Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa.

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705.

Differences in patterns of high-risk human papillomavirus infection between urban and rural low-resource settings: cross-sectional findings from Mali.

BACKGROUND: The burden of cervical cancer is disproportionately high in low-resource settings. With limited implementation of human papillomavirus (HPV) vaccines on the horizon in the developing world, reliable data on the epidemiology of high-risk HPV (HR-HPV) infection in distinct geographic populations is essential to planners of vaccination programs. The purpose of this study was to determine whether urban patterns of HR-HPV occurrence can be generalized to rural areas of the same developing country, using data from Mali, West Africa, as an example. METHODS: Urban and rural women in Mali participated in a structured interview and clinician exam, with collection of cervical samples for HPV DNA testing, to determine HR-HPV prevalence and correlates of infection. Correlates were assessed using bivariate analysis and logistic regression. RESULTS: A total of 414 women (n=202 urban women; n=212 rural women) were recruited across both settings. The prevalence of HR-HPV infection in rural women was nearly twice that observed in urban women (23% v. 12%). Earlier age of sexual debut and fewer pregnancies were associated with HR-HPV infection among urban women, but not rural women. Twenty-six percent of urban women who had sexual intercourse by age 14 had an HR-HPV infection, compared to only 9% of those who had later sexual debut (p<0.01). Overall, age, income, and polygamy did not appear to have a relationship with HR-HPV infection. CONCLUSIONS: Compared to urban women, rural women were significantly more likely to be infected with high-risk HPV. The patterns and risk factors of HR-HPV infection may be different between geographic areas, even within the same developing country. The high prevalence in both groups suggests that nearly all rural women and most urban women in Mali will be infected with HR-HPV during their lifetime, so the effects of risk factors may not be statistically apparent. To control HPV and cervical cancer in West Africa and the rest of the developing world, planners should prioritize vaccination in high-burden areas.

Risk factors for high-risk human papillomavirus infection in unscreened Malian women.

OBJECTIVE: To investigate the epidemiology of human papillomavirus (HPV) infection in Malian women, for whom cervical cancer is the most common cancer and the second most common cause of cancer-related mortality. METHODS: Pilot study of 202 women aged 15-65 to determine the prevalence rate of high-risk HPV infection among unscreened Malian women. Information on risk factors was collected through a standardized, structured interview and clinical examination. High-risk (HR) HPV DNA was detected using signal amplification methods (hybrid capture II). RESULTS: High-risk HPV DNA was detected in 12% of unscreened women, while visual inspection after application of acetic acid and Lugol's iodine (VIA/VILI) identified suspicious abnormalities in 2.5% of unscreened women. Histopathological evaluation of VIA/VILI-positive biopsies revealed no evidence of cervical intraepithelial neoplasia or cervical cancer. The majority of infections occurred among women in the 15-24 year old range. Compared to women who were married or widowed, single women were 3.5 times more likely to be infected with HR HPV. CONCLUSIONS: The prevalence of infection with cancer causing types of HPV in this study was 12%. These prevalence estimates are consistent with what has been reported previously for other West African countries.