Sinonasal Papillomas and Their Malignant Transformation

Sinonasal papillomas are benign epithelial tumours arising in the nasal cavity and paranasal sinuses. They comprise three histological subtypes—exophytic, inverted and oncocytic—with inverted sinonasal papilloma (ISP) being the most locally aggressive and prone to recurrence and malignant conversion. ISP typically presents with unilateral nasal obstruction, epistaxis and sinusitis-like symptoms. Histopathologically, inverted growth of the epithelium into the underlying stroma distinguishes it from other sinonasal masses. Although the overall risk of carcinoma arising within ISP ranges from 5% to 15%, this malignant transformation often leads to sinonasal squamous cell carcinoma with a more challenging clinical course. Molecular drivers include activating mutations in the epidermal growth factor receptor (EGFR), integration of high-risk human papillomavirus genotypes and dysregulation of key signalling pathways such as PI3K/AKT and MAPK. Imaging plays a critical role in preoperative planning and surveillance, with recent advances in magnetic resonance imaging and CT-based radiomics improving diagnostic accuracy. Surgical resection remains the cornerstone of treatment, and the choice of endoscopic versus external approaches is guided by tumour stage, origin site and extension. Adjuvant radiotherapy may be considered in cases with high-grade transformation or positive margins. Long-term follow-up is essential to detect recurrence and early malignant change, underscoring the global importance of standardised diagnostic protocols and targeted therapeutic strategies.

Research from Nature Portfolio

Recent experimental work has established the first organotypic in vitro model recapitulating inverted sinonasal papilloma development. Using an air–liquid interface culture of nasal epithelial cells harbouring specific EGFR exon 20 duplications, researchers have demonstrated characteristic endophytic growth patterns. Functional assays revealed that these mutations hyperactivate the PI3K/AKT and MAPK pathways, driving increased cell migration and invasion. Targeted inhibition of PI3K or MEK markedly reduced these malignant phenotypes, providing a preclinical basis for novel targeted therapies in cases harbouring EGFR exon 20 alterations.

Sinonasal Papillomas and Their Malignant Transformation publication trend

The graph below shows the total number of articles in sinonasal papillomas and their malignant transformation across all publications each year (not limited to Nature Index journals).

Technical terms

Sinonasal papilloma: A benign epithelial tumour developing in the nasal cavity and paranasal sinuses, classified into exophytic, inverted and oncocytic subtypes.

Inverted papilloma: A subtype characterised by inward folding of epithelium into the stroma, associated with higher recurrence and risk of carcinoma.

Malignant transformation: The process by which a benign lesion acquires genomic and phenotypic alterations to become invasive cancer.

Epidermal growth factor receptor (EGFR): A cell-surface receptor whose activating mutations can promote neoplastic growth and serve as therapeutic targets.

Radiomics: A computational method extracting quantitative imaging features to enhance diagnostic and prognostic assessments of lesions.

References

1. Classification of nasal polyps and inverted papillomas using CT-based radiomics. Insights into Imaging (2023).
2. An in vitro model and the underlying pathways of sinonasal inverted papilloma development. Scientific Reports (2023).
3. High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma. Cancer Research (2015).
4. Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16INK4a in sinonasal diseases. Infectious Agents and Cancer (2015).
5. Origin site‐based staging system of sinonasal inverted papilloma for application to endoscopic sinus surgery. Head & Neck (2018).
6. Risk Factors of Recurrence and Malignant Transformation of Sinonasal Inverted Papilloma. BioMed Research International (2017).