tools for IP and IP-degenerated SCC, contemporary surgical management, and propose a surveillance protocol.

Long-term outcomes in sinonasal squamous cell carcinoma arising from inverted papilloma: Systematic review.

Long-term survival and recurrence patterns of squamous cell carcinoma arising from inverted papilloma (IP-SCC) have not been thoroughly investigated. Four electronic databases were searched and primary studies describing overall survival (OS), recurrence, and mean time to recurrence of patients with IP-SCC were included for review. Our search yielded 662 studies. The 28 studies selected for inclusion identified 663 patients with IP-SCC. In 596 patients with reported T classification, 439 (73.7%) were T3/T4 on presentation. Of the 650 participants with recurrence data (local, regional, and distant), 155 (23.8%) experienced a recurrence, with an aggregate mean time-to-recurrence of 24.3 months. In 565 patients with 5-year OS rates, the aggregate 5-year OS was 62%. Based on the literature to date, IP-SCC is associated with a 5-year OS rate of 62%. 23.8% of patients experienced recurrence at a mean time of 24.3 months, suggesting the need for long-term surveillance.

Deep learning classification of inverted papilloma malignant transformation using 3D convolutional neural networks and magnetic resonance imaging.

BACKGROUND: Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP-SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these 2 entities, but no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP-SCC. We explored a deep learning approach, using 3-dimensional convolutional neural networks (CNNs), to address this challenge. METHODS: Retrospective chart reviews were performed at 2 institutions to create a data set of preoperative MRIs with corresponding surgical pathology reports. The MRI data set included all available MRI sequences in the axial plane, which were used to train, validate, and test 3 CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions. RESULTS: A total of 90 patients with IP (n = 64) or IP-SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP-SCC (n = 117). The best CNN model, All-Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and receiver-operating characteristic area under the curve of 0.80 (95% confidence interval, 0.682-0.898) for test classification performance. The other 2 models, Small-All-Net and Elastic-All-Net, showed similar performance levels. CONCLUSION: A deep learning approach with 3-dimensional CNNs can distinguish IP and IP-SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP-SCC using MRIs, more data are needed before they can reach the predictive value already established by human MRI evaluation.

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma.

BACKGROUND: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. METHODS: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. RESULTS: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). CONCLUSIONS: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

Surgical Treatment of Sinonasal Mucosal Melanoma in Patients Treated with Systemic Immunotherapy.

Objective Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma. Systemic immunotherapy, including multiple newer agents, has been used to treat metastatic or unresectable disease. In this study, we examine its efficacy in locoregional control when used in conjunction with surgical resection for primary mucosal lesions. Design Present study is a retrospective review of all patients at a tertiary academic medical center with primary sinonasal mucosal melanoma and distant metastatic disease. Results A total of four patients were identified. In all cases, patients were treated with a combination of surgical resection of the primary tumor and systemic immunotherapy. Three patients were initially treated with surgery at the primary site followed by immunotherapy for distant metastases. Response to immunotherapy at the sites of primary and metastatic disease was seen in two patients. All four patients developed progression or recurrence at the primary site following initiation of immunotherapy for which they underwent surgical resection. One patient remains in follow-up without evidence of disease 20 months after initial treatment; three succumbed to the disease at 135, 37, and 16 months after initial treatment. Conclusion Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given. This case series suggests that, though immunotherapy may demonstrate efficacy in managing distant disease, surgery should remain the first-line treatment for the primary site.

Pre-intervention SNOT-22 scores predict outcomes in aspirin exacerbated respiratory disease.

PURPOSE: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD). MATERIALS AND METHODS: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis. RESULTS: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304). CONCLUSION: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics).

Updates in the cause of sinonasal inverted papilloma and malignant transformation to squamous cell carcinoma.

PURPOSE OF REVIEW: The purpose of this study was to give an overview of recently published articles investigating the cause of inverted papilloma and possible mechanisms mediating malignant transformation into squamous cell carcinoma (SCCa). RECENT FINDINGS: Inverted papilloma is a sinonasal tumour that is benign in nature, but has a tendency for local invasion, recurrence and malignant degeneration. Its pathogenesis has not been elucidated and the etiological role for human papillomavirus virus (HPV) has been controversial. Recent reports have varied in detection method (mRNA ISH, DNA ISH and PCR amplification of highly conserved regions of the viral genome), ranging from 0 to 100%. Advances in meta-genomics have permitted detection of HPV viral signatures that were previously cost-prohibitive, and there appears to be a potential role for both low-risk and high-risk in the cause of the disease. Activating EGFR mutations have also been identified to be correlated with malignant transformation, which may be exclusive of HPV infection. Furthermore, more comprehensive approaches in detecting genomic markers have been reported, with HOX-related genes and epithelial-mesenchymal-transition-related gene sets appear to be differentially upregulated. SUMMARY: Sinonasal inverted papilloma is a diverse disease that is predominantly benign, but it harbours the potential for malignant degeneration in the SCCa with cause yet to be elucidated. Current evidence supports a potential role for high-risk HPV in a subset of SCCa, with the role of low-risk HPV yet to be defined. Historic studies of individual and small groups of molecular markers have not consistently adequate characterize signalling pathways underpinning the oncogenesis, and comprehensive genomic studies are needed to better understand the disease.

Adenocarcinoma of the Sinonasal Tract: A Review of the National Cancer Database.

Background Sinonasal adenocarcinoma (SNAC) is a rare malignancy arising from mucus-secreting glandular tissue. Limited large-scale studies are available due to its rarity. We evaluated SNAC in the National Cancer Database (NCDB), a source that affords multi-institutional, population studies of rare cancers and their outcomes. Methods The NCDB was queried for adenocarcinoma in the sinonasal tract. Multivariate analyses were performed to evaluate for factors contributing to overall survival (OS). Results A total of 553 patients were identified. The cohort was composed of 59.3% males. The nasal cavity was the most common primary site, representing 44.1% of cases. About 5.7% of patients presented with nodal disease, while 3.3% had distant metastases. About 40.6% of cases presented with stage IV disease. About 73.5% of patients underwent surgery, 54.2% received radiation therapy, and 27.7% had chemotherapy. Median OS was 71.7 months, while OS at 1, 2, and 5 years was 82, 73.0, and 52%, respectively. On multivariate analysis, advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.05), Charlson-Deyo score of 1 (HR: 1.99; 95% CI: 1.20-3.30), advanced tumor grade (HR: 2.73; 95% CI: 1.39-5.34), and advanced tumor stage (HR: 2.71; 95% CI: 1.33-5.50) were associated with worse OS, whereas surgery (HR: 0.34; 95% CI: 0.20-0.60) and radiation therapy (HR: 0.55; 95% CI: 0.33-0.91), but not chemotherapy (HR: 1.16; 95% CI: 0.66-2.05), predicted improved OS. Conclusions SNAC is a rare malignancy with 5-year survival approximating 50%. Surgery and radiation therapy, but not chemotherapy, are associated with improved survival, and likely play a critical role in the interdisciplinary management of SNAC.

Disorders Involving a Persistent Craniopharyngeal Canal: A Case Series.

Objectives A persistent craniopharyngeal canal (CPC) is a rare embryologic remnant that presents as a well-corticated defect of the midline sphenoid body extending from the sellar floor to the nasopharynx. Our case series aims to describe three unique presentations of this congenital anomaly and their subsequent management. Design Retrospective review. Setting Tertiary academic medical center. Participants Patients who underwent endoscopic transnasal surgical repair of a CPC lesion. Main Outcome Measures Resolution of symptoms and surgical outcomes. Results A total of three patients were identified. The clinical presentation varied, however, all cases prompted further imaging which demonstrated a persistent CPC and associated pathologic lesion. The presentation of a persistent CPC with nasal obstruction and subsequent iatrogenic cerebrospinal fluid leak as in Case 1 demonstrates the importance of imaging in this work-up. Cases 2 and 3 in the series were representative of the larger subset of patients in the literature who present with the defect incidentally but still warrant surgical management. Nonetheless, a standard approach to diagnosis with preoperative imaging and subsequent transnasal endoscopic repair of the skull base defect was undertaken. Conclusion The persistent CPC is a rare congenital anomaly associated with diverse pathology and careful review of preoperative radiology is critical to the management. When warranted, subsequent surgical repair and reconstruction is associated with excellent postoperative outcomes.

Extraprimary Local Recurrence of Esthesioneuroblastoma: Case Series and Literature Review.

OBJECTIVES: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy arising from olfactory neuroepithelium. Recurrence typically occurs locoregionally at the primary site or in the form of cervical metastasis. Delayed local recurrence away from the initial primary site is exceedingly rare. METHODS: Retrospective review of 4 patients with histologically confirmed extraprimary local recurrence of ENB was performed with review of the literature. RESULTS: All cases initially presented with ENB isolated to the cribriform plate(s) treated with primary surgical resection and adjuvant radiotherapy. The first patient had ENB recurrence 8 years posttreatment involving the right orbit. She later developed metastases to the spine, neck, and mandible requiring composite resection and 4 courses of radiotherapy. The second patient had ENB recurrence of the dorsal septum 9 years posttreatment with cervical metastases requiring septectomy, bilateral neck dissection, and radiotherapy. The third patient had ENB recurrence 7 years posttreatment in the posterior nasopharynx requiring endonasal nasopharyngectomy. Finally, the fourth patient had ENB recurrence 12 years posttreatment in the sphenopalatine foramen, which was endoscopically resected. At the time of this review, all 4 patients were disease free at 32, 21, 4, and 24 months posttreatment follow-ups, respectively. CONCLUSIONS: This case series describes the rare phenomenon of delayed extraprimary local recurrence of histologically confirmed ENB. Treatment of extraprimary recurrences, analogous to other forms of ENB, should include primary surgical resection with adjuvant radiotherapy for generally favorable outcomes. Long-term close follow-up based on symptoms, endoscopy, and imaging is essential because of the risk of delayed recurrence.

A subset of sinonasal undifferentiated carcinoma is associated with transcriptionally active high-risk human papillomavirus by in situ hybridization: a clinical and pathologic analysis.

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy with a poor prognosis, and pathologically, it is a diagnosis of exclusion. Rendering this diagnosis can be challenging in practice because of the large number of diverse entities in the differential diagnosis. We encountered an index case of a sinonasal carcinoma otherwise diagnosable as SNUC which, on further investigation, demonstrated strong and diffuse P16 expression, as well as diffuse expression of high-risk human papillomavirus (hrHPV) RNA by in situ hybridization (ISH). We therefore hypothesized that a subset of cases previously diagnosed as SNUC may in fact harbor transcriptionally active hrHPV. We further investigated a cohort of 25 SNUC cases in our pathology archives and performed ISH for hrHPV RNA on cases that demonstrated >70% nuclear and cytoplasmic P16 expression, criteria which, in other anatomic sites, correlates strongly with the presence of hrHPV. Twelve of 25 SNUC cases were P16 positive, and of these, 5 were positive for hrHPV by ISH. Thus, 20% of all SNUC cases in this cohort harbored transcriptionally active hrHPV. Herein, we report a clinical and pathologic analysis of these cases, including differential diagnostic considerations and comparison of their clinical behavior with SNUC cases that are negative for hrHPV by ISH.

A Population-Level Analysis of Pituitary Carcinoma from the National Cancer Database.

Objectives Pituitary carcinoma is a rare entity with fewer than 200 total cases reported in the English literature. Analysis of the population-level data from the National Cancer Database (NCDB) affords the opportunity to study this poorly understood tumor type. Methods The NCDB was queried for site, histology, and metastasis codes corresponding to pituitary carcinoma. Statistical analyses were performed to determine factors associated with overall survival (OS). Results A total of 92 patients with pituitary carcinoma met inclusion criteria. The 1 and 5 years of OS for all patients was 93.3% (95% confidence interval [CI]: 88.2-98.6%) and 80.0% (95% CI: 71.6-89.4%), respectively. Patients with invasive primary tumor behavior had 1 and 5 years of OS of 69.2% (95% CI: 48.2-99.5%) and 52.7% (95% CI: 31.2-89.2%), respectively. Multivariate analysis demonstrated that compared with benign primary behavior, invasive behavior had increased all-cause mortality (hazard ratio [HR], 1,296, 95% CI: 15.1- > 2,000). Surgery without adjuvant radiation or chemotherapy was the most common therapy (48.9%), followed by no treatment (40.2%). Compared with surgery alone, no treatment had worse OS (HR, 11.83, 95% CI: 1.41-99.56). Increasing age and female sex were both associated with increased mortality. Conclusions The most common treatment for pituitary carcinoma is surgery alone followed by no surgery. Surgery alone has significantly better OS compared with no treatment. The efficacy of radiation, chemotherapy, and neurohormonal treatments needs to be examined with prospective studies.

Incidence, risk factors, and outcomes of endoscopic sinus surgery after endoscopic skull-base surgery.

BACKGROUND: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull-base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement. METHODS: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty-three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund-Mackay (LM) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. RESULTS: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre-SBS and post-SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre-SBS and post-SBS SNOT-22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013). CONCLUSION: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS.

The virome of HPV-positive tonsil squamous cell carcinoma and neck metastasis.

Oropharyngeal squamous cell carcinoma (OPSCC) represents the most common HPV-related malignancy in the United States with increasing incidence. There is heterogeneity between the behavior and response to treatment of HPV-positive oropharyngeal squamous cell carcinoma that may be linked to the tumor virome. In this prospective study, a pan-pathogen microarray (PathoChip) was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery (TORS) and neck dissection. The virome findings of primary tumors and neck lymph nodes were correlated with clinical data to determine if specific organisms were associated with clinical outcomes. A total of 114 patients were enrolled in the study. Double-stranded DNA viruses, specifically Papillomaviridae, showed the highest hybridization signal (viral copies) across all viral families in the primary and positive lymph node samples. High hybridization signals were also detected for signatures of Baculoviridae, Reoviridae, Siphoviridae, Myoviridae, and Polydnaviridae in most of the cancer specimens, including the lymph nodes without cancer present. Across all HPV signatures, HPV16 and 18 had the highest average hybridization signal index and prevalence. To our knowledge, this is the first study that has identified the viral signatures of OPSCC tumors. This will serve as a foundation for future research investigating the role of the virome in OPSCC. Further investigation into the OPSCC microbiome and its variations may allow for improved appreciation of the impact of microbial dysbiosis on risk stratification, oncologic outcomes, and treatment response which has been shown in other cancer sites.