Abstract
The development of cervical carcinoma is strongly associated with specific types of human papillomaviruses (HPVs). A role for cellular immunity in cervical disease is supported by the increased occurrence of HPV-associated lesions in immunosuppressed individuals. Upon viral infection or malignant transformation, ensuing alterations in gene expression result in the generation of novel sets of peptides which can form complexes with specific HLA class I heavy chains and beta 2-microglobulin. These are then expressed at the cell surface as potential targets for specific T cells. In this study of 100 carcinomas HLA-A and -B class I expression by the tumour cells was down-regulated at one or more alleles in at least 73% of cervical carcinomas. Interference with the transporter associated with antigen presentation (TAP), which translocates cytosolic peptides from endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of expression for common HLA class I alleles ranged from 36% to 71%, and such changes might be expected to influence specific immunogenic peptide presentation and consequent immune recognition. These results underline the importance of single as well as multiple allelic loss in cervical neoplasia and have important implications for attempts to intervene immunologically in cervical cancer.
Highlights
NHS Trust, Manchester M20 9BX, UK; 4North West Regional Tissue Typing Laboratories, St Mary's Hospital, Manchester M13
When W6/32 scored positive, individual alleles were scored as unknown (?) unless specific monoclonal antibodies (MAbs) could show that the tumour cells expressed the allele
The HLA-A25, -A32 crosssections of the Bw4 MAb were taken into account when interpreting the data
Summary
One hundred cervical cancers (94 squamous cell carcinomas, five adenosquamous/adenocarcinoma and one anaplastic tumour) were obtained consecutively from one operating list from women attending the Christie Hospital, Manchester, UK. Blood was collected preoperatively and biopsies were taken at the time of surgical staging before treatment with radiotherapy. Seven specimens of normal cervix were taken from women undergoing elective hysterectomy for benign conditions and in whom only previous normal cervical smears were documented. The distribution of stage determined at the time of radiotherapy was: stage I, 22; stage II, 40; stage III, 35; stage IV, 3. The incidence of HPV detection in these tumours was 74.1% HPV 16 (including three cases with HPV 16 and 18), 23.5% other HPV types (including 11, 1.2%; 18, 11.6%,; 31, 1.2%; 33, 2.3% and X, 7.0%) and 2.4% HPV negative, determined as previously described (Van de Brule et al, 1990)
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