De Novo vs Inverted Papilloma–Associated Sinonasal Squamous Cell Carcinoma Survival Outcomes | Oncology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

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.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

References
1.
Dubal  PM , Bhojwani  A , Patel  TD ,  et al.  Squamous cell carcinoma of the maxillary sinus: a population-based analysis.   Laryngoscope. 2016;126(2):399-404. doi:10.1002/lary.25601 PubMedGoogle ScholarCrossref
2.
Sanghvi  S , Khan  MN , Patel  NR , Yeldandi  S , Baredes  S , Eloy  JA .  Epidemiology of sinonasal squamous cell carcinoma: a comprehensive analysis of 4994 patients.   Laryngoscope. 2014;124(1):76-83. doi:10.1002/lary.24264 PubMedGoogle ScholarCrossref
3.
Turner  JH , Reh  DD .  Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data.   Head Neck. 2012;34(6):877-885. doi:10.1002/hed.21830 PubMedGoogle ScholarCrossref
4.
Weber  AL , Stanton  AC .  Malignant tumors of the paranasal sinuses: radiologic, clinical, and histopathologic evaluation of 200 cases.   Head Neck Surg. 1984;6(3):761-776. doi:10.1002/hed.2890060310 PubMedGoogle ScholarCrossref
5.
Luce  D , Leclerc  A , Bégin  D ,  et al.  Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies.   Cancer Causes Control. 2002;13(2):147-157. doi:10.1023/A:1014350004255 PubMedGoogle ScholarCrossref
6.
Lobo  BCDA , D’Anza  B , Farlow  JL ,  et al.  Outcomes of sinonasal squamous cell carcinoma with and without association of inverted papilloma: a multi-institutional analysis.   Am J Rhinol Allergy. 2017;31(5):305-309. doi:10.2500/ajra.2017.31.4470 PubMedGoogle ScholarCrossref
7.
Ansa  B , Goodman  M , Ward  K ,  et al.  Paranasal sinus squamous cell carcinoma incidence and survival based on surveillance, epidemiology, and end results data, 1973 to 2009.   Cancer. 2013;119(14):2602-2610. doi:10.1002/cncr.28108 PubMedGoogle ScholarCrossref
8.
Chiu  AG , Jackman  AH , Antunes  MB , Feldman  MD , Palmer  JN .  Radiographic and histologic analysis of the bone underlying inverted papillomas.   Laryngoscope. 2006;116(9):1617-1620. doi:10.1097/01.mlg.0000230401.88711.e6 PubMedGoogle ScholarCrossref
9.
Hyams  VJ .  Papillomas of the nasal cavity and paranasal sinuses. A clinicopathological study of 315 cases.   Ann Otol Rhinol Laryngol. 1971;80(2):192-206. doi:10.1177/000348947108000205 PubMedGoogle ScholarCrossref
10.
Ringertz  N .  Pathology of malignant tumors arising in the nasal and paranasal cavities and maxilla.   Acta Otolaryngol. 1938;27:31–42.Google Scholar
11.
Snyder  RN , Perzin  KH .  Papillomatosis of nasal cavity and paranasal sinuses (inverted papilloma, squamous papilloma). a clinicopathologic study.   Cancer. 1972;30(3):668-690. doi:10.1002/1097-0142(197209)30:3<668::AID-CNCR2820300315>3.0.CO;2-B PubMedGoogle ScholarCrossref
12.
Suh  KW , Facer  GW , Devine  KD , Weiland  LH , Zujko  RD .  Inverting papilloma of the nose and paranasal sinuses.   Laryngoscope. 1977;87(1):35-46. doi:10.1288/00005537-197701000-00005 PubMedGoogle ScholarCrossref
13.
Christensen  WN , Smith  RR .  Schneiderian papillomas: a clinicopathologic study of 67 cases.   Hum Pathol. 1986;17(4):393-400. doi:10.1016/S0046-8177(86)80463-4 PubMedGoogle ScholarCrossref
14.
Mirza  S , Bradley  PJ , Acharya  A , Stacey  M , Jones  NS .  Sinonasal inverted papillomas: recurrence, and synchronous and metachronous malignancy.   J Laryngol Otol. 2007;121(9):857-864. doi:10.1017/S002221510700624X PubMedGoogle ScholarCrossref
15.
Nygren  A , Kiss  K , von Buchwald  C , Bilde  A .  Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998-2008.   Acta Otolaryngol. 2016;136(3):333-336. doi:10.3109/00016489.2015.1116123 PubMedGoogle ScholarCrossref
16.
Lawson  W , Patel  ZM .  The evolution of management for inverted papilloma: an analysis of 200 cases.   Otolaryngol Head Neck Surg. 2009;140(3):330-335. doi:10.1016/j.otohns.2008.11.010 PubMedGoogle ScholarCrossref
17.
de Almeida  JRS , Su  SY , Koutourousiou  M ,  et al.  Endonasal endoscopic surgery for squamous cell carcinoma of the sinonasal cavities and skull base: oncologic outcomes based on treatment strategy and tumor etiology.   Head Neck. 2015;37(8):1163-1169. doi:10.1002/hed.23731 PubMedGoogle ScholarCrossref
18.
Lavertu  P , Roberts  JK , Kraus  DH ,  et al.  Squamous cell carcinoma of the paranasal sinuses: the Cleveland Clinic experience 1977-1986.   Laryngoscope. 1989;99(11):1130-1136. doi:10.1288/00005537-198911000-00005 PubMedGoogle ScholarCrossref
19.
Yan  CHN , Newman  JG , Kennedy  DW , Palmer  JN , Adappa  ND .  Clinical outcomes of sinonasal squamous cell carcinomas based on tumor etiology.   Int Forum Allergy Rhinol. 2017;7(5):508-513. doi:10.1002/alr.21899 PubMedGoogle ScholarCrossref
20.
Yu  MS , Lim  WS , Lee  BJ , Chung  YS .  Squamous cell carcinoma associated with inverted papilloma of the maxillary sinus: our experience with 21 patients.   Clin Otolaryngol. 2017;42(5):1048-1052. doi:10.1111/coa.12804PubMedGoogle ScholarCrossref
21.
Stroup  DF , Berlin  JA , Morton  SC ,  et al.  Meta-analysis of observational studies in epidemiology: a proposal for reporting.   JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008 PubMedGoogle ScholarCrossref
22.
Drewry  AM , Ablordeppey  EA , Murray  ET ,  et al.  Antipyretic therapy in critically ill septic patients: a systematic review and meta-analysis.   Crit Care Med. 2017;45(5):806-813. doi:10.1097/CCM.0000000000002285 PubMedGoogle ScholarCrossref
23.
Slim  K , Nini  E , Forestier  D , Kwiatkowski  F , Panis  Y , Chipponi  J .  Methodological index for non-randomized studies (minors): development and validation of a new instrument.   ANZ J Surg. 2003;73(9):712-716. doi:10.1046/j.1445-2197.2003.02748.x PubMedGoogle ScholarCrossref
24.
Tierney  JF , Stewart  LA , Ghersi  D , Burdett  S , Sydes  MR .  Practical methods for incorporating summary time-to-event data into meta-analysis.   Trials. 2007;8:16. doi:10.1186/1745-6215-8-16 PubMedGoogle ScholarCrossref
25.
Buiret  G , Montbarbon  X , Fleury  B ,  et al.  Inverted papilloma with associated carcinoma of the nasal cavity and paranasal sinuses: treatment outcomes.   Acta Otolaryngol. 2012;132(1):80-85. doi:10.3109/00016489.2011.620001 PubMedGoogle ScholarCrossref
26.
Choi  JW , Kim  SG , Kim  YM , Yoon  YH , Kim  AY , Rha  KS .  Clinical and histologic features of inverted papilloma-associated malignancy.   Eur Arch Otorhinolaryngol. 2012;269(11):2349-2354. doi:10.1007/s00405-012-1935-5PubMedGoogle ScholarCrossref
27.
Chowdhury  N , Alvi  S , Kimura  K ,  et al.  Outcomes of HPV-related nasal squamous cell carcinoma.   Laryngoscope. 2017;127(7):1600-1603. doi:10.1002/lary.26477 PubMedGoogle ScholarCrossref
28.
Dulguerov  P , Jacobsen  MS , Allal  AS , Lehmann  W , Calcaterra  T .  Nasal and paranasal sinus carcinoma: are we making progress? a series of 220 patients and a systematic review.   Cancer. 2001;92(12):3012-3029. doi:10.1002/1097-0142(20011215)92:12<3012::AID-CNCR10131>3.0.CO;2-E PubMedGoogle ScholarCrossref
29.
Ganly  I , Patel  SG , Singh  B ,  et al.  Craniofacial resection for malignant paranasal sinus tumors: report of an international collaborative study.   Head Neck. 2005;27(7):575-584. doi:10.1002/hed.20165 PubMedGoogle ScholarCrossref
30.
Haraguchi  H , S Ebihara, M Saikawa, K Mashima, T Haneda, K Hirano. Malignant tumors of the nasal cavity: review of a 60-case series.  Jpn J Clin Oncol. 1995;25(5):188-94.
31.
Hong  S-LK , Kim  BH , Lee  JH , Cho  KS , Roh  HJ .  Smoking and malignancy in sinonasal inverted papilloma.   Laryngoscope. 2013;123(5):1087-1091. doi:10.1002/lary.23876 PubMedGoogle ScholarCrossref
32.
Hug  EBW , Wang  CC , Montgomery  WW , Goodman  ML .  Management of inverted papilloma of the nasal cavity and paranasal sinuses: importance of radiation therapy.   Int J Radiat Oncol Biol Phys. 1993;26(1):67-72. doi:10.1016/0360-3016(93)90174-T PubMedGoogle ScholarCrossref
33.
Karligkiotis  A , Lepera  D , Volpi  L ,  et al.  Survival outcomes after endoscopic resection for sinonasal squamous cell carcinoma arising on inverted papilloma.   Head Neck. 2016;38(11):1604-1614. doi:10.1002/hed.24481 PubMedGoogle ScholarCrossref
34.
Kim  K , Kim  D , Koo  Y ,  et al.  Sinonasal carcinoma associated with inverted papilloma: a report of 16 cases.   J Craniomaxillofac Surg. 2012;40(4):e125-e129. doi:10.1016/j.jcms.2011.07.007PubMedGoogle ScholarCrossref
35.
Lee  CH , Hur  DG , Roh  HJ ,  et al.  Survival rates of sinonasal squamous cell carcinoma with the new AJCC staging system.   Arch Otolaryngol Head Neck Surg. 2007;133(2):131-134. doi:10.1001/archotol.133.2.131 PubMedGoogle ScholarCrossref
36.
Lesperance  MME , Esclamado  RM .  Squamous cell carcinoma arising in inverted papilloma.   Laryngoscope. 1995;105(2):178-183. doi:10.1288/00005537-199502000-00013 PubMedGoogle ScholarCrossref
37.
Li  W , Lu  H , Zhang  H , Sun  X , Hu  L , Wang  D .  Squamous cell carcinoma associated with inverted papilloma: Recurrence and prognostic factors.   Oncol Lett. 2020;19(1):1082-1088.PubMedGoogle Scholar
38.
Li  Y , Wang  C , Wang  R ,  et al.  Survival outcomes and prognostic factors of squamous cell carcinomas arising from sinonasal inverted papillomas: a retrospective analysis of 120 patients.   Int Forum Allergy Rhinol. 2019;9(11):1367-1373. doi:10.1002/alr.22400 PubMedGoogle ScholarCrossref
39.
Liang  Q-ZL , Li  DZ , Wang  XL , Huang  H , Xu  ZG , Wu  YH .  Survival outcome of squamous cell carcinoma arising from sinonasal inverted papilloma.   Chin Med J (Engl). 2015;128(18):2457-2461. doi:10.4103/0366-6999.164929 PubMedGoogle ScholarCrossref
40.
McKay  SP , Shibuya  TY , Armstrong  WB ,  et al.  Cell carcinoma of the paranasal sinuses and skull base.   Am J Otolaryngol. 2007;28(5):294-301. doi:10.1016/j.amjoto.2006.09.007 PubMedGoogle ScholarCrossref
41.
Mine  S , Saeki  N , Horiguchi  K , Hanazawa  T , Okamoto  Y .  Craniofacial Resection for Sinonasal Malignant Tumors: Statistical Analysis of Surgical Outcome over 17 Years at a Single Institution.   Skull Base. 2011;21(4):243-248. doi:10.1055/s-0031-1280686PubMedGoogle ScholarCrossref
42.
Nicolai  P , Battaglia  P , Bignami  M ,  et al.  Endoscopic surgery for malignant tumors of the sinonasal tract and adjacent skull base: a 10-year experience.   Am J Rhinol. 2008;22(3):308-316. doi:10.2500/ajr.2008.22.3170 PubMedGoogle ScholarCrossref
43.
Nudell  J , Chiosea  S , Thompson  LD .  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. 2014;8(3):269-286. doi:10.1007/s12105-014-0527-7 PubMedGoogle ScholarCrossref
44.
Russo  AL , Adams  JA , Weyman  EA ,  et al.  Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma.   Int J Radiat Oncol Biol Phys. 2016;95(1):368-376. doi:10.1016/j.ijrobp.2016.02.042PubMedGoogle ScholarCrossref
45.
Yasumatsu  R , Nakashima  T , Sato  M ,  et al.  Clinical management of squamous cell carcinoma associated with sinonasal inverted papilloma.   Auris Nasus Larynx. 2017;44(1):98-103. doi:10.1016/j.anl.2016.04.004 PubMedGoogle ScholarCrossref
46.
Yu  H-XL , Liu  G .  Malignant transformation of sinonasal inverted papilloma: a retrospective analysis of 32 cases.   Oncol Lett. 2014;8(6):2637-2641. doi:10.3892/ol.2014.2539 PubMedGoogle ScholarCrossref
47.
Mirza  S , Bradley  PJ , Acharya  A , Stacey  M , Jones  NS .  Sinonasal inverted papillomas: recurrence, and synchronous and metachronous malignancy.   J Laryngol Otol. 2007;121(9):857-864. doi:10.1017/S002221510700624X PubMedGoogle ScholarCrossref
48.
Tanvetyanon  T , Qin  D , Padhya  T , Kapoor  R , McCaffrey  J , Trotti  A .  Survival outcomes of squamous cell carcinoma arising from sinonasal inverted papilloma: report of 6 cases with systematic review and pooled analysis.   Am J Otolaryngol. 2009;30(1):38-43. doi:10.1016/j.amjoto.2008.02.005 PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close