Association of human papillomavirus infection and epidermal growth factor receptor mutations in inverted sinonasal papilloma: a systematic review and meta-analysis

Background: Although the role of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) mutations in inverted sinonasal papilloma (ISP) has been investigated, the association between HPV infection and EGFR mutations remains controversial. The meta-analysis aimed to investigate the association between HPV infection and EGFR mutations in ISP. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched (until 22 February 2025) to collect all relevant articles. The pooled proportion of co-occurrence proportion with 95% confidence interval (CI) was calculated using the inverse-variance model. In addition, subgroup analysis, assessment of publication bias, and sensitivity analyses were performed. Results: Six eligible articles, including 210 patients with ISP, were included in this study. The pooled HPV + rate was 11%(95%CI = 5%-17%), and the pooled EGFR mutations rate was 66%(95%CI = 44%-87%) in ISP. Besides, the pooled HPV + rate was 31%(95%CI = 15%-48%), and the pooled EGFR mutations rate was 52%(95%CI = 30%-73%) in ISP-SNSCC. We calculated a pooled proportion of 0.235(95%CI = 0.025–0.446, P = 0.058). The association between HPV infection and EGFR mutations remained stable in subgroup analyses. Conclusions: We found that HPV infection and EGFR mutations seem to play opposite roles in ISP malignant transformation. HPV infection is a possible etiology of ISP and is also associated with its malignant transformation. EGFR mutations in ISP demonstrate prognostic significance with EGFR wild-type ISP being associated with earlier progression to SNSCC. Our meta-analysis demonstrates that there is not mutually exclusive between HPV infection and EGFR mutations in ISP. The result suggests that both HPV infection and EGFR mutations should be considered in the management of ISP. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.