Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

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Abstract
Ninety-four cervical biopsies from normal tissue to high-grade squamous intraepithelial lesion (SILs) were examined for the presence of intraepithelial Langerhans' cells and subpopulations of stromal macrophages/dendrocytes by immunohistochemistry using anti-S100,-L1, -CD68 and -factor XIIIa antibodies. Human papillomavirus (HPV) detection was performed in all cases by using first a mixture of DNA probes for 14 HPV types commonly found in anogenital biopsies at low stringency conditions (Tm -40°C) and by reanalyzing the tissues at high stringency (Tm - 10°C) with HPV 6/11, 16/18 and 31/33/35 biotinylated probe cocktails and individual digoxigenin-labelled probes. SILs and metaplastic tissues were significantly associated with a depletion of S100-positive intraepithelial Langerhans' cells when compared with normal epithelium. In contrast, there was a significant increase in L1-positive stromal macrophages in SIL biopsies compared with normal or metaplastic cervix. A significantly higher density of CD68-positive macrophages was also observed in high-grade SILs compared with normal or metaplastic biopsies and with low-grade SILs. The density of factor XIIIa-positive dendrocytes was found to be higher in SILs compared with metaplastic tissues and in high-grade SILs when compared with normal cervical biopsies. No specific relationship was found between the densities of these cells and the HPV type detected in SILs separated into low grade and high grade. The significance of this inverse modulation of intraepithelial Langerhans' cells and stromal macrophages/dendrocytes in normal and SIL biopsies is discussed in relation to HPV infection and malignant transformation.