title: Performance of p16INK4a immunocytochemistry as a marker of anal squamous intraepithelial lesions.
abstract: BACKGROUND
  Protein p16(INK4a) immunocytochemistry (ICCp16) has the potential to reveal lesions at risk of progression to anal cancer. This study examined measures of diagnostic validity of ICCp16 in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas in the coloproctology outpatient clinic.
  
  
  METHODS
  One hundred ninety HIV-positive patients were consecutively enrolled in 2007 and 2008. All patients underwent anal cytologic sampling to perform ICCp16 in conventional and GluCyte (Synermed International, Westfield, Indiana and S¸ao Paulo, Brazil) smears and also for genotyping of human papillomavirus (HPV). Patients were then subjected to anal biopsies monitored by high-resolution anoscopy. Hematoxylin-eosin and immunoperoxidase p16 (clone 6H12) stains were performed in slides with biopsied and cytological specimens, respectively. HPV genotyping on anal scrapings was performed by a polymerase-chain reaction (PCR)-based method. The immunochemical findings were compared with histopathological and PCR results in contingency tables and analyzed by nonparametric tests. Measures of diagnostic validity of ICCp16 were calculated. Statistical significance was set at P ≤ .5.
  
  
  RESULTS
  There was no statistically significant association between the immunochemical results (conventional or GluCyte smears) and histopathological or HPV genotyping findings (P > .05). In the best scenario, ICCp16 presented 31% sensitivity and 81% specificity for the diagnosis of anal squamous intraepithelial lesion (ASIL) and 30% and 66%, respectively, for the diagnosis of infection with high-risk HPV.
  
  
  CONCLUSIONS
  There was no association between ICCp16 results and histopathological findings nor between ICCp16 and HPV genotyping. ICCp16 showed poor sensitivity and moderate specificity for the diagnosis of ASIL or high-risk HPV.
authors.affiliation: Postgraduation Program of Tropical Medicine Foundation of Amazonas / University of the State of Amazonas, Manaus, Brazil, Department of Surgery, School of Medicine, Federal University of Amazonas, Manaus, Brazil. itramujas@ufam.edu.br
authors.forename: Ivan
authors.initials: I
authors.lastname: Tramujas da Costa E Silva
authors.forename: Michelle
authors.initials: M
authors.lastname: Coelho Ribeiro
authors.forename: Felicidad
authors.initials: F
authors.lastname: Santos Gimenez
authors.forename: Junia Raquel
authors.initials: JR
authors.lastname: Dutra Ferreira
authors.forename: Renata Silva
authors.initials: RS
authors.lastname: Galvao
authors.forename: Paula Emanuelle
authors.initials: PE
authors.lastname: Vasco Hargreaves
authors.forename: Adriana
authors.initials: A
authors.lastname: Gonçalves Daumas Pinheiro Guimaraes
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: de Lima Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis*; D013048:Specimen Handling; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16