Genital Cytokines in HIV/Human Papillomavirus Co-Infection: A Systematic Review

Cervical cancer is the fourth cancer in incidence and the third in mortality among women worldwide. Women living with HIV have a significantly increased risk of cervical cancer. The immune response of the host is crucial to determine the course of the human papillomavirus (HPV) infection and cytokines play an important role modulating viral multiplication and concentrating the immune response in the Th1 or Th2 pattern. The aim of this study is to evaluate the available evidence on the concentration of genital cytokines and their role in HPV infection in HIV-infected women. A systematic search of the literature was performed using MEDLINE by PubMed, Embase, Cochrane, LILACS, Scopus, Science direct, and Web of Science databases on November, 2020, in which the following clusters of terms were applied: HIV infection, HPV infection, and cytokine. Initially, 728 articles were selected, but only 17 were eligible for full-text review, and among them, 9 were included in the qualitative analysis. No restriction was applied in language, publication date, or status. The most studied cytokines in the articles included in this review were interferon (IFN)-γ and interleukin (IL)-10 (six articles), tumor necrosis factor (TNF) and IL-6 (five articles), and macrophage inflammatory protein (four articles). The main findings show that there is a reduction in the number of cells expressing IFN-γ (p = .02) and TNF-α (p = .01), in the cervices of HIV-HPV co-infected women compared with those infected only by HPV. In addition, levels of IL-6 (p = .039) and IL-10 (p = .02) are increased in the cervical secretions of HIV-positive women compared to seronegative patients. Despite these findings, there is a clear need of larger studies to understand the role of these immune factors in HPV-induced cervical neoplasia of women co-infected with HIV.