title: HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
abstract: OBJECTIVE
  To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy.
  
  
  METHODS
  For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival.
  
  
  RESULTS
  In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases.
  
  
  CONCLUSIONS
  HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Lohaus
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Linge
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Berlin, Germany; Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Tinhofer
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Berlin, Germany; Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Essen, Germany; Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Eleni
authors.initials: E
authors.lastname: Gkika
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Essen, Germany; Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
authors.affiliation: Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Balermpas
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Frankfurt, Germany; Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Freiburg, Germany; Department of Radiation Oncology, Clinical Study Section, University of Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Avlar
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Freiburg, Germany; Department of Radiation Oncology, University of Freiburg, Germany.
authors.forename: Anca-Ligia
authors.initials: AL
authors.lastname: Grosu
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Heidelberg, Germany; Department of Radiation Oncology, Heidelberg Ion Therapy Center (HIT), Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Abdollahi
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Heidelberg, Germany; Department of Radiation Oncology, Heidelberg Ion Therapy Center (HIT), Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany; Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Bayer
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany; Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany; Department of Radiation Oncology, Technische Universität München, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Pigorsch
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany; Department of Radiation Oncology, Technische Universität München, Germany.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Tübingen, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Mönnich
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Tübingen, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Cläre
authors.initials: C
authors.lastname: von Neubeck
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Tumor- and Normal Tissue Bank, Universitäts KrebsCentrum (UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Baretton
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Löck
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Institute of Radiooncology, Helmholtz-Zentrum Dresden - Rossendorf, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Institute of Radiooncology, Helmholtz-Zentrum Dresden - Rossendorf, Germany. Electronic address: Michael.Baumann@uniklinikum-dresden.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA
keywords: DKTK-ROG; HNSCC; HPV; Postoperative radiochemotherapy; p16; p53