Detection of cytokines in cervicovaginal lavage in HIV-infected women and its association with high-risk human papillomavirus.

Background: Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population. Methods: IL-1ß, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA. Results: In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1ß (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines. Conclusion: We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.

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.