Risk Factors for Malignant Transformation in Inverted Sinonasal Papilloma: A Systematic Review and Meta-Analysis

Background/Objectives: Inverted sinonasal papilloma (IP) is a benign epithelial proliferation that can recur and undergo malignant transformation. We performed a systematic review and meta-analysis to answer the following question: what are the risk factors for malignant transformation in IP? Methods: A search was performed in PubMed and Embase databases. Numbers of affected individuals in exposed versus non-exposed individuals, or odds ratio values, were compared for each specific risk factor examined. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. To assess the overall quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analyses were conducted using the fixed-effects and the random effects models. Heterogeneity of the results was assessed by I-2 statistic output. Meta-analyses and forest plots were obtained using Review Manager (RevMan) software version 5.4. Results: After examining 1875 results (942 from PubMed; 933 from Embase), 26 articles were selected. Among the 26 selected articles, the number of cases examined ranged from 14 to 162. All studies examined a population of 1271 IPs, with a carcinoma incidence of 230/1271 (18.1%). Three meta-analyses were performed for the following risk factors: smoking, alcohol, and HPV. Using the fixed-effects model, significant values were obtained for smoking (p = 0.002) and HPV (p < 0.001), with moderate and low quality of evidence, respectively. Alcohol did not reach statistical significance (p = 0.95). Conclusions: This study demonstrates that both smoking and HPV are risk factors for IP malignant transformation. Possible interventions include smoking cessation and HPV vaccination in individuals affected by IP.