Immunohistochemical studies have shown that loss of HLA expression is observed in cervical carcinomas but not in premalignant CIN lesions, indicating that downregulation of HLA is linked to tumor progression. The present study was performed to investigate whether the degree of HLA expression in cervical cancer correlates with more advanced disease as defined by histopathological features. Frozen tissue sections from 49 patients with squamous carcinoma of the cervix FIGO stage IB to IIB were stained with HLA class I monomorphic, locus- and allele-specific monoclonal antibodies. Histological data indicative of local disease, i.e., depth of invasion, tumor size, stage, and systemic spread of the disease, such as tumor-positive lymph nodes, were collected by reviewing the histological slides. Univariate analysis revealed that loss of HLA-A locus and A2-allele expression showed a positive, significant correlation with both presence of tumor-positive lymph nodes (P = 0.04 and 0.02, respectively) and the number of lymph nodes involved (both P = 0.04). These results strongly support the idea that, specifically in an immunogenic cancer type such as cervical cancer, tumor cells escape immunosurveillance and gain growth advantage by allele-specific downregulation of the HLA-A2 molecule. In view of the development of immunotherapeutical interventions in cancer, upregulation of HLA class I molecules may prove to be a useful additional tool in the combat against immunogenic tumors.