title: The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma.
abstract: Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.
authors.affiliation: Deptartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University of Kiel, Germany; Institute of Immunology, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Elgar S
authors.initials: ES
authors.lastname: Quabius
authors.affiliation: Deptartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Görögh
authors.affiliation: Deptartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Gerrit S
authors.initials: GS
authors.lastname: Fischer
authors.affiliation: Department of Otorhinolaryngology, University of Schleswig-Holstein, Lübeck, Germany.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Hoffmann
authors.affiliation: Institute of Pathology, University of Schleswig-Holstein, Lübeck, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gebhard
authors.affiliation: Institute for Pathology, Ernst-Moritz-Arndt-University of Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Evert
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt-University of Greifswald, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Beule
authors.affiliation: Department of Otorhinolaryngology, Hospitals of the City of Cologne, Cologne, University of Witten/Herdecke, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Maune
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Medical Centre Hamburg-Eppendorf, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Rostock, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Óvári
authors.affiliation: Department of Otorhinolaryngology, Medical University of Hanover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Durisin
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Klinikum Oldenburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hoppe
authors.affiliation: Institute for Pathology, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Institute for Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, Germany The presented joint venture is part of The Human Papillomavirus Infection and Oropharyngeal Cancer Consortium (HOCC) Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hedderich
authors.affiliation: Deptartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ambrosch
authors.affiliation: Deptartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University of Kiel, Germany. Electronic address: mhoffmann@hno.uni-kiel.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000254:growth & development*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000517:prevention & control*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor
keywords: Annexin A2; HNSCC; HPV; SLPI