title: Cytokeratin 7 in Oropharyngeal Squamous Cell Carcinoma: A Junctional Biomarker for Human Papillomavirus-Related Tumors.
abstract: Background:Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) represents a distinct subgroup of head and neck tumors. We analyze the expression of cytokeratin 7, a junctional biomarker with a SEQIKA fragment, which stabilizes HPV-16 E7 transcripts, in oropharyngeal SCCs.Methods:Archived tumor specimens and epidemiologic data were collected from patients with oropharyngeal SCCs over 10 years. Briefly, DNA was extracted from tissue blocks, and HPV testing was carried out using SPF10 HPV PCR and INNO-LiPA HPV Genotyping. Immunohistochemical staining for CK7 and p16ink4a was performed on the Ventana BenchMark Ultra Immunostainer. Analysis was by light microscopy using theH-score. CK7 expression was correlated with epidemiologic data, p16ink4a positivity, and HPV status using SPSS.Results:CK7 expression was observed specifically and uniformly in the tonsillar crypt epithelium of normal tonsils and tumor specimens. There were 226 cases of oropharyngeal SCCs, with 70 demonstrating both HPV and p16 positivity. Of 216 cases evaluated for CK7, 106 demonstrated some positivity, whereasH-score > 60 was seen in 55 of these. CK7H-score > 60 was significantly associated with tonsillar subsite and HPV and p16 positivity.Conclusions:An association between CK7 and HPV has been demonstrated. CK7-expressing tonsillar crypt cells potentially represent an oropharyngeal subsite susceptible to HPV-related SCC.Impact:Along with the cervix and anorectum, specific oropharyngeal expression of CK7 in a site predisposed to HPV-related tumors may suggest a role for CK7 in the pathogenesis of this subgroup of tumors. Further research is warranted to characterize the association between CK7 and HPV-related head and neck SCC.Cancer Epidemiol Biomarkers Prev; 26(5); 702-10. ©2017 AACR.
authors.affiliation: Department of Otolaryngology, St. James's Hospital, Dublin, Ireland. robbiewoods@rcsi.ie.|Department of Otolaryngology, Trinity College Dublin, Dublin, Ireland.|Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|Department of Otolaryngology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.
authors.forename: Robbie S R
authors.initials: RSR
authors.lastname: Woods
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.
authors.forename: Helen
authors.initials: H
authors.lastname: Keegan
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.
authors.forename: Christine
authors.initials: C
authors.lastname: White
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.
authors.forename: Prerna
authors.initials: P
authors.lastname: Tewari
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: Toner
authors.affiliation: Department of Histopathology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: Esther M
authors.initials: EM
authors.lastname: O'Regan
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.
authors.forename: Cara M
authors.initials: CM
authors.lastname: Martin
authors.affiliation: Department of Otolaryngology, St. James's Hospital, Dublin, Ireland.|Department of Otolaryngology, Trinity College Dublin, Dublin, Ireland.|Department of Otolaryngology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
authors.forename: Conrad V I
authors.initials: CVI
authors.lastname: Timon
authors.affiliation: Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin, Ireland.|CERVIVA Research Consortium, Ireland.|Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000821:virology*; D052162:Human papillomavirus 16; D006801:Humans; D053552:Keratin-7 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D053552:Keratin-7