Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review

Eur Arch Otorhinolaryngol. 2017 Aug;274(8):2991-3000. doi: 10.1007/s00405-017-4571-2. Epub 2017 Apr 21.


Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7-11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.

Keywords: Molecular biomarkers; Schneiderian papilloma; Sinonasal inverted papilloma; Sinonasal papillomas; Target therapies.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Carcinoma, Squamous Cell* / prevention & control
  • Cell Transformation, Neoplastic / genetics*
  • Cyclooxygenase 2 / genetics*
  • ErbB Receptors / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Metallothionein / genetics
  • Molecular Targeted Therapy
  • Nasal Mucosa / pathology
  • Nose Neoplasms* / genetics
  • Nose Neoplasms* / pathology
  • Nose Neoplasms* / therapy
  • Papilloma, Inverted* / genetics
  • Papilloma, Inverted* / pathology
  • Papilloma, Inverted* / therapy
  • Papillomavirus Infections / epidemiology
  • Paranasal Sinus Neoplasms* / genetics
  • Paranasal Sinus Neoplasms* / pathology
  • Paranasal Sinus Neoplasms* / therapy
  • Risk Factors


  • MT2A protein, human
  • Metallothionein
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • EGFR protein, human
  • ErbB Receptors