Memory Bvochora-Nsingo

Cervical cancer treatment outcomes and survival in Botswana by human immunodeficiency virus status: Ipabalele study results

Abstract Background Cervical cancer is a leading morbidity/mortality cause, frequently co-occurring with human immunodeficiency virus (HIV) positivity, in Botswana. We examined long-term outcomes for Ipabalele study participants receiving curative chemoradiation for locally advanced cervical cancer (2015-2019) by HIV status. Methods Clinical and outcome data were collected at baseline, treatment completion, and 3 months thereafter. Patients were followed for up to 5 years. Overall survival (OS) was evaluated using Kaplan-Meier curves and Cox regression. Results The cohort comprised 295 patients (73.8% with HIV, younger at diagnosis [P < .001]) followed for a median of 44.2 months. Complete response was seen in 217/278 (76.1%) patients. Two- and 5-year OS rates were 73.4% and 59.9%, respectively, with no difference by HIV status. OS was associated negatively with advanced disease stage (III: hazard ratio [HR] 13.23, P < .001; IV: HR 7.8, P = .008) and positively with increased radiation (HR 0.977, P = .0005) and chemotherapy (HR 0.85, P = .005). Clinical response was associated negatively with advanced disease (IV: HR 0.113, P = .002) and positively with increased radiation (P = .009). Toxicity did not differ by HIV status. The most common grade-≥-2 non-hematological and hematological toxicities were radiation dermatitis (39.8%) and reduced white blood cell count (66.05%), respectively. Conclusions In this cervical cancer cohort with good HIV status control, treatment outcomes and OS were associated with disease and treatment factors, not the HIV status. Early screening and education regarding treatment protocols are crucial to improve cervical cancer outcomes in Botswana.

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.