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Purpose: To explore the association between intraoperative surgical margin sampling by the frozen sections and recurrence in inverted papilloma surgery., Methods: A multicenter, retrospective study of patients who underwent attachment-oriented IP resection in four tertiary care medical centers with a minimal follow-up of 36 months., Results: The study included 220 surgeries with a mean follow-up period of 49 months (range 36-204). The endoscopic approach was used in all but 4 cases; 73% of procedures were primary. Overall recurrence was 10.45% (n = 23). Squamous cell carcinoma was found in 5 cases (2.2%). Intraoperative margin sampling was obtained in 145 cases. There was no difference in the recurrence rate between frozen section and no-frozen section groups (p = 0.44). Furthermore, margin sampling in various sites of tumor origin, in cases with concomitant nasal polyps (p = 0.53) and in revision cases (p = 0.08) showed no correlation with recurrence. In 26 cases when the surgery was extended following a positive frozen section, there was a significantly higher recurrence rate (OR = 6.94)., Conclusions: According to our results, intraoperative margin sampling did not affect the recurrence rate of IP, and therefore, its routine use should be questioned., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the correlation between the ability to predict the attachment site of sinonasal inverted papilloma by computed tomography and the long-term surgical outcome., Study Design: Retrospective cohort study., Setting: Five tertiary medical centers., Methods: Study patients underwent attachment-oriented resection of inverted papilloma. The primary outcome was tumor recurrence., Results: Among 195 patients eligible for the study, focal hyperostosis was recognized on computed tomography in 65% (n = 127), in 71% of primary cases (n = 101), and in 50% of revision procedures (n = 26). There was a trend for a higher incidence of squamous cell carcinoma among the patients without detectable hyperostosis ( P = .051). Location of hyperostosis coincided with the actual tumor attachment site in 114 patients (90%). Discordance between these parameters did not differ significantly ( P = .463) between 11 primary and 2 revision cases. The overall rate of recurrence was 9.7% (n = 19), with a mean time to recurrence of 20 months (range, 7-96 months). The rate of recurrence did not correlate with any of the following: tumor stage, surgical approach, presence of squamous cell carcinoma, whether the surgery was primary or revision, and the presence or location of focal hyperostosis on computed tomography. Inverted papilloma recurred significantly more often (38.5%) when the intraoperative findings of the tumor attachment site did not match the location of hyperostosis observed on computed tomography (odds ratio, 6.5; 95% CI, 1.78-23.66)., Conclusion: Detectability of focal hyperostosis on preoperative computed tomography does not affect the long-term outcome of inverted papilloma resection.

Purpose: Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC) is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors., Experimental Design: We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP) tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score-the Maximum-Minimum Exon Score (MMES)--designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort., Results: After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed TP63 as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (LAMA3 and DST) validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001)., Conclusion: Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.

Objectives: The incidence of oral tongue squamous cell carcinoma is rising in young patients. This study evaluated the clinical, pathological, and prognostic characteristics of oral tongue squamous cell carcinoma in the under-30-year age group., Materials and Methods: The computerized database of the Department of Otolaryngology-Head and Neck Surgery of a tertiary, university-affiliated medical center was searched for all patients with oral tongue squamous cell carcinoma treated by glossectomy with curative intent in 1996-2012. Data were collected by chart review., Results: Of the 113 patients identified, 16 (14%) were aged ⩽30years at presentation and 62 (55%) >60years. Mean follow-up time was 30months. Comparison by age group revealed no sex predilection and no differences in histologic grade or rates of advanced T-stage, perineural and vascular invasion, or nodal extracapsular extension. Rates of node-positive disease were 75% in the younger group and 19% in the older group (p<0.001). Kaplan-Meier analysis yielded no between-group difference in disease-free or overall survival. Recurrence was documented in a similar proportion of patients (38% and 29.9%, respectively), but half the recurrences in the younger group were distant versus none in the older group (p=0.01) All younger patients with recurrent disease died within 16months of its appearance compared to 50% 3-year disease-specific survival in the older group., Conclusions: Oral tongue squamous cell carcinoma is more advanced at presentation in younger than in older patients, with higher rates of regional metastases and distant failure. Recurrent disease is more aggressive, with a fatality rate of 100%., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Failure rate of surgery for early tongue carcinoma remains high. We sought to identify patterns of failure and recurrence risk factors., Methods: Data review was carried out on 50 patients treated for early tongue carcinoma (T1/2N0M0); surgery was unsuccessful in 11 of these patients. All patients underwent transoral resection of the tongue tumor and prophylactic neck dissection (supraomohyoid)., Results: Tumor recurred within 3 to 18 months. Nine died of disease. Four had failure in neck level 4, 6 in level 1, and 1 simultaneously in level 1 and locally. Most tumors were moderately differentiated. Average depth was 6.64 mm., Conclusions: We report 11 patients with early tongue carcinoma who failed local excision with neck dissection. Failures occurred in level 4 (4 patients) and level 1 (7 patients). This group may benefit from extended neck surgery. Sex, age, stage, and depth of tumor were not significantly different in the group with treatment failure. Tumors in the group with treatment failure were more poorly differentiated., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented., Experimental Design: In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC) tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene., Results: From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines., Conclusion: In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

Background and Aims: Squamous cell carcinoma (SCC) of the oral tongue is one of the most frequent head and neck cancers. The over-70-year age group is the fastest growing segment of the population. Age, however, is not considered a prognostic factor in oral tongue SCC. This study investigated the clinical and histopathological characteristics, disease course, and outcome of SCC of the oral tongue in patients over 75 years old compared with younger patients., Methods: We reviewed the files of 85 patients with histologically proven SCC of the oral tongue who were treated in our department in 1992-2007 and followed for a minimum of 2 years. Findings were compared between those aged 75 years or more and younger patients., Results: Twenty-eight patients (33%) were aged 75 to 94 years (average 80.5±4.5 yrs), including 14 who were over 80 years old, and 57 patients were aged 15-74 years (average 51.1±18.2 yrs). No statistically significant differences were found between the groups in clinical or histopathological characteristics or patient outcome. The 5-year disease-free survival rate was 65% for patients over 75 and 58% for younger patients. Corresponding rates for 5-year disease-specific survival were 69% and 70%. These differences were not statistically significant., Conclusions: Patients over 75 with oral tongue SCC should be managed like younger patients in terms of clinical staging and co-morbidities. They should be given a chance for treatment, as their prognosis is no different from that of younger patients.

Objective: To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue., Design: Retrospective, case control study., Setting: A major tertiary referral centre., Participants: Eighty-five patients with oral tongue squamous cell carcinoma with at least 2 years of follow-up., Main Outcome Measurements: Clinical and histopathological staging, disease-free survival, disease-specific survival and overall survival., Results: Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between-group differences in 5-year disease-free, disease-specific, and overall survival., Conclusion: In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age-related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established.

Objectives: The management of advanced laryngeal cancer has evolved in the last century, from total laryngectomy to chemoradiation. The aim of this study was to examine our experience with supracricoid partial laryngectomy as a possible solution for patients with advanced laryngeal tumours, with a focus on the oncological safety of the procedure and the functionality of the preserved larynges., Study Design: We reviewed the medical records of patients with laryngeal cancer who had undergone primary or salvage supracricoid partial laryngectomy at our department between 1998 and 2004., Results: Twenty-three patients treated with supracricoid partial laryngectomy for endolaryngeal squamous cell carcinoma were identified. Median follow-up time was 35 months. Twelve patients had advanced laryngeal tumours. Eight patients were radiation failures. These factors were not associated with increased local recurrence or with decreased survival., Conclusion: Supracricoid partial laryngectomy appears to be a feasible option for the treatment of laryngeal tumours, even in the advanced stage or after failure of radiation therapy.