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

Educational Objective
To qualitatively and quantitatively assess survival outcomes of sinonasal de novo nasal squamous cell carcinoma and squamous cell carcinoma arising from inverted papilloma and directly compare survival between the 2 cohorts based on the published literature.
1 Credit CME
Key Points

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.


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%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 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; I2 = 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.

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Article Information

Accepted for Publication: November 22, 2020.

Published Online: January 28, 2021. doi:10.1001/jamaoto.2020.5261

Corresponding Author: Jake J. Lee, MD, MSCI, Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, 660 S Euclid Ave, Campus Box 8115, St Louis, MO 63110 (jakejlee@wustl.edu).

Author Contributions: Dr Lee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Lee, Pipkorn.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Lee, Peterson.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Lee, Kallogjeri.

Administrative, technical, or material support: Lee, Peterson, Embry.

Supervision: Lee, Klatt-Cromwell, Pipkorn.

Conflict of Interest Disclosures: Dr Kallogjeri reported serving as statistics editor for JAMA Otolaryngology–Head and Neck Surgery outside the submitted work. No other disclosures were reported.

Funding/Support: This research was supported by grant 5T32DC000022 from the National Institute of Deafness and Other Communication Disorders within the National Institutes of Health (Drs Lee and Wamkpah) and by grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health (Mr Peterson and Mr Embry).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Kallogjeri is Statistics Editor of JAMA Otolaryngology–Head & Neck Surgery but was not involved in any of the decisions regarding review of the manuscript or its acceptance.

Additional Contributions: We thank Graham A. Colditz, MD, MPH, and Carrie Stoll, MPH, MSW, of the Washington University Division of Public Health Sciences, for their instruction on the proper conduct of systematic reviews and meta-analyses and their feedback. We also thank Carol H. Yan, MD, of the University of California, San Diego, for sharing deidentified individual patient data from her previous publication in order to support this meta-analysis. No one was financially compensated for their contributions.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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