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Introduction: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years., Methods: Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA)., Results: WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05)., Conclusions: Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver., (© 2022 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Background: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control., Methods: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems., Results: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively., Conclusion: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers., (© 2018 Wiley Periodicals, Inc.)

Background: The 8th edition American Joint Committee on Cancer (AJCC8) provides the same nodal staging system for mucosal and cutaneous squamous cell carcinoma of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an adverse prognostic criterion. This study evaluates the prognostic efficacy of the AJCC8 pathologic nodal staging system (pN) for HNcSCC., Methods: Univariate analysis of 382 patients with metastatic HNcSCC staged according to both the 7th (AJCC7) and the 8th edition staging systems., Results: The AJCC7 pN3 category was associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83-16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54-7.58; P = 0.002) as compared with pN1. However, no difference was observed between pN1, pN2, and pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34-1.67; P = 0.478) or OS (HR 0.88; 95% CI: 0.51-1.51; P = 0.648)., Conclusion: The AJCC8 performed poorly as a prognostic indicator for patients with metastatic HNcSCC in this cohort. HNcSCC would benefit from a staging system that accounts for its unique biologic characteristics distinct from mucosal SCC., (© 2017 Wiley Periodicals, Inc.)

Background: The rectus myocutaneous free flap (RMFF) is used for medium to large maxillectomy defects. However, in patients with central obesity the inset could be difficult due to the bulk from excessive layer of adipose tissue. We describe a modification of the RMFF for patients with excessive central obesity with a flap consisting of adipose tissue with minimal rectus muscle; the musculo-adipose rectus free flap (MARF)., Methods: Five cases of MARF reconstruction were performed between 2003 and 2013, with patients' body mass indexes ranging from 29.0 to 41.2 kg/m 2 . All patients had sinonasal tumor, of which three were adenoid cystic carcinoma, one squamous cell carcinoma, and one melanoma. Four patients had Codeiro IIIb defects and one had Codeiro II defect. Using the MARF technique, the maxillectomy defect was obliterated with vascularized adipose tissue overlying the rectus muscle and was trimmed to fit the maxillectomy defect. The adipose tissue was allowed to granulate and mucosalize., Results: The volume of adipose tissue harvested was between 120 and 160 mL. All flaps survived with no requirement for re-exploration. Complete oro-nasal separation was achieved in all patients. The time to commencement of oral intake ranges from 5 to 15 days. One patient developed seroma and one developed wound breakdown on the donor site. The length of stay at the hospital ranges from 9 to 22 days. On follow-up ranging 7.5-32.8 months, two patients died from their malignancies. The other three patients were able to tolerate oral soft diet., Conclusion: The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017., (© 2015 Wiley Periodicals, Inc.)

Background: Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub-categorization of PNI improves risk stratification., Methods: PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease-specific survival (DSS) as the primary endpoints., Results: PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high-risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post-operative radiotherapy (PORT)., Conclusions: Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation., (© 2014 Wiley Periodicals, Inc.)