Updates in the cause of sinonasal inverted papilloma and malignant transformation to squamous cell carcinoma.

PURPOSE OF REVIEW The purpose of this study was to give an overview of recently published articles investigating the cause of inverted papilloma and possible mechanisms mediating malignant transformation into squamous cell carcinoma (SCCa). RECENT FINDINGS Inverted papilloma is a sinonasal tumour that is benign in nature, but has a tendency for local invasion, recurrence and malignant degeneration. Its pathogenesis has not been elucidated and the etiological role for human papillomavirus virus (HPV) has been controversial. Recent reports have varied in detection method (mRNA ISH, DNA ISH and PCR amplification of highly conserved regions of the viral genome), ranging from 0 to 100%. Advances in meta-genomics have permitted detection of HPV viral signatures that were previously cost-prohibitive, and there appears to be a potential role for both low-risk and high-risk in the cause of the disease. Activating EGFR mutations have also been identified to be correlated with malignant transformation, which may be exclusive of HPV infection. Furthermore, more comprehensive approaches in detecting genomic markers have been reported, with HOX-related genes and epithelial-mesenchymal-transition-related gene sets appear to be differentially upregulated. SUMMARY Sinonasal inverted papilloma is a diverse disease that is predominantly benign, but it harbours the potential for malignant degeneration in the SCCa with cause yet to be elucidated. Current evidence supports a potential role for high-risk HPV in a subset of SCCa, with the role of low-risk HPV yet to be defined. Historic studies of individual and small groups of molecular markers have not consistently adequate characterize signalling pathways underpinning the oncogenesis, and comprehensive genomic studies are needed to better understand the disease.