title: Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal.
abstract: OBJECTIVE
  Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease-specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal.
  
  
  METHODS
  HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone.
  
  
  RESULTS
  HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved OS (74% v 52%; P=.036) and DSS (84% v 52%; P=.002), and p16 positivity was significantly correlated with improved OS (76% v 30%; P<.001) and DSS (85% v 30%; P<.001). In multivariable COX analysis that included HPV status, p16 status, sex, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for OS (hazard ratio [HR], 0.07; 95% CI, 0.01 to 0.61; P=.016) and DSS (HR, 0.07; 95% CI, 0.01 to 0.53; P=.011).
  
  
  CONCLUSIONS
  p16 positivity is an independent prognostic factor for OS and DSS in patients with AJCC stages I to III carcinoma of the anal canal.
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark. eva.serup-hansen@regionh.dk.
authors.forename: Eva
authors.initials: E
authors.lastname: Serup-Hansen
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Linnemann
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Skovrider-Ruminski
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Poul Flemming
authors.initials: PF
authors.lastname: Geertsen
authors.affiliation: All authors: Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Havsteen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy / Q000821:virology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D019942:Genes, p16; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins