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)

Fabian Lohaus; Annett Linge; Inge Tinhofer; Volker Budach; Eleni Gkika; Martin Stuschke; Panagiotis Balermpas; Claus Rödel; Melanie Avlar; Anca-Ligia Grosu; Amir Abdollahi; Jürgen Debus; Christine Bayer; Claus Belka; Steffi Pigorsch; Stephanie E Combs; David Mönnich; Daniel Zips; Cläre von Neubeck; Gustavo B Baretton; Steffen Löck; Howard D Thames; Mechthild Krause; Michael Baumann; DKTK-ROG

doi:10.1016/j.radonc.2014.11.011

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)

Radiother Oncol. 2014 Dec;113(3):317-23. doi: 10.1016/j.radonc.2014.11.011. Epub 2014 Dec 2.

Authors

Fabian Lohaus¹, Annett Linge¹, Inge Tinhofer², Volker Budach², Eleni Gkika³, Martin Stuschke³, Panagiotis Balermpas⁴, Claus Rödel⁵, Melanie Avlar⁶, Anca-Ligia Grosu⁷, Amir Abdollahi⁸, Jürgen Debus⁹, Christine Bayer¹⁰, Claus Belka¹¹, Steffi Pigorsch¹², Stephanie E Combs¹², David Mönnich¹³, Daniel Zips¹³, Cläre von Neubeck¹⁴, Gustavo B Baretton¹⁵, Steffen Löck¹⁶, Howard D Thames¹⁷, Mechthild Krause¹⁸, Michael Baumann¹⁹; DKTK-ROG

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
⁵ 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.
⁶ 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.
⁷ German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Freiburg, Germany; Department of Radiation Oncology, University of Freiburg, Germany.
⁸ 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.
⁹ 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.
¹⁰ German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany.
¹¹ 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.
¹² German Cancer Research Center (DKFZ), Heidelberg, Germany and German Cancer Consortium (DKTK) partner sites: Munich, Germany; Department of Radiation Oncology, Technische Universität München, Germany.
¹³ 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.
¹⁴ 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.
¹⁵ 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.
¹⁶ OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁷ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
¹⁸ 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.
¹⁹ 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: [email protected].

PMID: 25480095
DOI: 10.1016/j.radonc.2014.11.011

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.

Materials and 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.

Keywords: DKTK-ROG; HNSCC; HPV; Postoperative radiochemotherapy; p16; p53.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / therapy*
Carcinoma, Squamous Cell / virology
Chemoradiotherapy / methods
Cyclin-Dependent Kinase Inhibitor p16 / genetics*
DNA / genetics
Female
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / therapy*
Head and Neck Neoplasms / virology
Humans
Male
Oropharyngeal Neoplasms / genetics*
Oropharyngeal Neoplasms / therapy*
Oropharyngeal Neoplasms / virology
Papillomaviridae / genetics
Postoperative Period
Prognosis
Prospective Studies
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck
Survival Analysis
Treatment Outcome

Substances

Cyclin-Dependent Kinase Inhibitor p16
DNA