title: Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany.
abstract: The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Elgar Susanne
authors.initials: ES
authors.lastname: Quabius
authors.affiliation: Institute for Pathology, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Haag
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Kühnel
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Henry
authors.affiliation: Department of Otorhinolaryngology, University of Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Hoffmann
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Görögh
authors.affiliation: Institute for Medical Informatics and Statistics, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hedderich
authors.affiliation: Institute for Pathology, Ernst-Moritz-Arndt-University of Greifswald, D-17487 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, D-17475 Greifswald, Germany.
authors.forename: Achim G
authors.initials: AG
authors.lastname: Beule
authors.affiliation: Department of Otorhinolaryngology, Hospitals of the City of Cologne, Cologne, D-51067 Köln, 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, D-20246 Hamburg, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Rostock, D-18057 Rostock, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Óvári
authors.affiliation: Department of Otorhinolaryngology, Medical University of Hannover, D-30625 Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Durisin
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Klinikum Oldenburg, D-26133 Oldenburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hoppe
authors.affiliation: Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Tribius
authors.affiliation: Institute for Pathology, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ambrosch
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D005260:Female; D014644:Genetic Variation; D005843:Geography; D005858:Germany / Q000453:epidemiology; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology*; D015995:Prevalence; D000077195:Squamous Cell Carcinoma of Head and Neck