title: Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer.
abstract: OBJECTIVE
  Viruses and tumour cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type.
  
  
  METHODS
  Cervical biopsies (N=74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n=31), CIN2-3 (n=19), and invasive cancer (n=14) were evaluated alongside 10 normal cervical specimens.
  
  
  RESULTS
  HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR=0.12, 95%CI: 0.0163-0.7899; p=0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend=4.01; p=0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR=11.25, 95%CI: 2.324-54.465; p=0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67).
  
  
  CONCLUSIONS
  HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection.
authors.affiliation: Division of Clinical Immunology, University of São Paulo, Ribeirão Preto, Brazil. epigin@uol.com.br
authors.forename: Maria Alice G
authors.initials: MA
authors.lastname: Gonçalves
authors.forename: Magali
authors.initials: M
authors.lastname: Le Discorde
authors.forename: Renata T
authors.initials: RT
authors.lastname: Simões
authors.forename: Michele
authors.initials: M
authors.lastname: Rabreau
authors.forename: Edson G
authors.initials: EG
authors.lastname: Soares
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
mesh_terms: D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D030361:Papillomavirus Infections / Q000473:pathology / Q000503:physiopathology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000097625:HLA-E Antigens
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens