Factors Associated with Postoperative Recurrence in Inverted Sinonasal Papilloma: A Single-Center Cohort Study

Background/Objectives: Inverted sinonasal papilloma (ISP) is a benign tumor with clinically important risks of recurrence and malignant transformation. We investigated factors associated with postoperative recurrence and the clinical significance of human papillomavirus (HPV) DNA detection. Methods: We retrospectively reviewed 104 surgically treated patients with histologically confirmed ISP (2006–2024). Clinical and radiological factors, HPV genotype and viral load, and p16, p53, and Ki-67 expression were evaluated. Recurrence analysis included 86 patients with at least 12 months of total clinical follow-up. Results: Seven patients (8.1%) developed recurrence. Median total clinical follow-up in the recurrence-analysis cohort was 46.5 months. Frontal sinus involvement and attachment-site hyperostosis were associated with recurrence in an exploratory two-variable Cox model, with wide confidence intervals. An additional model incorporating Krouse stage failed to converge. HPV DNA was detected in 21/104 tumors (20.2%): 11 low-risk and 10 high-risk HPV-positive tumors. Viral load was quantifiable in five tumors (0.3–65.0 E6 copies/ng genomic DNA); the remaining 16 were below the quantification limit of 0.25 copies/ng. No significant association between HPV status and recurrence was demonstrated. Two tumors showed p16 overexpression, including one high-risk HPV-positive tumor; no consistent HPV-related immunohistochemical pattern was identified. Conclusions: Frontal sinus involvement and attachment-site hyperostosis were associated with recurrence in this cohort. With only seven events, the findings are exploratory and require validation. A clinically relevant HPV association cannot be excluded, and HPV transcriptional activity cannot be inferred from these data.