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

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 ( χ 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.