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Effect of Anal Epidermoid Cancer-related Viruses on the Dendritic (Langerhans’) Cells of the Human Anal Mucosa¹

Department of Gastroenterology and Oncology [I. S., F. W., T. A., L. A., D. H., J. C. S.]; INSERM Unité 410 [I. S., F. W., T. A., J. C. S.]; and Centre de Diagnostic Anonyme et Gratuit [A. C. C.], Hôpital Bichat-Claude Bernard 75877 Paris Cedex 18, France

Purpose: 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.

Experimental Design: 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.

Results: 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.

Conclusion: 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.