The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16INK4a protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23–83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1–241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.
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The authors are very grateful to Professor Ivo Šteiner, MD, PhD, and to Folakemi A. Sobande, MD, PhD, for English language correction.
The experiments carried out in this study comply with the current laws of the Czech Republic.
This study is based on the experiments conducted by one of the co-authors, Kateřina Sieglová, during her undergraduate studies for Master degree at the Charles University in Prague, Faculty of Pharmacy in Hradec Kralove. The study was supported by the programs PRVOUK P37/11 and PRVOUK P27/LF1/1 and by the project BBMRI LM2010004. The funding sources had no involvement on the study design, collection, analysis, and interpretation of data, on the writing of the report, and on the decision to submit the article for publication.
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The authors declare that they have no conflict of interest.
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Laco, J., Sieglová, K., Vošmiková, H. et al. The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis. Virchows Arch 467, 405–415 (2015). https://doi.org/10.1007/s00428-015-1812-x
- Sinonasal carcinoma
- Squamous cell carcinoma
- Human papillomavirus (HPV)
- p16 protein