Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

Application of Time-Driven Activity-Based Costing for Head and Neck Microvascular Free Flap Reconstruction.

OBJECTIVE: Traditional hospital accounting fails to provide an accurate cost of complex surgical care. Here we describe the application of time-driven activity-based costing (TDABC) to characterize costs of head and neck oncologic procedures involving free tissue transfer. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. METHODS: An analysis of head and neck oncologic procedures involving microvascular free flap reconstruction from 2018 to 2020 (n = 485) was performed using TDABC methodology to measure cost across operative case and postoperative admission, using quantity of time and cost per unit of each resource to characterize resource utilization. Univariate and generalized linear mixed models were used to examine associations between patient and hospital characteristics and cost of care delivery. RESULTS: The total cost of care delivery was $41,905.77 ± 21,870.27 with operating room (OR) supplies accounting for only 10% of the total cost. Multivariable analyses identified significant cost drivers including operative time, postoperative length of stay, number of return trips to the OR, postoperative complication, number of free flaps performed, and patient transfer from another hospital or via emergency department admission (P < .05). CONCLUSION: Operative time and postoperative length of stay, but not operative supplies, were primary drivers of cost of care for head and neck oncology cases involving free tissue transfer. TDABC offers granular cost characterization to inform cost optimization through unused capacity identification and postoperative admission efficiencies.

Upfront neck dissection for treatment selection and improvement in quality of life as a novel treatment paradigm for deintensification in HPV+ OPSCC.

PURPOSE: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II de-escalation trial for patients with HPV+OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve quality of life without compromising survival. METHODS: Patients with T1-3, N0-2 HPV+ OPSCC underwent an upfront neck dissection with primary tumor biopsy. Patients with a single lymph node less than six centimeters, with no extracapsular spread(ECS), and no primary site adverse features underwent transoral surgery (Arm A). Patients who had two or more positive lymph nodes with no ECS, or those with primary site adverse features were treated with radiation alone (Arm B). Patients who had ECS in any lymph node were treated with chemoradiation (Arm C). The primary endpoint was quality of life at 1 year compared to a matched historical control. RESULTS: Thirty-four patients were enrolled and underwent selective neck dissection. Based on pathologic characteristics, 14 patients were assigned to arm A, 10 patients to arm B, and 9 to arm C. A significant improvement was observed in HNQOL compared to historical controls (-2.6 vs -11.9, p=0.034). With a median follow-up of 37 months, the 3-year overall survival was 100% and estimated 3-year estimated progression free survival was 96% (95% CI: 76-99%). CONCLUSION: A neck dissection driven treatment paradigm warrants further research as a de-intensification strategy.

Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects.

BACKGROUND: Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30 years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. METHODS: We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. RESULTS: The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. CONCLUSION: We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.

Evaluation of the safety and effectiveness of robot-assisted neck dissections.

BACKGROUND: Robot-assisted neck dissection (RAND) for the management of the regional lymphatic basin offers the potential for improved cosmesis and reduced lymphedema. While RAND has been previously described, functional outcome and oncologic control rates need further elucidation. METHODS: A retrospective, matched cohort study of neck dissections completed at UPMC from 2017 to 2021 was conducted. RAND was identified and matched to open neck dissections (open) in a 1:2 ratio. Matching characteristics included primary cancer site, pre-operative clinical N-stage, age at time of surgery, HPV status, and previous chemoradiation treatment (salvage vs. nonsalvage procedure). Additional information was collected on patient demographics, surgery characteristics, and outcomes. Comparisons were made using t-test, chi-square test, Fisher's exact test, and Kaplan-Meier Wilcoxon (KMW) test with p < 0.05 indicating significance. RESULTS: Overall, RAND and open groups had similar distributions of age, gender, BMI, primary site of cancer, HPV status, clinical N-stage, clinical T-stage, known neck disease prior to procedure, prior chemoradiation therapy, and level(s) of neck dissection. Surgically, RAND procedures yielded less drainage on average (124 mL in RAND vs. 220 mL in open approaches; p = 0.01). There was no difference in the rates of complications, estimated blood loss, or number of lymph nodes obtained. There were also no differences in the rates of adjuvant therapy. Long term, there were no differences in the rates of local, locoregional, and distant recurrence of primary disease between RAND and open procedures. There were also no differences in postprocedure disease-free survival time (KMW p-value = 0.32; HR [of RAND compared with open] = 0.62). Similarly, there were no statistical differences in the overall survival of RAND patients when compared with the open group (75 vs. 58.9 months; HR = 0.11, p = 0.87). CONCLUSION: This study is the first to report the long-term effectiveness of robot-assisted surgery compared with the traditional, open approach. In addition to well-known cosmetic benefits, robot-assisted surgery may also offer patients a reduction in uncomfortable drains and improved effects from lymphedema. Overall, this study provides initial data that the RAND may be considered as an alternative approach to open surgery.

Association of preoperative thyroid hormone replacement with perioperative complications after major abdominal surgery.

OBJECTIVE: To determine the association between preoperative thyroid hormone replacement and complications following major abdominal surgery. METHODS: A retrospective case series was performed of patients enrolled in the Michigan Surgical Quality Collaborative (MSQC) who underwent major abdominal surgery at an academic institution over a 10-year period. The principal explanatory variable was preoperative thyroid hormone replacement. Primary outcomes were morbidity, mortality and length of stay. RESULTS: 2700 patients were identified. On multivariate analysis correcting for established predictors of operative morbidity, patients on preoperative thyroid replacement had a 1.5- fold increased risk of serious morbidity(p â€‹= â€‹0.01), and a 1.7- fold greater risk for serious sepsis(p â€‹= â€‹0.04). Thyroid replacement was associated with longer length of stay(p â€‹< â€‹0.001). While there was a high degree of missing data for surgical approach (31.1 â€‹% missing data), results suggest that patients on thyroid hormone replacement were more likely to undergo an open rather than minimally invasive surgery(p â€‹< â€‹0.01). Open surgery was associated with greater risk of serious morbidity(p â€‹= â€‹0.003) and longer length of stay(p â€‹< â€‹0.001). CONCLUSIONS: Preoperative thyroid hormone replacement independently predicts operative morbidity and length of stay following major abdominal surgery.

Team-Based Surgical Approach to Head and Neck Microvascular Free Flap Reconstruction.

Importance: Because microvascular free flap reconstruction is increasingly used to restore function in patients with head and neck cancer, there is a growing need for evidence-based perioperative care. Objective: To assess the association of different team-based surgical approaches with intraoperative and postoperative outcomes for patients undergoing head and neck free flap reconstruction. Design, Setting, and Participants: This retrospective cohort study of 733 patients was conducted at an academic tertiary care medical center. Head and neck oncologic procedures involving microvascular free flap reconstruction with available intraoperative data collected from January 1, 2000, to December 31, 2021, were included. Main Outcomes and Measures: Patient characteristics including demographic characteristics and comorbid conditions, operative variables, length of stay, and postoperative outcomes were measured. Descriptive statistics and effect size measures were performed to compare the 3 intraoperative surgical team approaches, specifically single surgeon, separate 2-team approach, and integrated 2-team approach; 1:1 nearest neighbor matching without caliper was performed to compare single- vs 2-team and separate and integrated 2-team approaches. Effect size measures including Cramer V for dichotomous variables, the Kendall W coefficient of concordance for ordinal variables, and η2 for continuous variables were reported with 95% CIs to describe precision. Results: Among 733 cases, there were no clinically significant differences in patient demographic characteristics, clinicopathologic characteristics, and choice of free flap reconstruction based on intraoperative surgical team approach. The mean (SD) age was 58.7 (12.4) years, and 514 were male (70.1%). In terms of operative and postoperative variables, there was a difference in operative times and intraoperative fluid requirements among the 3 different techniques, with the integrated 2-team approach demonstrating a mean reduction in operative time of approximately 2 hours (η2 = 0.871; 95% CI, 0.852-0.887; mean [SD] operative time = 541 [191] minutes for the single-surgeon approach, 399 [175] minutes for the integrated 2-team approach, and 537 [200] minutes for the separate 2-team approach) and lower fluid requirements of greater than 1 L (η2 = 0.790; 95% CI, 0.762-0.817). In both unadjusted analyses and propensity score matching, there were no clinically significant differences in terms of ischemia time, use of pressors, postoperative complications (including free flap failure, number of return trips to the operating room, length of stay, or 30-day readmission) based on intraoperative team approach. Conclusions and Relevance: Findings suggest that the integrated 2-team surgical approach for complex head and neck microvascular reconstruction can be used to safely decrease operative time, with no difference in postoperative outcomes.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

Color Match Following Free Flap Surgery in Head and Neck Reconstruction: A Colorimetric and Aesthetic Analysis.

BACKGROUND: Many options for free tissue transfer have been described for head and neck reconstruction. While functional outcomes remain paramount, aesthetic considerations like color match can be equally consequential for patient quality of life. It is important to understand differences in color match based on flap donor site for head and neck reconstruction. METHODS: A retrospective review was performed of patients who underwent head and neck reconstruction with free tissue transfer at a tertiary care academic medical center between November 2012 and November 2020. Patients with documented pictures of their reconstruction and external skin paddles were considered. Patient demographics and surgery specific factors were recorded. Objective differences in color match were obtained by calculating the International Commission on Illumination Delta E 2000 (dE2000) score. Standard univariate descriptive statistics and multivariable statistical analyses were performed. RESULTS: Lateral arm, parascapular, and medial sural artery perforator (MSAP) free tissue transfer performed favorably compared to other donor sites, whereas anterolateral thigh flaps had the highest average dE2000 scores. Differences in dE2000 scores were mitigated by post-operative radiation to the flap site and with increasing time beyond 6 months post-operatively. CONCLUSIONS: We provide an objective assessment of external skin color match in patients undergoing free tissue transfer for head and neck cancer by donor site. MSAP, lateral arm, and parascapular free flaps performed well compared to traditional donor sites. These differences are more significant at the face and mandible when compared to the neck, but diminish 6 months after surgery and with post-operative radiation to the free flap skin paddle.

Development of a high-performance multi-probe droplet digital PCR assay for high-sensitivity detection of human papillomavirus circulating tumor DNA from plasma.

OBJECTIVES: To develop a high-performance droplet digital PCR (ddPCR) assay capable of enhancing the detection of human papillomavirus (HPV) circulating tumor DNA (ctDNA) in plasma from patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). MATERIALS AND METHODS: Plasma samples from subjects with HPV+ OPSCC were collected. We developed a high-performance ddPCR assay designed to simultaneously target nine regions of the HPV16 genome. RESULTS: The new assay termed 'ctDNA HPV16 Assessment using Multiple Probes' (CHAMP- 16) yielded significantly higher HPV16 counts compared to our previously validated 'Single-Probe' (SP) assay and a commercially available NavDx® assay. Analytical validation demonstrated that the CHAMP-16 assay had a limit of detection (LoD) of 4.1 copies per reaction, corresponding to < 1 genome equivalent (GE) of HPV16. When tested on plasma ctDNA from 21 patients with early-stage HPV+ OPSCC and known HPV16 ctDNA using the SP assay, all patients were positive for HPV16 ctDNA in both assays and the CHAMP-16 assay displayed 6.6-fold higher HPV16 signal on average. Finally, in a longitudinal analysis of samples from a patient with recurrent disease, the CHAMP-16 assay detected HPV16 ctDNA signal âˆ¼ 20 months prior to the conventional SP assay. CONCLUSION: Increased HPV16 signal detection using the CHAMP-16 assay suggests the potential for detection of recurrences significantly earlier than with conventional ddPCR assays in patients with HPV16+ OPSCC. Critically, this multi-probe approach maintains the cost-benefit advantage of ddPCR over next generation sequencing (NGS) approaches, supporting the cost-effectiveness of this assay for both large population screening and routine post-treatment surveillance.

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of 18F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation. METHODS AND MATERIALS: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC. All patients started definitive CRT to 70 Gy in 35 fractions, and those who met de-escalation criteria on midtreatment FDG-PET at fraction 10 completed treatment at 54 Gy in 27 fractions. We report the acute toxicity and patient-reported outcomes for 59 patients with a minimum follow-up of 3 months. RESULTS: There were no statistically significant differences between baseline patient characteristics in the standard and de-escalated cohorts. There were 28 of 59 (47.5%) patients who met FDG-PET de-escalation criteria and collectively received 20% to 30% less dose to critical organs at risk known to affect toxicity. At 3 months posttreatment, patients who received de-escalated CRT lost significantly less weight (median, 5.8% vs 13.0%; P < .001), had significantly less change from baseline in penetration-aspiration scale score (median, 0 vs 1; P = .018), and had significantly fewer aspiration events on repeat swallow study (8.0% vs 33.3%, P = .037) compared with patients receiving standard CRT. CONCLUSIONS: Approximately half of patients with early-stage p16+ OPSCC are selected for de-escalation of definitive CRT using midtreatment FDG-PET biomarkers, which resulted in significantly improved rates of observed acute toxicity. Further follow-up is ongoing and will be required to determine whether this de-escalation approach preserves the favorable oncologic outcomes for patients with p16+ OPSCC before adoption.

Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16-positive oropharynx cancer.

BACKGROUND: We sought to characterize early changes in CD8+ tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial. METHODS: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8+ tumor-infiltrating lymphocytes and transcriptomes were assessed. RESULTS: One week after cetuximab, five patients (62.5%) had an increase in CD8+ cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8+ cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways. CONCLUSIONS: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content.

The Larry Tube: Customized 3D Printed Laryngectomy Tubes Following Total Laryngectomy.

OBJECTIVE: To determine whether a custom laryngectomy tube can improve airway symptoms in total laryngectomy patients with atypical anatomy who are unable to use commercial laryngectomy tubes. Furthermore, to exemplify the power of customizable 3D printed medical devices when combined with the expanded access pathway through the FDA. METHODS: A custom-fabricated laryngectomy tube, manufactured at in-house clinical engineering labs, was utilized for each patient following typical laryngectomy tube protocols. All participants had previously undergone a total laryngectomy. Patients were selected based on critical airway obstruction posing potentially life-threatening scenarios while using commercially available laryngectomy tubes. RESULTS: For all patients involved, there were no further airway obstruction complications or events, and they reported a subjective, significant improvement in comfort after placement of the custom laryngectomy tube. CONCLUSION: Custom laryngectomy tubes can provide patients with atypical anatomy relief from airway obstructions and improve comfort when commercial options fail to address the anatomic restriction. The process used to develop custom laryngectomy tubes may be relevant for other diseases and patients with atypical anatomies through the expanded access pathway.

Neurotization of the radial forearm free flap improves swallowing outcomes in hemiglossectomy defects.

BACKGROUND: We examined the effect of free tissue neurotization on speech and swallowing outcomes for patients undergoing reconstruction of hemiglossectomy defects with a radial forearm free flap (RFFF). METHODS: A retrospective study was performed in patients with oral cavity squamous cell carcinoma undergoing a hemiglossectomy and reconstruction with a RFFF. Functional outcomes including nutritional mode, range of liquids and solids, and speech understandability were analyzed 1-year post-treatment. RESULTS: Eighty-four patients were included in this analysis, 41 of whom had neurotized flaps (49%). No significant differences in demographic or clinical variables were seen between the neurotized and non-neurotized groups. On multivariate analysis controlling for BMI, flap area, and N-classification, patients with neurotized flaps were significantly more likely to have normal range of liquids and solids and less likely to have a G-tube. CONCLUSIONS: Neurotization of RFFF reconstructing hemiglossectomy defects results in decreased G-tube dependence and improved range of liquids and solids.

Cross-legged modification for medial sural artery perforator flap harvest.

When thin and pliable free tissue is needed, the medial sural artery perforator (MSAP) flap provides an excellent option with minimal donor site morbidity. However, among its pitfalls include difficult patient positioning and surgeon ergonomics throughout the harvest. We describe a novel positioning technique that may significantly improve surgeon ergonomics and ease of MSAP flap harvest. A cross-legged modification may eliminate many of the issues associated with the classic frog-leg position. While the patient is cross-legged, the surgeon is afforded a normal field of view that is closer to their body, while simultaneously providing support to the lateral side of the gastrocnemius muscle. This pictorial essay describes this positioning technique and subsequent harvest. By incorporating a more ergonomic cross-legged position during flap elevation, many of thedrawbacks of the MSAP flap could be eliminated.

Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma.

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.