title: Human papillomavirus-related carcinomas of the sinonasal tract.
abstract: High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. jbishop@jhmi.edu
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.forename: Theresa W
authors.initials: TW
authors.lastname: Guo
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Takenori
authors.initials: T
authors.lastname: Ogawa
authors.forename: Sara I
authors.initials: SI
authors.lastname: Pai
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015897:Comorbidity; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010255:Paranasal Sinus Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral