title: Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients' prognosis.
abstract: Integration, which leads to the disruption of the circular HPV genome, is considered as a critical, albeit not obligatory, step in carcinogenic progression. Although cervical carcinomas with extrachromosomal HPV plasmid genomes have been described, the virus is integrated in 70% of HPV16-positive cervical tumours. Limited information is available about HPV integration in head and neck tumours (HNC). In this study, we have characterised the physical status of HPV in a set of tonsillar tumour samples using different methods--the mapping of E2 integration breakpoint at the mRNA level, the 3' RACE based Amplification of Papillomavirus Oncogene Transcripts (APOT) assay and Southern blot. Furthermore, the impact of HPV integration on patients' prognosis has been evaluated in a larger set of 186 patients with head and neck cancer. Based on the analysis of E2 mRNA, HPV was integrated in the host genome in 43% of the HPV-positive samples. Extrachromosomal or mixed form was present in 57%. In fresh frozen samples, the APOT and E2 mapping results were in agreement. The results were confirmed using Southern blotting. Furthermore, the type and exact site of integration were determined. The survival analysis of 186 patients revealed HPV positivity, tumour size and lymph node positivity as factors that influence disease specific survival. However, no statistically significant difference was found in disease specific survival between patients with HPV-positive integrated vs. extrachromosomal/mixed forms of the virus.
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vojtechova
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabol
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Salakova
authors.affiliation: Veterans Affairs Healthcare System and Department of Pathology, University of Iowa, Iowa City, IA.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Turek
authors.affiliation: Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Grega
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Smahelova
authors.affiliation: Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science of the Palacky University in Olomouc, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Vencalek
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Lukesova
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Klozar
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Czech Republic.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tachezy
mesh_terms: D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000821:virology*; D006801:Humans; D008297:Male; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D011379:Prognosis; D016016:Proportional Hazards Models; D000077195:Squamous Cell Carcinoma of Head and Neck; D014067:Tonsillar Neoplasms / Q000821:virology*; D016662:Virus Integration / Q000235:genetics*
keywords: HPV; head and neck tumours; integration; prognosis; survival