Expanding HPV-Related Multiphenotypic Sinonasal Carcinoma Morphologic and Genotyping Profile

This study characterized a cohort of 52 cases of HPV-related multiphenotypic sinonasal carcinoma (HMSC) from Latin America, integrating clinicopathological, immunohistochemical, HPV genotyping, and prognostic data. HMSC predominantly arose in the nasal cavity (n=20/38.46%) of patients in their sixth decade, with equal sex distribution (n=26/50%) and frequent symptomatic presentation. Histopathologically, all tumors displayed epithelial surface dysplasia (n=52/100%). Most cases featured solid proliferations (n=25/48.08%) of basaloid cells (n=46/88.46%), with frequent tumor necrosis (n=41/75.85%). Perineural (n=5/9.62%) and vascular invasion (n=3/5.77%) were uncommon. Most patients underwent surgical excision (n=19/46.34%). Recurrence occurred in 15 of 42 cases (35.71%), although the majority remained disease-free at last follow-up (n=35/85.37%). Immunohistochemistry revealed diffuse p16 expression and variable positivity for squamous and myoepithelial markers. The Ki-67 proliferation index was high overall (median 50.1 [30.7 to 66.3]). HPV genotyping identified HPV 33 as the predominant subtype (n=34/65.38%), with a subset of cases demonstrating coinfections (n=9/17.30%). Survival analysis revealed excellent outcomes (5 y OS, DSS, and DFS at 90.1%, 89.7%, and 82.4%, respectively), although regional and distant metastases and HPV coinfections correlated with poorer survival. Our findings underscore the necessity of individual-subtype-specific HPV genotyping to characterize HMSC pathogenesis and refine prognostic stratification accurately.