Patients with Cervical Cancer with and without HIV Infection Have Unique T-cell Activation Profiles despite Similar Survival Outcomes after Chemoradiation

ABSTRACT: The global burden of cervical cancer is highest in low- and middle-income countries. Women living with human immunodeficiency virus (HIV) infection are particularly affected by cervical cancer despite availability and adherence to antiretroviral therapy. Immune profile correlates of survival and treatment response have not been widely explored in patients with and without HIV infection. This study recruited women with cervical cancer undergoing definitive chemoradiation (CRT) in Botswana. Clinical characteristics and blood samples were collected. Flow cytometry was performed on samples prior to initiation, at completion, and 3 months after CRT. Logistic regression analysis identified immune markers that differed by HIV status and correlated with overall survival (OS). The study enrolled 131 consecutive women (HIV+ N = 89 and HIV− N = 42). From initiation to 3 months after CRT, a significant decrease in CD4 frequency (72%–60.55%, P < 0.001) and an increase in CD8 frequency (20.9%–31.5%, P < 0.001) were seen in women without HIV, whereas no significant changes in CD4 frequency (52.5%–50.9%) or CD8 frequency (39.9%–41.4%) were observed in those with HIV. Peripheral T cells underwent similar activation across the cohort regardless of HIV status. Improved OS was associated with reduced frequency of IL-2–expressing CD4 T-cell subsets. In women living with HIV, enhanced OS was associated with the presence of proinflammatory CD8 T cells. CRT induces peripheral T-cell activation and distinct cytokine profiles that differ by HIV status. Despite similar OS, HIV infection may differentially affect immune response to CRT in women with well-managed HIV. SIGNIFICANCE: Chemoradiation affects the immune system of patients with cervical cancer with well-controlled HIV infection differently than those without HIV, yet their survival does not differ. This finding is an important step in understanding how management of HIV infection can modify cancer outcomes, particularly in settings with a high burden of HIV.