Evaluation of Langerhans' cells in the cervical epithelium of women with cervical intraepithelial neoplasia

Objective. Cervical infection with human papillomavirus (HPV) results in a more permissive environment for malignant transformation. In squamous epithelia the Langerhans' cell (LC) is responsible for antigen presentation. Studies that use S-100 immunostaining demonstrate low LCs in cervical intraepithelial neoplasia (CIN) while those that use other methods have shown normal numbers of LCs. This observation led us to postulate that a defect in S-100 proteins, not a simple decrease in LC number, may be the cause of immune suppression. To evaluate this we identified LCs in the cervix of women with HPV/CIN in a prospective fashion using two antibodies, S-100 and CD1, each targeting a different element of the LC. Methods. Paired biopsies of the cervix were taken, one paraffin embedded for S-100 and the other snap frozen for CD1. staining. LCs were counted and expressed as the number of cells per millimeter of epithelium. Analysis of variance was used to assess differences between counts in normal, low-grade, and high-grade lesions. HPV was tested by hybrid capture. Results. S-100 LCs were significantly reduced in dysplasia, LG 8.6 and HG 6.0, compared to normal at 16.7 cells/mm (P = 0.04). S-100 LCs were reduced in HPV-infected cases at 5.9 vs 12.8 cells/mm in NPV negatives (P = 0.02), Acute inflammatory infiltrates were associated with increased S-100 LCs independent of pathology. CD1 LCs were not significantly altered by any parameters tested. Conclusions. HPV/CIN may exert an immunosuppressive effect by decreasing the S-100 LCs, The association of S-100-positive LCs coupled with cervical inflammatory changes suggests an important function of the S-100 proteins ia the development of an anti-HPV-response. (C) 1999 Academic Press.