Effect of anal epidermoid cancer-related viruses on the dendritic (Langerhans') cells of the human anal mucosa.

Abstract

The incidence of anal cancer is high in patients with anal condyloma. HIV increases this risk. We analyzed anal mucosa from normal individuals and individuals with condyloma. Normal anal mucosa from 155 consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with anal condyloma was compared with that obtained from 30 HIV-negative patients after hemorrhoid surgery (controls). Langerhans' cells (LCs), T lymphocytes, and viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus (HPV) types] in anal mucosa and HIV load and CD4 T-lymphocyte counts in the serum were characterized. None of the control individuals had anal squamous intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients with anal condyloma (P = 0.07). The number of LCs/mm in anal tissue was significantly higher in HIV-negative patients with condylomata (median, 30; range, 2-130) than in HIV-positive patients (median, 15; range, 0-100) or in controls (median, 17; range, 4-35). In HIV-negative individuals, the occurrence of condylomata was linked with a higher number of LCs. Significant differences were observed between HIV-positive and HIV-negative patients with anal condylomata:number of LCs/mm anal tissue, oncogenic HPV (26% versus 8%), other current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate regression analysis found HIV as the only risk factor for a decrease in the number of LCs (odds ratio, 6; 95% confidence interval, 2.28-16.1; P < 0.001) and the serum HIV load (odds ratio, 4.9; 95% confidence interval, 1.1-21.4 log/ml; P < 0.03) but not the serum CD4 T-lymphocyte rate as a predictive risk factor for having <17 LCs/mm tissue. HPV increases the number of LCs in anal mucosa in HIV-negative individuals. HIV alters anal dendritic cells, likely leading to an increase in anal cancer risk.