HLA class II antigens normally are expressed by professional antigen-presenting cells, but are also reported to be expressed by several tumors of non-lymphoid origin. Strong HLA class II antigen expression has been described for a subset of HPV-associated cervical cancers. We characterized HLA class II antigen expression during HPV-induced cervical tumor development by examining the expression in CIN lesions and cervical cancers and correlated the results with immune cell infiltration.
FFPE tissue sections of CIN1, CIN2, CIN3 and invasive SCC patients (n=103 in total) were analyzed by immunohistochemical staining with monoclonal antibodies specific for HLA class II antigens (LGII-612.14) and for different T cell markers (CD3, CD8, Foxp3, Granzyme B, CD3 zeta-chain).
HLA class II antigen expression was absent in all samples of normal, non-neoplastic squamous epithelium adjacent to lesions (n=29). However, a strong and uniform staining pattern was found in the columnar epithelium and squamocolumnar junction zone. The percentage of HLA class II positive cells was low in CIN1 (40.9%), peaked in CIN2 (90.0%) and decreased again towards CIN3 lesions (71.4%) and cancer (63.6%). In CIN3 and cancers high CD3+ and CD8+ lymphocyte infiltration correlated with lack of or heterogeneous HLA class II antigen expression.
Our results suggest that HLA class II antigens are commonly expressed in precancerous stages and cervical cancers. The low percentage of HLA class II positive CIN1 lesions is compatible with the hypothesis that only a subset of CIN1, potentially those originating from the squamocolumnar junction zone, may overexpress HLA class II and tend to progress into high-grade CIN. In later disease stages, HLA class II antigen-positive cell clones may be eliminated in an environment of dense T cell infiltration, which would be compatible with the immunoediting concept.