title: 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.
abstract: 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 p16(INK4a) 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.
authors.affiliation: The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. lacoj@lfhk.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Laco
authors.affiliation: The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Sieglová
authors.affiliation: The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Vošmiková
authors.affiliation: Department of Pathology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dundr
authors.affiliation: Department of Pathology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Němejcová
authors.affiliation: Department of Clinical and Molecular Pathology, Palacky University Olomouc, Faculty of Medicine and Dentistry and University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Michálek
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Čelakovský
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Chrobok
authors.affiliation: Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Radovan
authors.initials: R
authors.lastname: Mottl
authors.affiliation: Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Mottlová
authors.affiliation: Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Luboš
authors.initials: L
authors.lastname: Tuček
authors.affiliation: Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Radovan
authors.initials: R
authors.lastname: Slezák
authors.affiliation: Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Chmelařová
authors.affiliation: Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Sirák
authors.affiliation: Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Vošmik
authors.affiliation: The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Ryška
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000302:isolation & purification*; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D010255:Paranasal Sinus Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis*; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014158:Transcription, Genetic
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Human papillomavirus (HPV); Nonkeratinizing; RNA; Sinonasal carcinoma; Squamous cell carcinoma; p16 protein