Skip to main content

Advertisement

SpringerLink
Log in

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

  • Review Article
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Batsakis JG, Suarez P (2001) Schneiderian papillomas and carcinomas: a review. Adv Anat Pathol 8:53–64

    Article  CAS  PubMed  Google Scholar 

  2. Buchwald C, Franzmann MB, Tos S (1995) Sinonasal papillomas: a report of 82 cases in Copenhagen Country, including a longitudinal epidemiological and clinical study. Laryngoscope 105:72–79

    Article  CAS  PubMed  Google Scholar 

  3. Deitmer T, Wiener C (1996) Is there an occupational etiology of inverted papilloma of the nose and sinuses. Acta Otolaryngol (Stockh) 116:762–765

    Article  CAS  Google Scholar 

  4. d’Errico A, Zajacova J, Cacciatore A, Buratti A, Zanelli R, Alfonzo S, Beatrice F (2013) Occupational risk factors for sinonasal inverted papilloma: a case-control study. Occup Environ Med 70(10):703–708

    Article  PubMed  Google Scholar 

  5. Barnes L, Bedetti C (1984) Oncocytic Schneiderian papilloma: A reappraisal of cylindrical cell papilloma of the sinonasal tract. Hum Pathol 15:344–351

    Article  CAS  PubMed  Google Scholar 

  6. Anari S, Carrie S (2010) Sinonasal inverted papilloma: Narrative review. J Laryngol Otol 124:705–715

    Article  CAS  PubMed  Google Scholar 

  7. Maroldi R, Farina D, Palvarini L, Lombardi D, Tomenzoli D, Nicolai P (2004) Magnetic resonance imaging findings of inverted papilloma: differential diagnosis with malignant sinonasal tumors. Am J Rhinol 18:305–310

    PubMed  Google Scholar 

  8. Phillips PP, Gustafson RO, Facer GW (1990) The clinical behavior of inverting papilloma of the nose and paranasal sinuses: report of 112 cases and review of the leterature. Laryngoscope 100:463–469

    Article  CAS  PubMed  Google Scholar 

  9. Katori H, Nozawa A, Tsukuda M (2006) Histopathological parameters of recurrence and malignant transformation in sinonasal inverted papilloma. Acta Otolaryngol 126:214–218

    Article  PubMed  Google Scholar 

  10. Mirza S, Bradley PJ, Acharya A et al (2007) Sinonasal inverted papillomas: recurrence, and synchronous and metachronous malignancy. J Laryngol Otol 121:857–864

    Article  CAS  PubMed  Google Scholar 

  11. Nudell J, Chiosea S, Thompson LD (2014) Carcinoma ex-Schneiderian papilloma (malignant transformation): a clinicopathologic and immunophenotypic study of 20 cases combined with a comprehensive review of the literature. Head Neck Pathol 8(3):269–286. doi:10.1007/s12105-014-0527-7

    Article  PubMed  PubMed Central  Google Scholar 

  12. Choi JW, Kim SG, Kim YM et al (2012) Clinical and histologic features of inverted papilloma-associated malignancy. Eur Arch Otorhinolaryngol 2012(269):2349–2354

    Article  Google Scholar 

  13. Higgins J, Thompson S, Deeks J, Altman D (2002) Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy 7:51–61

    Article  PubMed  Google Scholar 

  14. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. von Buchwald C, Bradley PJ (2007) Risks of malignancy in inverted papilloma of the nose and paranasal sinuses. Curr Opin Otolaryngol Head Neck Surg 15:95–98

    Article  Google Scholar 

  16. Yoon BN, Chon KM, Hong SL, Lee JH, Kim JY, Cho KS, Roh HJ (2013) Inflammation and apoptosis in malignant transformation of sinonasal inverted papilloma: the role of the bridge molecules, cyclooxygenase-2, and nuclear factor κB. Am J Otolaryngol. 34(1):22–30

    Article  CAS  PubMed  Google Scholar 

  17. Lee GH, Yoon YH, Kim YM, Yeo MK, Liang ZL, Kim JM, Rha KS (2012) Pattern of expression of cyclooxygenase-2 in malignant transformation of sinonasal inverted papilloma. Am J Otolaryngol 33(5):585–589

    Article  CAS  PubMed  Google Scholar 

  18. Suh JD, Palma-Diaz F, Bhuta S, Wang MB (2013) COX-(2) overexpression in sinonasal inverted papilloma. Int Forum Allergy Rhinol 3(12):997–1000

    Article  PubMed  Google Scholar 

  19. Syrjanen S, Happonen RP, Virolainen E, Siivonen L, Syrjanen K (1987) Detection of human papillomavirus (HPV) structural antigens and DNA types in inverted papillomas and squamous cell carcinomas of the nasal cavities and paranasal sinuses. Acta Otolaryngol 104:334–341

    Article  CAS  PubMed  Google Scholar 

  20. Scheel A, Lin GC, McHugh JB, Komarck CM, Walline HM, Prine ME, Zacharek MA, Carey TE (2015) Human papillomavirus infection and biomarkers in sinonasal inverted papillomas: clinical significance and molecular mechanisms. Int Forum Allergy Rhinol 5(8):701–707

    Article  PubMed  PubMed Central  Google Scholar 

  21. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707

    Article  CAS  PubMed  Google Scholar 

  22. Altavilla G, Staffieri A, Busatto G, Canesso A, Giacomelli L, Marioni G (2009) Expression of p53, p16INK4A, pRb, p21WAF1/CIP1, p27KIP1, cyclin D1, Ki-67 and HPV DNA in sinonasal endophytic Schneiderian (inverted) papilloma. Acta Otolaryngol 129(11):1242–1249

    Article  CAS  PubMed  Google Scholar 

  23. Cheung FM, Lau TW, Cheung LK, Li AS, Chow SK, Lo AW (2010) Schneiderian papillomas and carcinomas: a retrospective study with special reference to p53 and p16 tumor suppressor gene expression and association with HPV. Ear Nose Throat J 89(10):E5–E12

    PubMed  Google Scholar 

  24. Katori H, Nozawat A, Tsukuda M (2006) Relationship between p21 and p53 expression, human papilloma virus infection and malignant transformation in sinonasal-inverted papilloma. Clin Oncol (R Coll Radiol) 18(4):300–305

    Article  CAS  Google Scholar 

  25. Lawson W, Schlecht NF, Brandwein-Gensler M (2008) The role of the human papillomavirus in the pathogenesis of Schneiderian Inverted papillomas: an analytic overview of the evidence. Head Neck Pathol 2:49–59

    Article  PubMed  PubMed Central  Google Scholar 

  26. Beck JC, McClatchey KD, Lesperance MM, Esclamado RM, Carey TE, Bradford CR (1995) Human papillomavirus types important in progression of inverted papilloma. Otolaryngol Head Neck Surg 113:558–563

    CAS  PubMed  Google Scholar 

  27. Syrjänen K, Syrjänen S (2013) Detection of human papillomavirus in sinonasal papillomas: systemic review and meta-analysis. Laryngoscope. 123:181–192

    Article  PubMed  Google Scholar 

  28. Jenko K, Kocjan B, Zidar N et al (2011) In inverted papillomas HPV more likely represents incidental colonization than an etiological factor. Virchows Arch 459:529–538

    Article  PubMed  Google Scholar 

  29. Zhao RW, Guo ZQ, Zhang RX (2016) Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: a meta-analysis. J Clin Virol 79:36–43

    Article  PubMed  Google Scholar 

  30. Lin GC, Scheel A, Akkina S, Chinn S, Graham M, Komarck C et al (2013) MDP16, EGFR, Cyclin D1, and p53 staining patterns for inverted papilloma. Int Forum Allergy Rhinol 3:885–889

    Article  PubMed  PubMed Central  Google Scholar 

  31. Oncel S, Cosgul T, Calli A, Calli C, Pinar E (2011) Evaluation of p53, p63, p21, p27, ki-67 in paranasal sinus squamous cell carcinoma and inverted papilloma. Indian J Otolaryngol Head Neck Surg 63(2):172–177

    Article  PubMed  PubMed Central  Google Scholar 

  32. Saegusa M, Nitta H, Hashimura M, Okayasu I (1999) Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions. Histopathology 35(1):55–64

    Article  CAS  PubMed  Google Scholar 

  33. Yu H, Liu Q, Wang H, Wang D, Hu L, Sun X, Liu J (2014) The role of tissue factor pathway inhibitor-2 in malignant transformation of sinonasal inverted papilloma. Eur Arch Otorhinolaryngol 271(8):2191–2196

    Article  PubMed  Google Scholar 

  34. Re M, Zizzi A, Ferrante L, Stramazzotti D, Goteri G, Gioacchini FM, Olivieri F, Magliulo G, Rubini C (2014) p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival. Eur Arch Otorhinolaryngol 271(6):1641–1651

    Article  CAS  PubMed  Google Scholar 

  35. Gioacchini FM, Alicandri-Ciufelli M, Magliulo G, Rubini C, Presutti L, Re M (2015) The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 272(7):1569–1576

    Article  PubMed  Google Scholar 

  36. Tsou YA, Huang HJ, Wang TC, Tai CJ, Chen CM, Chen CY (2014) Evaluation of correlation of cell cycle proteins and Ki-67 interaction in paranasal sinus inverted papilloma prognosis and squamous cell carcinoma transformation. Biomed Res Int 2014:634945

    Article  PubMed  PubMed Central  Google Scholar 

  37. Stasikowska-Kanicka O, Wagrowska-Danilewicz M, Danilewicz M (2013) Immunohistochemical study on survivin in sinonasal tumors and its relationship with the immunoexpression of Ki67 and Bcl-2. Folia Histochem Cytobiol 51(3):225–231

    Article  PubMed  Google Scholar 

  38. Koo BS, Jung BJ, Kim SG, Liang ZL, Yeong MK, Rha KS (2011) Altered expression of E-cadherin and & #946:-catenin in malignant transformation of sinonasal inverted papillomas. Rhinology 49(4):479–485

    CAS  PubMed  Google Scholar 

  39. Wu HH, Zafar S, Huan Y, Yee H, Chiriboga L, Wang BY (2009) Fascin over expression is associated with dysplastic changes in sinonasal inverted papillomas: a study of 47 cases. Head Neck Pathol 3(3):212–216

    Article  PubMed  PubMed Central  Google Scholar 

  40. Huang CC, Lee TJ, Chang PH et al (2010) Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity. Laryngoscope 120:26–29

    Article  CAS  PubMed  Google Scholar 

  41. Liu W, Li Z, Luo Q et al (2011) The elevated expression of osteopontin and vascular endothelial growth factor in sinonasal inverted papilloma and its relationship with clinical severity. Am J Rhinol Allergy 25(5):313–317

    Article  CAS  PubMed  Google Scholar 

  42. Schrock A, Goke F, Wagner P, Bode M, Franzen A, Huss S, Agaimy A, Ihrler S, Kirsten R, Kristiansen G, Bootz F, Lengerke C, Perner S (2014) Fibroblast growth factor receptor-1 as a potential therapeutic target in sinonasal cancer. Head Neck 9:1253–1257

    Google Scholar 

  43. Udager AM, Rolland DC, McHugh JB, Betz BL, Murga-Zamalloa C, Carey TE, Marentette LJ, Hermsen MA, DuRoss KE, Lim MS, Elenitoba-Johnson KS, Brown NA (2015) High-frequency targetable EGFR mutations in sinonasal squamous cell carcinomas arising from inverted sinonasal papilloma. Cancer Res 75(13):2600–2606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  CAS  PubMed  Google Scholar 

  45. Strauss L, Bergmann C, Gooding W, Johnson JT, Whiteside TL (2007) The frequency and suppressor function of CD4+ CD25highFoxp3+T cells in the circulation of patients with squamous cell carcinoma of the head and neck. Clin Cancer Res Off J Am Assoc Cancer Res 13:6301–6311

    Article  CAS  Google Scholar 

  46. Gu Y, Wang C, Han D, Zhang L (2011) Increased frequencies of CD4+ CD25+ FOXP3+ regulatory T cells in human nasal inverted papilloma. Head Neck 33:1005–1012

    Article  PubMed  Google Scholar 

  47. Starska K, Brys M, Forma E, Olszewski J, Pietkiewicz P, Lewy-Trenda I, Stasikowska-Kanicka O, Danilewicz M, Krzeslak A (2015) Metallothionein 2° core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma). Tumor Biol 36:8559–8571

    Article  CAS  Google Scholar 

  48. Yamashita Y, Hasegawa M, Deng Z, Maeda H, Kondo S, Kyuna A, Matayoshi S, Agena S, Uehara T, Kouzaki H, Shimizu T, Ikegami T, Ganaha A, Suzuki M (2015) Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases. Infect Agent Cancer 4(10):23

    Article  Google Scholar 

  49. Norris HJ (1962) Papillary lesions of the nasal cavity and paranasal sinuses. I. Exophytic(squamous) papillomas. A study of 28 cases. Laryngoscope 72:1784–1797

    CAS  PubMed  Google Scholar 

  50. Norris HJ (1963) Papillary lesions of the nasal cavity and paranasal sinuses. II. Inverting papillomas. A study of 29 cases. Laryngoscope 73:1–17

    Article  CAS  PubMed  Google Scholar 

  51. Skolnik EM, Loewy A, Friedman JE (1966) Inverted papilloma of the nasal cavity. Arch Otolaryngol 84:61–67

    Article  CAS  PubMed  Google Scholar 

  52. Hyams VJ (1971) Papillomas of the nasal cavity and paranasal sinuses. A clinicopathological study of 315 cases. Ann Otol Rhinol Laryngol 80:192–206

    Article  CAS  PubMed  Google Scholar 

  53. Snyder RN, Perzin KH (1972) Papillomatosis of nasal cavity and paranasal sinuses (inverted papilloma, squamous papilloma). A clinicopathologic study. Cancer 30:668–690

    Article  CAS  PubMed  Google Scholar 

  54. Lasser A, Rothfeld PR, Shapiro RS (1976) Epithelial papilloma and squamous cell carcinoma of the nasal cavity and paranasal sinuses: a clinicopathological study. Cancer 38:2503–2510

    Article  CAS  PubMed  Google Scholar 

  55. Ridolfi RL, Lieberman PH, Erlandson RA, Moore OS (1977) Schneiderian papillomas: a clinicopathologic study of 30 cases. Am J Surg Pathol 1:43–53

    Article  CAS  PubMed  Google Scholar 

  56. Abildgaard-Jensen J, Greisen O (1985) Inverted papillomas of the nose and the paranasal sinuses. Clin Otolaryngol Allied Sci 10:135–143

    Article  CAS  PubMed  Google Scholar 

  57. KristensenS VorreP, ElbrondO SogaardH (1985) NasalSchneiderian papillomas: a study of 83 cases. Clin Otolaryngol Allied Sci 10:125–134

    Article  Google Scholar 

  58. Woodson GE, Robbins KT, Michaels L (1985) Inverted papilloma. Considerations in treatment. Arch Otolaryngol 111:806–811

    Article  CAS  PubMed  Google Scholar 

  59. Christensen WN, Smith RR (1986) Schneiderian papillomas: a clinicopathologic study of 67 cases. Hum Pathol 17:393–400

    Article  CAS  PubMed  Google Scholar 

  60. Segal K, Atar E, Mor C, Har-El G, Sidi J (1986) Inverting papilloma of the nose and paranasal sinuses. Laryngoscope 96:394–398

    Article  CAS  PubMed  Google Scholar 

  61. Weissler MC, Montgomery WW, Turner PA, Montgomery SK, Joseph MP (1986) Inverted papilloma. Ann Otol Rhinol Laryngol 95:215–221

    Article  CAS  PubMed  Google Scholar 

  62. Klemi PJ, Joensuu H, Siivonen L, Virolainen E, Syrjanen S, Syrjanen K (1989) Association of DNA aneuploidy with human papillomavirus-induced malignant transformation of sinonasal transitional papillomas. Otolaryngol Head Neck Surg 100:563–567

    CAS  PubMed  Google Scholar 

  63. Myers EN, Fernau JL, Johnson JT, Tabet JC, Barnes EL (1990) Management of inverted papilloma. Laryngoscope 100:481–490

    CAS  PubMed  Google Scholar 

  64. Furuta Y, Shinohara T, Sano K, Nagashima K, Inoue K, Tanaka K et al (1991) Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses. Laryngoscope 101:79–85

    Article  CAS  PubMed  Google Scholar 

  65. Outzen KE, Grontved A, Jorgensen K, Clausen PP (1991) Inverted papilloma of the nose and paranasal sinuses: a study of 67 patients. Clin Otolaryngol Allied Sci 16:309–312

    Article  CAS  PubMed  Google Scholar 

  66. DolginSR ZaveriVD, CasianoRR ManigliaAJ (1992) Different options for treatment of inverting papilloma of the nose and paranasal sinuses: a report of 41 cases. Laryngoscope 102:231–236

    Google Scholar 

  67. Bielamowicz S, Calcaterra TC, Watson D (1993) Inverting papilloma of the head and neck: the UCLA update. Otolaryngol Head Neck Surg 109:71–76

    Article  CAS  PubMed  Google Scholar 

  68. Kapadia SB, Barnes L, Pelzman K, Mirani N, Heffner DK, Bedetti C (1993) Carcinoma ex oncocytic Schneiderian (cylindrical cell) papilloma. Am J Otolaryngol 14:332–338

    Article  CAS  PubMed  Google Scholar 

  69. Vrabec DP (1994) The inverted Schneiderian papilloma: a 25-year study. Laryngoscope 104:582–605

    Article  CAS  PubMed  Google Scholar 

  70. Lawson W, Ho BT, Shaari CM, Biller HF (1995) Inverted papilloma: a report of 112 cases. Laryngoscope 105:282–288

    Article  CAS  PubMed  Google Scholar 

  71. Lesperance MM, Esclamado RM (1995) Squamous cell carcinoma arising in inverted papilloma. Laryngoscope 105:178–183

    Article  CAS  PubMed  Google Scholar 

  72. BuchwaldC FranzmannMB, JacobsenGK JuhlBR (1997) LindebergH. Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV). Rhinology 35:74–78

    Google Scholar 

  73. Nachtigal D, Yoskovitch A, Frenkiel S, Braverman I, Rochon L (1999) Unique characteristics of malignant Schneiderian papilloma. Otolaryngol Head Neck Surg 121:766–771

    Article  CAS  PubMed  Google Scholar 

  74. Kaufman MR, Brandwein MS, Lawson W (2002) Sinonasal papillomas: clinicopathologic review of 40 patients with inverted and oncocytic Schneiderian papillomas. Laryngoscope 112:1372–1377

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ENT Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ospedali Riuniti of Ancona, Via Conca 71, 60020, Ancona, Italy

    M. Re, F. M. Gioacchini, A. Bajraktari & A. Bertini

  2. Department of Diagnostic Medicine, Clinical and Public Health, University Hospital of Modena, Modena, Italy

    S. Kaleci

  3. Pathologic Anatomy and Histopathology Division, Department of Biomedical Sciences and Public Health, Polytechnic University of the Marches, Ancona, Italy

    C. Rubini

  4. Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy

    M. Tomasetti

  5. Department of Otorhinolaryngology, Audiology and Phoniatrics “G. Ferreri”University La Sapienza, Rome, Italy

    G. Magliulo

  6. ENT Metropolitan Unit, Bellaria Hospital, AUSL Bologna, Bologna, Italy

    E. Pasquini

Authors
  1. M. Re
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. M. Gioacchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Bajraktari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Tomasetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Kaleci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Rubini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Bertini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Magliulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Pasquini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. M. Gioacchini.

Ethics declarations

Conflict of interest

All the authors declare that there is no conflict of interest.

Financial disclosure

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Re, M., Gioacchini, F.M., Bajraktari, A. et al. Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review. Eur Arch Otorhinolaryngol 274, 2991–3000 (2017). https://doi.org/10.1007/s00405-017-4571-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-017-4571-2

Keywords

Search

Navigation