Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Eur J Obstet Gynecol Reprod Biol. 2008 Nov;141(1):70-4. doi: 10.1016/j.ejogrb.2008.06.010. Epub 2008 Aug 9.

Abstract

Objectives: 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.

Study design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • HLA Antigens / metabolism*
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / metabolism*
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / physiopathology*
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • HLA Antigens
  • Histocompatibility Antigens Class I