title: FoxP3 overexpression and CD1a+ and CD3+ depletion in anal tissue as possible mechanisms for increased risk of human papillomavirus-related anal carcinoma in HIV infection.
abstract: OBJECTIVE
  We analysed local cellular and humoral immunity factors in the anal mucosa in an attempt to explain how HIV infection increases the risk of anal cancer in HPV-infected patients.
  
  
  METHODS
  HIV-positive cases and matched HIV-negative controls with more than one recurrence of condylomas were included in a prospective study following treatment of the initial lesions. Patients were followed every 3 to 6 months for the development of anal intraepithelial neoplasia (AIN3) and cancer for up to 60 months. Tissue CD1a(+), CD3(+), CD4(+), CD8(+) cells and mRNAs of selected cytokines and chemokines were quantified and compared in patients with or without AIN3 or cancer using morphometric or immunohistochemistry analysis and qRT-PCR.
  
  
  RESULTS
  Sixty-six individuals (22 patients and 44 controls) were included. In the case group, CD1a(+) and CD3(+) cell counts were significantly lower in biopsies from AIN3 and cancer specimens compared with those from AIN 1-2 or normal biopsies (P < 0.0001). A CD1a(+) count of < 10/mm was predictive of AIN3 and cancer (Odds ratio = 9.4, 95% CI: 5.4-18.3, P < 0.0001). IL-8 and IL23 levels were significantly higher in cancer than in non-cancer tissues regardless of HIV status (P = 0.02). FoxP3 expression was significantly higher in HIV-infected cases than in controls with AIN3/cancer (P < 0.04).
  
  
  CONCLUSIONS
  Depletion of CD1a(+) and CD3(+) cells and overexpression of FoxP3 in the anal mucosa appear likely to contribute to the risk of HPV-related anal cancer in HIV-infected patients. Furthermore, overexpression of IL-8 and IL-23 in the anal mucosa might be responsible for the development of this cancer regardless of HIV status.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Yaghoobi
authors.forename: S
authors.initials: S
authors.lastname: Le Gouvello
authors.forename: N
authors.initials: N
authors.lastname: Aloulou
authors.forename: C
authors.initials: C
authors.lastname: Duprez-Dutreuil
authors.forename: F
authors.initials: F
authors.lastname: Walker
authors.forename: I
authors.initials: I
authors.lastname: Sobhani
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000276:immunology / Q000378:metabolism*; D018949:Antigens, CD1; D001005:Anus Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002278:Carcinoma in Situ / Q000276:immunology / Q000821:virology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053759:Interleukin-23; D016209:Interleukin-8; D012333:RNA, Messenger