In situ FoxP3+ and IL-10 over-expression is associated with high grade anal lesions in HIV infected patients

Human papillomavirus (HPV) is the main etiologic agent of lower genital tract cancers. The natural history of HPV infection and the immune response to HIV/HPV co-infection, particularly in the anal mucosa, is poorly understood. The aim was evaluate the in situ immune response in anorectal biopsies from HIV-infected patients. A total of 114 biopsies were analyzed by Tissue Micro-Array: 15 were from HIV-negative individuals with normal squamous epithelium and 99 from HIV-positive individuals (21 normal squamous epithelium, 39 with anal intra-epithelial lesion grade 1 and 39 with anal intra-epithelial lesion grade 2/3). PCR and sequencing were used to identify HPV DNA. Staining for CD4, CD8, Foxp3+, T-bet and IL-10 were analyzed via immunohistochemistry. HIV-positive patients with AIN 2/3 showed a lower number of CD4+ cells (< 50 cells/mm3) compared to HIV negative subjects (P = 0.01). HIV infected individuals showed a higher expression of FoxP3+ and IL-10 that correlated with the severity of the lesion (P = 0.002). A positive coefficient correlation was found between FoxP3+ and IL-10 (r = 0.34; P = 0.027). HPV DNA was detected in 93.4% (101/107) of the samples and the most common types were HPV 16 (26.9%), followed by HPV 6 (15.7%), HPV 59 (13%) and HPV 18 (10.2%). Our results showed a strong association between the increased T-reg cells and IL-10 expression in HIV-positive patients with AIN 2/3. HPV 16 was the most prevalent type. Our study suggests that the immune regulatory in situ profile may favor HPV persistence in HIV-positive individuals. Further in situ studies should be done in order to elucidate the development of anal cancer in HPV/HIV co-infected individuals.