title: Use of human papillomavirus genotyping and biomarkers for targeted screening of anal dysplasia in human immunodeficiency virus-infected patients.
abstract: BACKGROUND
  Screening for anal dysplasia in human immunodeficiency virus (HIV)-infected patients is not standardized. High-resolution imaging is not adequate for mass screening, and anal cytology requires expertise. New biomarkers, selected because of their use in cervical cancer mass screening, have been originally tested for targeted and easy-to-perform screening.
  
  
  METHODS
  120 HIV-infected individuals (males 96.4%, mean age 47±11 years) were referred for clinical examination, anoscopy, and cytological studies on anal swab. Dysplasia grading, Human Papilloma Virus genotyping, E6/E7mRNA detection and p16(INK4A)/Ki-67 immunostaining were performed. High-grade lesions were histologically confirmed by anal biopsies after high-resolution anoscopy.
  
  
  RESULTS
  Among the 120 anal swabs analyzed, 36 (30%) had low grade and 6 (5%) had high-grade lesions. Virus genotype was identified in 88 patients (73.3%), and 77 (64.2%) were positive for high-risk genotype(s). High-risk genotype was associated to low-grade or high-grade lesions with a sensitivity of 0.93 and a specificity of 0.51. For E6/E7mRNA, sensitivity and specificity for low-grade and high-grade lesions were, respectively, 0.88 and 0.78. Combination of genotyping, E6/E7mRNA and p16(INK4A)/Ki-67 appropriately ruled out dysplasia in 55% of patients.
  
  
  CONCLUSIONS
  Three routine biomarkers may avoid unnecessary invasive procedures with the perspective of an improvement of patient compliance. A decision making algorithm, based on the combination of these three biomarkers, is proposed.
authors: Department of Virology, Pontchaillou University Hospital, Rennes, France; Université Rennes-I, Rennes, France.
authors: Clarisse
authors: C
authors: Dupin
authors: Université Rennes-I, Rennes, France; Gastroenterology Unit, Pontchaillou University Hospital, Rennes, France. Electronic address: laurent.siproudhis@chu-rennes.fr.
authors: Laurent
authors: L
authors: Siproudhis
authors: Université Rennes-I, Rennes, France; Department of Pathology, Pontchaillou University Hospital, Rennes, France.
authors: Sébastien
authors: S
authors: Henno
authors: Department of Virology, Pontchaillou University Hospital, Rennes, France; Université Rennes-I, Rennes, France.
authors: Sophie
authors: S
authors: Minjolle
authors: Université Rennes-I, Rennes, France; Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France.
authors: Cédric
authors: C
authors: Arvieux
authors: Université Rennes-I, Rennes, France; Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France.
authors: Pierre
authors: P
authors: Tattevin
mesh_terms: D000328:Adult; D001003:Anal Canal; D001004:Anus Diseases / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015415:Biomarkers / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D011351:Proctoscopy / Q000379:methods*; D012333:RNA, Messenger; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; C466080:E6 protein, human papillomavirus type 1; D019394:Ki-67 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger
keywords: Anal dysplasia; HIV; HPV; High-risk HPV E6/E7 mRNA; High-risk HPV genotypes; p16(INK4A)/Ki-67