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 epith elia the Langerhans' cell (LC) is responsible for antigen presentation. Stu dies that use S-100 immunostaining demonstrate low LCs in cervical intraepi thelial neoplasia (CIN) while those that use other methods have shown norma l numbers of LCs. This observation led us to postulate that a defect in S-1 00 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 wit h HPV/CIN in a prospective fashion using two antibodies, S-100 and CD1, eac h targeting a different element of the LC. Methods. Paired biopsies of the cervix were taken, one paraffin embedded fo r S-100 and the other snap frozen for CD1. staining. LCs were counted and e xpressed as the number of cells per millimeter of epithelium. Analysis of v ariance 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 ind ependent of pathology. CD1 LCs were not significantly altered by any parame ters tested. Conclusions. HPV/CIN may exert an immunosuppressive effect by decreasing th e S-100 LCs, The association of S-100-positive LCs coupled with cervical in flammatory changes suggests an important function of the S-100 proteins ia the development of an anti-HPV-response. (C) 1999 Academic Press.