title: Influence of human papillomavirus and p16(INK4a) on treatment outcome of patients with anal cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate HPV-DNA and p16(INK4a) (p16) expression as prognostic markers for outcome in patients with anal cancer.
  
  
  METHODS
  From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.
  
  
  RESULTS
  Median follow-up was 48.6months (range 2.8-169.1months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p=0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p<0.001] and improved local control [81.0% vs. 55.9%, p=0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p=0.015] and PFS [p=0.002] for cHPPAC.
  
  
  CONCLUSIONS
  The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: Stefan.Koerber@med.uni-heidelberg.de.
authors.forename: Stefan Alexander
authors.initials: SA
authors.lastname: Koerber
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: clara.schoneweg@t-online.de.
authors.forename: Clara
authors.initials: C
authors.lastname: Schoneweg
authors.affiliation: Institute of Biostatistics, German Cancer Research Center, Heidelberg, Germany. Electronic address: a.slynko@dkfz-heidelberg.de.
authors.forename: Alla
authors.initials: A
authors.lastname: Slynko
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: David.Krug@med.uni-heidelberg.de.
authors.forename: David
authors.initials: D
authors.lastname: Krug
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: Matthias.Haefner@med.uni-heidelberg.de.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Haefner
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: Klaus.Herfarth@med.uni-heidelberg.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Herfarth
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: Juergen.Debus@med.uni-heidelberg.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg, Germany. Electronic address: Florian.Sterzing@med.uni-heidelberg.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Sterzing
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany. Electronic address: knebel@med.uni-heidelberg.de.
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany. Electronic address: elena.prigge@med.uni-heidelberg.de.
authors.forename: Elena-Sophie
authors.initials: ES
authors.lastname: Prigge
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany. Electronic address: miriam.reuschenbach@med.uni-heidelberg.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Reuschenbach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Anal [canal] cancer; HPV; Human papillomavirus; [Chemo] radiation; p16