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Background: Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features., Methods: We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis., Results: All pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC-alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase-9 (HR = 1.6) abundances with PSM., Conclusions: Pathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations., (© 2023 Wiley Periodicals LLC.)

Background: Oropharyngeal squamous carcinomas cause significant morbidity and mortality. Poor prognosticators include lymphovascular and perineural invasion. Extratumoral phenotypes of these histologic findings confer worse prognoses., Methods: We report eight cases of recurrent oropharyngeal cancer with diffuse extratumoral lymphovascular invasion (ELVI) or extratumoral perineural invasion (EPNI) and review the existing literature., Results: On salvage resection for recurrence following primary radiation or chemoradiation, six patients manifested ELVI and two showed EPNI. These patterns conferred difficulty with complete surgical clearance; final pathologic analysis demonstrated positive margins for all eight patients. The six patients with ELVI were p16+ and the two with EPNI were p16-. Currently, two patients are deceased and six patients are alive at an average follow-up of 17.4 months. Of the six living patients, 2 have a new recurrence and are in hospice while 4 have no evidence of disease., Conclusions: ELVI and EPNI have received little consideration in the literature as unique histopathologic features of oropharyngeal squamous carcinoma. We present the first series on these adverse extratumoral features in recurrent disease. We call attention to these unique histologic features in the setting of recurrent oropharyngeal cancer to encourage others to track the results of therapeutic intervention and to identify successful strategies for treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vivian Su is currently employed by the Thyroid Head and Neck Cancer Foundation. Gabriella T. Seo, Monica H. Xing, and Lily Greenberg were previously employed by the Thyroid Head and Neck Cancer Foundation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Adenoid cystic carcinoma (ACC) is a commonly encountered salivary gland malignancy. However, it rarely occurs in the gingiva, an area generally thought to be devoid of minor salivary glands. We present a case occurring in this unusual site and review other reported cases., Methods: A 56 year-old male presented with a right-sided mandibular toothache for 1 year and underwent dental extraction. Due to persistent pain, follow up examination revealed a large gingival lesion. A biopsy was positive for adenoid cystic carcinoma., Results: The patient underwent a complete right segmental mandibulectomy and was reconstructed with a fibular osteocutaneous free flap. Three months postoperatively, during the planning for adjuvant radiation therapy, the patient developed pain in the left mandible. Imaging revealed extensive involvement of the left native mandible. Deep bone biopsies in several areas of the left mandible revealed ACC. He then underwent a complete left hemi-mandibulectomy and reconstruction with a fibular osteocutaneous free flap. Tensor fascia lata suspension slings were placed due to concern for an open mouth deformity attributable to disruption of bilateral masticator slings. He will undergo adjuvant radiation therapy. Our review of the literature revealed 50 cases of gingival ACC published since 1972. Disease recurrence and distant metastases were noted in several patients, occurring at the latest after 30 years follow-up., Conclusions: Given its indolent behavior, high proclivity for late recurrence and metastasis, and overall infrequency, ACC represents a pathology that requires early diagnosis and comprehensive long-term surveillance. While ACC is well described in oral cavity sites with high densities of minor salivary glands, it is not commonly seen in the gingiva. As such, gingival ACC may display a unique biological and/or clinical character. We offer the first literature review of this rare entity.

Open-mouth deformity after mandibular resection presents a challenge for surgeons and patients, contributing to significant functional and cosmetic morbidity. We present an innovative surgical technique to prevent or correct open-mouth deformity. Tensor fascia lata slings were utilized in combination with maxillomandibular fixation to surgically correct or prevent open-mouth deformity in four patients who had previously undergone mandibulectomy or at the time of a contralateral mandibulectomy following prior hemimandibulectomy and reconstruction. Two patients achieved favorable outcomes, including oral competence and improved resting jaw position, while open-mouth deformity could not be corrected for one patient. Another patient remains in the early postoperative period following a secondary procedure to correct open-mouth deformity. Open-mouth deformity is a functional/aesthetic problem that has not been addressed in the literature. Use of tensor fascia lata slings to suspend the mandible is a novel approach to the surgical management of open-mouth deformity., (© 2022 Wiley Periodicals LLC.)

The palatal island flap is reliable for single-staged reconstruction of select oral defects. However, fistula formation is a disruptive potential complication. The authors employed this technique in five patients and present a representative case of a 65-year-old female with a left-sided palatal salivary neoplasm. The patient underwent resection and was reconstructed utilizing a combination of the buccal fat pad and palatal island flap. Four of the five patients healed uneventfully. One patient experienced partial loss of the marginal zone of the palatal island flap which successfully granulated and did not lead to an oroantral fistula. The representative patient recovered uneventfully. At 2 weeks, she felt well, with no evidence of fistula. The anterior palate demonstrated early mucosalization. We present the novel, combined use of the palatal island flap and buccal fat pad flap to create a two-layer closure and describe its advantages for posterior palate reconstruction., (© 2022 Wiley Periodicals LLC.)

Background: Neck carcinoma of unknown primary (CUP) is a frequent scenario. Transoral robotic mucosectomies (TORM) of pharynx have increased rate of primary identification, but come with cost of treatment delay., Methods: We reviewed patients who underwent CUP protocol from 2014 to 2020. Patients with cervical nodes carcinoma and failure to localize a primary source were classified as CUP. We determined primary identification rate and postoperative complications., Results: We included 65 patients underwent TORM. Surgical approach consisted of lingual and/or palatine tonsillectomies. The primary detection rate was 49.2%. Average weight reduction was 2.5 ± 4.3 kg. The average number of days from consultation to definitive treatment was 52.2 ± 18.3., Conclusion: A systematic approach to patients with CUP showed a promising primary identification rate compared to panendoscopy alone. TORM carries a small risk of complications. The benefits of primary identification must be weighed with the morbidity and delay to definitive treatment., (© 2022 Wiley Periodicals LLC.)

Background: Devascularization of the parathyroid glands is generally accepted as the most common mechanism for iatrogenic hypocalcemia, a frequently seen complication of both total and completion thyroidectomy procedures. Much has been written about iatrogenic hypoparathyroidism, but few papers have precisely delineated the arterial supply of the parathyroid glands and the common anatomical variations that may impact parathyroid preservation during thyroid surgery., Methods: We offer an illustrated review and discussion of the only two anatomic studies published in the medical literature focusing on parathyroid vasculature. In addition, we examine current techniques of parathyroid identification, preservation, and classification., Findings: A surgical technique that preserves the parathyroid arteries is vital to preserving the viability of the parathyroid gland(s) during thyroid surgery. In 1907, Halsted and Evans described a technique of ligating the distal branches of the thyroid arteries beyond the origin of the parathyroid arteries, a technique termed ultra-ligation. In 1982, Flament et al.. reported three distinct anatomical variations of the parathyroid arteries which place the parathyroid blood supply at risk for devascularization during thyroid surgery. Our review also highlights novel techniques that aid surgeons in identification and assessment of the parathyroid glands., Conclusions: Recognition of the variations of parathyroid anatomy and their potential to lead to devascularization aids thyroid surgeons in their pursuit of parathyroid preservation. An awareness of the variety of novel parathyroid identification and preservation techniques can assist surgeons to achieve this goal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Primary malignancies arising in the external auditory canal (EAC) are rare and usually are treated surgically. We review techniques to reconstruct the EAC following ablative surgery, and introduce a rarely utilized tragal skin flap which has particular advantages for reconstruction of limited anterior EAC defects., Methods: The terms "tragal flap", "external auditory canal", "preauricular tragal flap", "reconstructive techniques" were searched on PubMed and Google Scholar., Results: Our review identified one description of a tragal flap to reconstruct the EAC following resection of a malignancy. We add an additional case of a preauricular tragal flap to reconstruct the anterior EAC following resection of a recurrent basal cell carcinoma located in the EAC that led to a circumferential defect., Conclusion: There are several surgical techniques that can be utilized to reconstruct the EAC. We describe a novel tragal flap used to reconstruct the anterior EAC following resection of a recurrent tumor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The fibular free flap (FFF) is commonly used for head and neck bony reconstruction. Ossification of the vascular pedicle has been reported but is an uncommon complication of this procedure. Ossification of the pedicle with FDG avidity has not been identified in the literature. Here we present a case of FDG avid free flap ossification seen on PET/CT imaging in a patient who developed trismus after fibular free flap reconstruction of a maxillary defect for a primary squamous cell carcinoma of the palate. The FDG avidity of the free flap ossification and trismus were both concerning for recurrent squamous cell carcinoma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pharyngoesophageal stenosis (PES) is a serious complication that substantially impacts functional outcomes and quality of life (QOL) for up to a third of head and neck cancer patients who undergo radiotherapy. Dysphagia is often multifactorial in nature and is a devastating complication of treatment that impacts patients' QOL, general health and overall wellbeing. The authors detail the clinical presentation, risk factors, imaging characteristics, preventive measures, and multimodality treatment options for PES., Methods: The authors present a comprehensive management algorithm for PES, including treatment by dilation, stenting, spray cryotherapy and dilation, and reconstructive treatment options utilizing different pedicled and free flaps., Results: The authors advocate for a thorough assessment of the extent and degree of pharyngoesophageal involvement of PES to determine the optimal management strategy., Conclusions: The development of post treatment dysphagia requires appropriate imaging and biopsy, when indicated, to rule out the presence of persistent/recurrent cancer. Multidisciplinary management by a team of physicians well-versed in the range of diagnostic and therapeutic interventions available for PES is critical to its successful management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Head and neck squamous cell carcinoma (HNSCC) affects various anatomical sites, which often dictates whether the cancer is managed with primary surgery or radiation. This study aimed to assess differences in single nucleotide variation (SNV), copy number, mRNA abundance, methylation, and tumor microenvironment (TME) between HPV-negative oral cavity (OC), oropharyngeal (OPC), hypopharyngeal (HPC), and laryngeal (LC) cancers within The Cancer Genome Atlas (TCGA)., Methods: We downloaded the clinical information and molecular data for the TCGA HNSCC cohort from the data portal and published literature. The TME was estimated using mRNA abundance data. We conducted our analyses within the Bioconductor statistical framework in the R environment. CNA and mRNA abundance results were correlated and grouped with SNV results for downstream pathway analysis., Results: LC had a higher mutational burden than OC and OPC (p <10 -4 ). LC tumors were enriched in CSMD3, NSD1, DCHS2 and ANK2 SNVs, while OC tumors were enriched in CASP8 SNVs (FDR < 0.1). LCs were enriched for neuronal and glycosylation pathways, while OCs were enriched for extracellular matrix pathways. B cells and endothelial cells were more abundant in LC while monocytes were more abundant in OC (FDR < 0.1). OPC was the most hypoxic, followed by OC then LC (FDR < 0.05). OC had greater methylation of Hox genes than LC. Subsite analysis revealed that oral tongue cancers had fewer CASP8 and FBN2 mutations and higher dendritic cell abundance than other oral cavity cancers., Conclusions: We identified significant genomic, transcriptional, and microenvironmental differences between HPV-negative HNSCC. Further study is warranted to determine if these findings portend differential response to specific treatment modalities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear., Methods: Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels., Results: Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC., Conclusion: These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC.

Background: Recently, reanalysis of The Cancer Genome Atlas study demonstrated that human papillomavirus (HPV) genotypes in head and neck cancers other than HPV-16 have inferior survival to HPV-16-positive tumors. We aimed to examine the association of HPV subtypes and survival in a large cohort of patient samples from our institution., Methods: Fresh frozen primary site biopsy samples were collected either in clinic or at the time of surgery. Patient demographic, staging, and survival data were also collected. Tumors were tested for HPV subtypes by quantitative polymerase chain reaction (qPCR). Univariable and multivariable analyses were performed using Cox proportional hazards regression., Results: 280 patient biopsy samples were collected between 2011 and 2017. Mean ± standard deviation (SD) age was 61.9 ± 11.1 years and most patients (78%) were male. The majority of cancers were of the oral cavity (60%) or oropharynx (25%) and 30% had HPV-positive disease. Median follow-up was 3.76 years and 96/280 patients (34%) developed recurrences. Patients with p16-positive versus negative disease had significantly improved 5-year overall survival (OS, 77.6% vs. 53.3%; p =0.009) and progression-free survival (PFS, 67.3% vs. 41.0%, p =0.006). Similarly improved 5-year OS and PFS were observed for patients with HPV-positive versus negative disease (65.0% vs. 55.0%, p =0.084; 53.3% vs. 43.2%, p =0.072, resp.). Patients with HPV-16 compared to other HPV diseases had worse 5-year OS and PFS (62.1% vs. 88.9%, p =0.273; 49.0% vs. 88.9%, p =0.081, resp.)., Conclusions: In contrast to the data derived from The Cancer Genome Atlas, patients with HPV-16 tumors trended towards decreased PFS and OS compared with tumors driven by other HPV genotypes. Further larger multi-institutional studies are necessary to understand the relationship between other HPV genotypes and survival in head and neck squamous cell carcinomas., Competing Interests: The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication., (Copyright © 2021 Hedyeh Ziai et al.)

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

Background: Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT., Methods: Consecutive cases of early T-stage (T1-T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria., Results: A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026)., Conclusions: Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

Anaplastic thyroid cancer (ATC) is a rare, but nearly uniformly fatal disease that is typically resistant to chemotherapy and radiation. Alternative strategies to target this cancer at a molecular level are necessary in order to improve dismal outcomes for ATC patients. We examined the effects of flavopiridol, a CDK inhibitor, in a panel of ATC cell lines. When cell lines were treated over a ten-point concentration range, CAL62, KMH2 and BHT-101 cell lines had a sub micromolar half-maximal inhibitory concentration, while no effect was seen in the non-cancerous cell line IMR-90. Flavopiridol treatment resulted in decreased levels of the cell cycle proteins CDK9 and MCL1, and induced cell cycle arrest. Flavopiridol also decreased the in vitro ability of ATC cells to form colonies and impeded migration using a transwell migration assay. In vivo, flavopiridol decreased tumor weight and tumor volume over time in a patient-derived xenograft model of ATC. Given the observed in vitro and in vivo activity, flavopiridol warrants further investigation for treatment of ATC., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Survival in head and neck squamous cell carcinoma (HNSCC) has been associated with patient sex, typically with males experiencing poorer outcomes. It is unclear if this disparity is based in divergent tumor biology. We analyzed the TCGA HNSCC cohort to uncover disparities in the somatic single nucleotide variation (SNV), copy number alteration (CNA) and mRNA abundance profiles between males and females. Critically, we stratified our results by tumor HPV status to control for this significant confounder., Methods: SNV, CNA and mRNA abundance differences between males and females were compared separately for the HPV-positive (n = 67) and negative (n = 431) TCGA HNSCC cohorts. Overall survival outcomes were compared in males and females in both HPV-positive and HPV-negative subsets of patients., Results: Females were found to have poorer overall survival than males (p = 0.048), largely due to higher rates of HPV-positive disease among men. SNV analysis revealed that in HPV-positive disease, there were no differences by sex after accounting for the false discovery rate (FDR). In HPV-negative tumors, BRWD3 mutations occurred more frequently in the tumors of female patients compared to males after adjusting for the FDR (p = 0.02). Further, HPV-negative BRWD3 mutant tumors were found to have significantly worse 5-year overall survival compared to wildtype on multivariate analysis (p = 0.02). There were 88 heterozygous deletions and 14 amplifications that were differentially altered between male and female HPV-negative tumors and associated with expression changes. Pathway analysis of these genes revealed that tumors from males were enriched in five pathways including chemokine and phosphophatidylinositol signaling., Conclusions: Reanalysis of the TCGA HNSCC dataset stratified by sex revealed that males in this cohort had a significant survival advantage, due to a higher proportion of HPV-positive disease. Mutations in BRWD3 were more frequent in HPV-negative tumors of females and were associated with poorer overall survival. BRWD3 may represent a novel biomarker of patient outcomes, but will require additional validation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project. We attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort., Methods: Patient demographic data along with data from final pathology was collected. Tumor DNA was analyzed using a custom Illumina targeted sequencing panel. Five high-risk HPV types were tested by qPCR. Statistical analyses were used to identify associations between patient outcome and mutational status., Results: High-risk HPV types were identified in 7% of cases; HPV status was not associated with survival. Mutations were identified in TP53, TERT promoter, & PIK3CA. Mutations in TP53 were significantly associated with poorer overall survival on multi-variate analysis ( p  = 0.03)., Conclusions: Mutations in TP53 were associated with poor patient survival. Expanding our sample size may identify further predictors of outcome to direct customized cancer care., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients.

Background and Significance: Anaplastic thyroid cancer (ATC) is rare, but its clinical presentation is often dramatic and aggressive and is nearly uniformly fatal. Oncolytic viral therapy is a potential strategy to improve outcomes for patients suffering with this disease., Methods: Seven established ATC cell lines were infected with a panel of poxviruses to identify which virus had the most potential as an oncolytic agent. These included myxoma, vaccinia, and tanapox viruses, all modified to express green fluorescence protein (GFP). Viral proliferation was assessed by fluorescence and viral amplification. The effect on cell line growth was assessed by the Presto Blue metabolic assay and a live-dead assay. A replication assay was performed to assess the production of infectious progeny. An additional five ATC cell lines were tested using the assays described above for susceptibility to vaccinia virus., Results: ATC cell lines were differentially susceptible to each virus. Vaccinia virus was superior to myxoma and tanapox viruses for the control of anaplastic thyroid cancer in vitro. Although subsequent investigation using an expanded panel of cell lines revealed differential susceptibility to vaccinia virus, effective control of cell proliferation was still achieved using higher titers., Conclusions: Vaccinia virus was the most potent of the tested poxviruses and was highly effective in controlling proliferation and inducing cell death in ATC cell lines. The efficacy of these viruses offers hope for improving outcomes for patients suffering with ATC., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The role of the HPV E6/E7 oncogenes in head and neck squamous cell cancer (HNSCC) has been studied extensively, but the role of the viral E5 protein remains poorly understood. Studies in cervical cancer indicate that E5 increases epidermal growth factor receptor (EGFR) recycling to the cell surface and enhances growth factor signal transduction., Objective: This study was designed to examine the relationship between HPV E5, EGFR, and survival in HPV-positive HNSCC., Study Design: A retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. HPV E5 and EGFR expression was measured by reverse transcriptase real-time PCR., Results: The majority of oropharyngeal tumor samples (59/82, 72%) were HPV-16 positive. Among the HPV-positive tumors, highly variable E5 expression was detected from early polycistronic transcripts. Tumors with high E5 expression levels had significantly higher EGFR levels (p=0.03). High E5 levels were correlated with improved recurrence-free survival, but not overall survival (p=0.02 and 0.71, respectively), whereas high EGFR was strongly associated with decreased recurrence-free and overall survival (p<0.001 and 0.006 respectively). Multivariate analysis revealed E5 and EGFR to be the strongest predictors of recurrence-free survival (p<0.01)., Conclusions: HPV E5-encoded transcripts are variably expressed in HPV-positive HNSCC and this is correlated with EGFR expression in HPV-positive OPC. However, E5 and EGFR independently predict recurrence-free survival in opposing manners. These findings require further validation to determine if E5 and EGFR are useful biomarkers to stratify treatment intensity for patients with HPV-positive HNSCC., (Copyright © 2014. Published by Elsevier B.V.)

Background: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide. Existing therapies for advanced tumors have high failure rates and can have severe consequences in terms of pain, disfigurement, and poor speech and swallowing function. New treatment strategies are needed to improve outcomes for patients suffering with this disease and oncolytic viruses represent a promising approach., Methods: We infected six well-characterized HNSCC cell lines (Cal27, Detroit562, FaDu, SCC4, SCC15, SCC25), with increasing doses of a panel of poxviruses (including myxoma, vaccinia, raccoonpox and tanapox viruses) modified to express green fluorescence protein to determine which virus was the most effective oncolytic agent in cell-based assays., Results: While myxoma, raccoonpox and tanapox displayed differing efficacy in the panel of cell lines, vaccinia virus was the most potent of the tested poxviruses and was highly effective in controlling cell growth in all cell lines., Conclusion: Oncolytic poxviruses, particularly vaccinia virus, were effective in killing HNSCC in vitro and hold promise as potential treatments for patients with HNSCC., (Copyright © 2013 S. Karger AG, Basel.)