Examining the Impact of HPV Infection and Clearance on HIV Susceptibility in the Female Genital Tract

Vaginal human papillomavirus (HPV) infection is associated with a 2-fold increased risk of HIV acquisition. We hypothesized that this might relate to HPV-associated genital immune alterations, either during chronic infection or immune clearance. 59 HIV-uninfected women were recruited from the African/Caribbean community in Toronto; 36 were HPV uninfected, and 23 were HPV infected. Cervical mononuclear cells collected by cytobrush were stained with T cell markers (CD3/ CD4/ CCR5/ CD69/ CD38/ HLA-DR/ CD25/ CD39), and dendritic cell markers (CD1a/ CD14/ CD11c/ DC-SIGN/ langerin /mannose receptor). HPV-positive participants returned after 6 months; 11 had cleared HPV, 8 were persistently infected with the same HPV type, 2 were lost to follow-up, and 2 partially cleared infection. There was no difference in cervical CD4 T cell subsets between HPV uninfected and infected women, or between women with persistent vs. cleared HPV infection, although there was an increase in Langerhans cells among women who cleared HPV compared to HPV uninfected women (P=0.015) and those with persistent HPV infection (P=0.023). Neither HPV infection nor clearance were associated with increased endocervical CD4+ HIV target cells, although Langerhans cell numbers were increased. Enhanced HIV susceptibility in HPV-infected women may be due to factors other than target cell recruitment.