Defining the Role of HPV in the Malignant Transformation of Sinonasal Inverted Papillomas: A Meta-analysis

Objectives: To date, there is still a significant debate of the role of human papilloma virus (HPV) infection in transformation of inverted papillomas (IPs) to squamous cell carcinoma (SCC). This study was designed to determine if the presence of HPV in a sinonasal inverted papilloma increases the risk of malignant transformation to IPSCC.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRIMSA) guidelines, 19 high-quality case–control and cohort studies with tissue-diagnosed IP or IPSCC and HPV diagnosis were analyzed. Odds ratios and 95% confidence intervals were calculated using the Mantel-Haenszel method with correction for random effects. An assessment of study bias, publication bias, and a sensitivity analysis were also performed.

Results: Nineteen studies with minimal bias met our inclusion criteria for quality and identified HPV infection in an IP. The pooled data revealed a strong association with progression to malignancy with an unweighted, pooled OR of 2.32 (95% CI: 1.48–3.58) and a weighted OR of 8.51 (95% CI: 6.89–10.13). A sensitivity analysis revealed that no single study contributed significantly to our pooled OR calculations (OR: 7.08–9.03). Subgroup analyses stratified by publication date, nucleic acid target for HPV, HPV detection method, study sample size, and region all demonstrated a significant, positive association of HPV with IPSCC.

Conclusion: HPV has a strong and significant association with malignant transformation of IPs. While HPV testing is not currently the standard of care for IPs, these data suggest a link between the two and that routine testing for HPV may change surveillance for HPV-positive patients.

Publication History

Article published online:
12 February 2021