title: High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas.
abstract: It has been reported that high-risk human papillomavirus (HPV) is a causative agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of the transcriptionally active HPV has been proved through the identification of HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess the HPV-active transcription in a series of sinonasal carcinomas, in correlation with the HPV DNA identification and the p16 immunohistochemistry. Seventy patients with squamous cell carcinomas of the sinonasal tract were included in the survey. The main clinicopathological characteristics were recorded. All tumors were investigated for HPV through the HPV DNA detection by PCR, using the SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases. Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and one HPV35. In situ hybridization showed a dotted nuclear positivity in all these cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong, diffuse positivity for p16 was observed only in the HPV-positive cases. The 14 HPV-positive squamous cell carcinomas were non-keratinizing or scarcely keratinizing tumors. No significant differences were found in terms of gender, age, or staging at diagnosis between HPV-positive and HPV-negative tumors. However, differences in disease-free survival and overall survival between both groups of patients were significant (P=0.004 and P=0.028, respectively). In conclusion, we have shown that HPV is the etiological agent of a subset of sinonasal carcinomas demonstrating the transcriptionally active HPV in these tumors. Immunostaining for p16 can be used as a surrogate marker to identify these tumors.
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Larque
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Hakim
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Nadal
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Department of Gynecology, Obstetrics and Neonatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: del Pino
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Marimon
authors.affiliation: Department of Otolaryngology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Isam
authors.initials: I
authors.lastname: Alobid
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cardesa
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Llucia
authors.initials: L
authors.lastname: Alos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000096:biosynthesis*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D050725:Papillomavirus E7 Proteins / Q000032:analysis; D030361:Papillomavirus Infections / Q000150:complications* / Q000401:mortality; D010255:Paranasal Sinus Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16