Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma A Systematic Review and Meta-analysis

Question Are there differences in survival between de novo and inverted papilloma-associated sinonasal squamous cell carcinoma pathogenesis? Findings In this systematic review and meta-analysis of 26 studies with 1194 unique patients, those with de novo sinonasal squamous cell carcinoma (dnSCC) had almost a 2-fold increased risk of mortality compared with those with inverted papilloma-associated squamous cell carcinoma (IPSCC). Meaning These findings suggest that compared with dnSCC, IPSCC may represent a less aggressive form of malignancy; if future prospective studies corroborate these results, de-escalation of IPSCC treatment may be considered to limit morbidity. This systematic review and meta-analysis uses data from studies retrieved from an Ovid Medline, Embase, Scopus, and Cochrane Library database search to investigate survival differences between de novo and inverted papilloma-associated sinonasal squamous cell carcinoma pathogenesis. Importance Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I-2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I-2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I-2 = 0%). Conclusions and Relevance This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Automated summary

By conducting a systematic review and meta-analysis on 1194 unique patients, it was found that patients with de novo sinonasal squamous cell carcinoma had nearly a 2-fold increased risk of mortality compared to those with inverted papilloma-associated squamous cell carcinoma. This suggests that IPSCC may represent a less aggressive form of malignancy when compared to dnSCC, potentially allowing for treatment de-escalation based on histopathology pending further validation from larger studies.