Background: Sinonasal squamous cell carcinoma (SNSCC) is rare in the general population. No clear and consistent etiologic correlation between human papillomavirus and SNSCC has yet been delineated in literature. p16 is a tumour suppressor protein used as a surrogate marker for HPV. This study aims to evaluate the relationship between p16 overexpression in SNSCC and its role in prognosis and survival. Methods: A population-based retrospective analysis was performed using prospectively collected data from the Northern Alberta Head and Neck Tumour Board, Alberta Cancer Registry, and Alberta Cancer Research Biobank. p16 overexpression was analyzed from pathologic sample of patients meeting study criteria, and participants were dichotomized by status. Subsequently, nonparametric analysis of demographics, initial staging, and initial treatment were performed, and a Kapan-Meier curve was developed to assess differences in survival. Results: 16 patients were included in analysis. p16 overexpression was seen in 68.8% of patients. p16 positive and negative groups were comparable for age, gender, smoking status, stage, and treatment. A statistically significant five-year survival advantage was observed in patients with p16 positive SNSCC (p = 0.013). Conclusions: This is the first Canadian study to demonstrate a high prevalence of p16 positivity in SNSCC and its presence denoting a statistically significant survival advantage. Results demonstrate a previously unconfirmed role of oncogenic HPV in SNSCC.

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are currently targets for diagnosis and treatment. The most common type of cancer originated in the sinonasal tract are sinonasal squa-mous cell carcinomas (SNSCC), which presents different histological patterns and variable his-tological aggressiveness. A significant number of alterations have been reported in sinonasal tu-mors, including deficiencies in the SwItch/Sucrose non-fermentable (SWI/SNF) chromatin remod-eling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMAR-CA4/BRG1 and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tu-mors with distinctive high-grade morphology and fatal prognosis. Objective: To identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carci-nomas and its association with morphology and survival. Methods: A total of 1582 SNSCC cases were analyzed, selecting those with high-grade malignancy morphology, which were then evalu-ated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCC, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCC), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expres-sion for SMARCB1 (NKSCC 33%, KSCC 21.9%) and SMARCA4 (NKSCC 14.6%, KSCC 12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that the mosaic expression of INI1 in NKSCC exhibited a worse prognosis compared to intact carcinomas and was similar to SMARCB1-deficent carcinoma.