Human Immunodeficiency Virus Localization in Human Papillomavirus–Related, High‐Grade Squamous Intraepithelial Lesions of the Cervix in Women with HIV Infection: Microdissection and Molecular Analysis on Formalin‐Fixed and Paraffin‐Embedded Specimens

Objectives. To evaluate a possible mechanism of human immunodeficiency virus (HIV) and human papillomavirus (HPV) interaction, we have identified the cervical tissue compartments that harbor HIV. Materials and Methods. We studied 39 paraffin-embedded, cervical conization specimens with high-grade cervical intraepithelial neoplasia (CIN3) occurring in HIV-infected women. From selected intraepithelial HPV-positive nonulcerated specimens (confirmed by in situ hybridization), we obtained serial 4- to 5-μm-thick sections that were stained with hematoxylin and eosin, anti-S100 protein, and anti-CD4. The presence of intramucosal Langerhans' cells or dendritic cells or CD4-positive cells was recorded. Three consecutive, nonmicrodissected, full-thickness sections of the same specimens were used for polymerase chain reaction (PCR) analysis (group A). Three other uncovered, consecutive sections from the same blocks were examined with an inverted microscope, and full-thickness specimens of mucosa were dissected from the underlying cervical stroma, were gently removed, and were used for PCR (group B). The quality of DNA was checked by HLA-DQα amplification; then a nested PCR for HIV proviral DNA was performed. Results. Of group A, 5 of 39 cases (12.8%) were positive, whereas HIV was not detected in the microdissected sections of group B, with or without intraepithelial Langerhans' or CD4 cells. Conclusions. HIV does not affect cervical epithelium. The absence of infected Langerhans' or dendritic cells (or both) indicates a migration to the proximal lymph nodes of the infected cells. The absence of HIV proviral DNA in the CIN infiltrated by CD4 cells could be due to the low number or absence of infected CD4 cells.