Sinonasal Inverted Papillomas: Predictors of Recurrence and Malignant Transformation

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and malignant transformation in IPs. We retrospectively analyzed 73 patients with histologically confirmed IPs that were treated at three tertiary ENT centers, including radiologic data, HPV DNA detection and p16 immunohistochemistry. Univariate analysis was used to identify factors associated with recurrence and malignant transformation, and restricted exploratory multivariable logistic regression models were used to assess recurrence while minimizing overfitting. Fourteen recurrences (19%) were associated with longer symptom duration (p = 0.003), smoking (p = 0.03), advanced Krouse stage (III-IV) (p < 0.001), frontal sinus origin (p = 0.02), HPV+ DNA (50% vs. 22%, p = 0.048), and p16 loss/reduced expression (p = 0.006). Nine recurrences transformed into carcinoma (12%) and were associated with smoking (p = 0.01). HPV+ was not associated with malignancy (p = 1.00). Recurrence was associated with the advanced stage of the IP, tobacco use, longer symptom duration, frontal sinus origin, HPV+, and p16 loss/reduced expression.