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.

Fatigue as a complicating factor in the recovery of breast cancer survivors treated at an oncology clinic in South West Nigeria: a case-control study.

Purpose: Recovering cancer survivors hope to return to their premorbid lifestyle after treatment and be free from the disease. They are, however, faced with some psychosocial issues, including fatigue, which could negatively impact their quality of life. With increasing cancer awareness and improvement in treatment, it is expected that the number of cancer survivors will increase in Nigeria. Little has, however, been done with regard to survivorship care in the country. It is important to explore fatigue in this group of patients with a view to find ways of reducing it to the barest minimum. Aim: To assess the level of fatigue in breast cancer survivors on follow-up visit at a radiation oncology clinic and compare it with age and sex-matched apparently healthy controls. Materials and Methods: Fatigue levels were obtained using the Fatigue Symptom Inventory (FSI). Kruskal-Wallis H test was used to compare the FSI scores in cases and controls. Chi-squared test was used for comparison of proportions. Level of significance was set at 5%. Results: Seventy cancer survivors (cases) and 70 apparently healthy age (±1)-matched controls were recruited. The prevalence of fatigue was higher among cases than controls (24.3% versus 10%; p = 0.025). Breast cancer survivors reported significantly worse fatigue on the day they were most fatigued (p = 0.017), least fatigued (0.047) and fatigued on average (p = 0.006) compared to controls. Fatigue also significantly interferes with the ability to concentrate (p = 0.040) and relate with people (p = 0.002) more in cases compared to controls. While fatigue was more common in the morning and afternoon in breast cancer survivors, fatigue either occurred more in the evening or followed no daily pattern in the controls. Conclusion: Breast cancer survivors reported worse fatigue, suggesting the need to include fatigue screening as part of post-treatment follow-up. There is also a need to investigate the factors responsible for this and explore ways of reducing or eliminating it.

Heterogeneity in head and neck cancer incidence among black populations from Africa, the Caribbean and the USA: Analysis of cancer registry data by the AC3.

BACKGROUND: Africa and the Caribbean are projected to have greater increases in Head and neck cancer (HNC) burden in comparison to North America and Europe. The knowledge needed to reinforce prevention in these populations is limited. We compared for the first time, incidence rates of HNC in black populations from African, the Caribbean and USA. METHODS: Annual age-standardized incidence rates (IR) and 95% confidence intervals (95%CI) per 100,000 were calculated for 2013-2015 using population-based cancer registry data for 14,911 HNC cases from the Caribbean (Barbados, Guadeloupe, Trinidad & Tobago, N = 443), Africa (Kenya, Nigeria, N = 772) and the United States (SEER, Florida, N = 13,696). We compared rates by sub-sites and sex among countries using data from registries with high quality and completeness. RESULTS: In 2013-2015, compared to other countries, HNC incidence was highest among SEER states (IR: 18.2, 95%CI = 17.6-18.8) among men, and highest in Kenya (IR: 7.5, 95%CI = 6.3-8.7) among women. Nasopharyngeal cancer IR was higher in Kenya for men (IR: 3.1, 95%CI = 2.5-3.7) and women (IR: 1.5, 95%CI = 1.0-1.9). Female oral cavity cancer was also notably higher in Kenya (IR = 3.9, 95%CI = 3.0-4.9). Blacks from SEER states had higher incidence of laryngeal cancer (IR: 5.5, 95%CI = 5.2-5.8) compared to other countries and even Florida blacks (IR: 4.4, 95%CI = 3.9-5.0). CONCLUSION: We found heterogeneity in IRs for HNC among these diverse black populations; notably, Kenya which had distinctively higher incidence of nasopharyngeal and female oral cavity cancer. Targeted etiological investigations are warranted considering the low consumption of tobacco and alcohol among Kenyan women. Overall, our findings suggest that behavioral and environmental factors are more important determinants of HNC than race.

Breast cancer pathology services in sub-Saharan Africa: a survey within population-based cancer registries.

BACKGROUND: Pathologists face major challenges in breast cancer diagnostics in sub-Saharan Africa (SSA). The major problems identified as impairing the quality of pathology reports are shortcomings of equipment, organization and insufficiently qualified personnel. In addition, in the context of breast cancer, immunohistochemistry (IHC) needs to be available for the evaluation of biomarkers. In the study presented, we aim to describe the current state of breast cancer pathology in order to highlight the unmet needs. METHODS: We obtained information on breast cancer pathology services within population-based cancer registries in SSA. A survey of 20 participating pathology centres was carried out. These centres represent large, rather well-equipped pathologies. The data obtained were related to the known population and breast cancer incidence of the registry areas. RESULTS: The responding pathologists served populations of between 30,000 and 1.8 million and the centres surveyed dealt with 10-386 breast cancer cases per year. Time to fixation and formalin fixation time varied from overnight to more than 72 h. Only five centres processed core needle biopsies as a daily routine. Technical problems were common, with 14 centres reporting temporary power outages and 18 centres claiming to own faulty equipment with no access to technical support. Only half of the centres carried out IHC in their own laboratory. For three centres, IHC was only accessible outside of the country and one centre could not obtain any IHC results. A tumour board was established in 13 centres. CONCLUSIONS: We conclude that breast cancer pathology services ensuring state-of-the-art therapy are only available in a small fraction of centres in SSA. To overcome these limitations, many of the centres require larger numbers of experienced pathologists and technical staff. Furthermore, equipment maintenance, standardization of processing guidelines and establishment of an IHC service are needed to comply with international standards of breast cancer pathology.

Cancers Attributable to Overweight and Obesity From 2012 to 2014 in Nigeria: A Population-Based Cancer Registry Study.

Background: Overweight and obesity are known risk factors for chronic diseases including cancers. In this study, we evaluated the age standardized incidence rates (ASR) and proportion of cancers attributable to overweight and obesity in Nigeria. Methods: We obtained incidence data from the databases of two population-based cancer registries (PBCRs) in Nigeria (Abuja and Enugu cancer registries), on cancer site for which there is established evidence of an association with overweight or obesity based on the International Agency for Research on Cancer (IARC) and the World Cancer Research Fund (WCRF) classification. We analyzed the data using population attributable fraction (PAF) for overweight or obesity associated cancers calculated using prevalence data and relative risk estimates in previous studies. Results: The two PBCRs reported 4,336 new cancer cases (ASR 113.9 per 100,000) from 2012 to 2014. Some 21% of these cancers were associated with overweight and obesity. The ASR for overweight and obesity associated cancers was 24.5 per 100,000; 40.7 per 100,000 in women and 8.2 per 100,000 in men. Overall, only 1.4% of incident cancers were attributable to overweight and obesity. The ASR of cancers attributable to overweight and obesity was 2.0 per 100,000. Postmenopausal breast cancer was the most common cancer attributable to overweight and obesity (n = 25; ASR 1.2 per 100,000). Conclusion: Our results suggest that a small proportion of incident cancer cases in Nigeria are potentially preventable by maintaining normal body weight. The burden of cancer attributed to overweight and obesity in Nigeria is relatively small, but it may increase in future.

Cancers Attributable to Alcohol Consumption in Nigeria: 2012-2014.

INTRODUCTION: Alcohol consumption has been identified as a risk factor for many cancers but less attention has been paid to the fraction of those cancers that are attributable to alcohol consumption. In this study, we evaluated the incidence and population attributable fraction (PAF) of cancers associated with alcohol consumption in Nigeria. METHODS: We obtained data on incidence of cancers from two population-based cancer registries (PBCRs) in Nigeria and identified cancer sites for which there is strong evidence of an association with alcohol consumption based on the International Agency for Research on Cancer Monograph 100E. We computed the PAF for each cancer site by age and sex, using prevalence and relative risk estimates from previous studies. RESULTS: Between 2012 and 2014 study period, the PBCRs reported 4,336 cancer cases of which 1,627 occurred in males, and 2,709 occurred in females. Of these, a total of 1,808 cancer cases, 339 in males and 1,469 in females, were associated with alcohol intake. The age standardized incidence rate (ASR) of alcohol associated cancers was 77.3 per 100,000. Only 4.3% (186/4,336) of all cancer cases or 10.3% (186/1,808) of alcohol associated cancers were attributable to alcohol consumption. Some 42.5% (79/186) of these cancers occurred in males while 57.5% (107/186) occurred in females. The ASR of cancers attributable to alcohol in this population was 7.2 per 100,000. The commonest cancers attributable to alcohol consumption were cancers of the oral cavity and pharynx in men and cancer of the breast in women. CONCLUSION: Our study shows that 4.3% of incident cancers in Nigeria can be prevented by avoiding alcohol consumption. While the incidence of cancers associated with alcohol intake is high, the proportion attributable to alcohol consumption is much lower suggesting that the number of cancers that may be prevented by eliminating alcohol intake in this population is relatively low.

Burden of Cancers Attributable to Infectious Agents in Nigeria: 2012-2014.

INTRODUCTION: Infections by certain viruses, bacteria, and parasites have been identified as risk factors for some cancers. In Nigeria, like many other developing countries, infections remain a leading cause of morbidity and mortality. While there are data on the incidence of different cancers in Nigeria, there has been no study of cancers attributable to infections. This study was carried out to determine the burden of cancers attributable to infections using data from two population-based cancer registries (PBCRs) in Nigeria. METHODS: We obtained data on cancers associated with EBV, human papillomavirus (HPV), hepatitis B and C, HIV, HHV8, Helicobacter pylori, and Schistosoma spp. from the databases of Abuja and Enugu cancer registries in Nigeria. We used population-attributable fraction for infections-associated cancers in developing countries that are based on prevalence data and relative risk estimates from previous studies. RESULTS: The PBCRs reported 4,336 incident cancer cases [age standardized incidence rate (ASR) 113.9 per 100,000] from 2012 to 2014, of which 1,627 (37.5%) were in males and 2,709 (62.5%) were in females. Some 1,030 (23.8%) of these cancers were associated with infections (ASR 44.4 per 100,000), while 951 (22.0%) were attributable to infections (ASR 41.6 per 100,000). Cancers of the cervix (n = 392, ASR 28.3 per 100,000) and liver (n = 145, ASR 3.4 per 100,000); and non-Hodgkin's lymphoma (n = 110, ASR 2.5 per 100,000) were the commonest infections-associated cancers overall. The commonest infectious agents associated with cancers in this population were HPV, EBV, hepatitis B and C, HIV, and HHV8. CONCLUSION: Our results suggest that 23.8% of incident cancer cases in this population were associated with infections, while 22.0% were attributable to infections. The infections attributable cancers are potentially preventable with strategies, such as vaccination, risk factor modification, or anti-infective treatment.

Developing National Cancer Registration in Developing Countries - Case Study of the Nigerian National System of Cancer Registries.

The epidemiological transition in sub-Saharan Africa (SSA) has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare. We report the implementation of a system for representative nation-wide cancer registration in Nigeria - the Nigerian National System of Cancer Registries (NSCR). The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low- and middle-income countries (LMIC) wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC.

Comparability, diagnostic validity and completeness of Nigerian cancer registries.

BACKGROUND: Like many countries in Africa, Nigeria is improving the quality and coverage of its cancer surveillance. This work is essential to address this growing category of chronic diseases, but is made difficult by economic, geographic and other challenges. PURPOSE: To evaluate the completeness, comparability and diagnostic validity of Nigeria's cancer registries. METHODS: Completeness was measured using children's age-specific incidence (ASI) and an established metric based on a modified Poisson distribution with regional comparisons. We used a registry questionnaire as well as percentages of death-certificate-only cases, morphologically verified cases, and case registration errors to examine comparability and diagnostic validity. RESULTS: Among the children's results, we found that over half of all cancers were non-Hodgkin lymphoma. There was also evidence of incompleteness. Considering the regional completeness comparisons, we found potential evidence of cancer-specific general incompleteness as well as what appears to be incompleteness due to inability to diagnose specific cancers. We found that registration was generally comparable, with some exceptions. Since autopsies are not common across Nigeria, coding for both them and death-certificate-only cases was also rare. With one exception, registries in our study had high rates of morphological verification of female breast, cervical and prostate cancers. CONCLUSIONS: Nigeria's registration procedures were generally comparable to each other and to international standards, and we found high rates of morphological verification, suggesting high diagnostic validity. There was, however, evidence of incompleteness.

Cancer burden among HIV-positive persons in Nigeria: preliminary findings from the Nigerian AIDS-cancer match study.

BACKGROUND: Although Nigeria has a large HIV epidemic, the impact of HIV on cancer in Nigerians is unknown. METHODS: We conducted a registry linkage study using a probabilistic matching algorithm among a cohort of HIV positive persons registered at health facilities where the Institute of Human Virology Nigeria (IHVN) provides HIV prevention and treatment services. Their data was linked to data from 2009 to 2012 in the Abuja Cancer Registry. Match compatible files with first name, last name, sex, date of birth and unique HIV cohort identification numbers were provided by each registry and used for the linkage analysis. We describe demographic characteristics of the HIV clients and compute Standardized Incidence Ratios (SIRs) to evaluate the association of various cancers with HIV infection. RESULTS: Between 2005 and 2012, 17,826 persons living with HIV (PLWA) were registered at IHVN. Their median age (Interquartile range (IQR)) was 33 (27-40) years; 41% (7246/17826) were men and 59% (10580/17826) were women. From 2009 to 2012, 2,029 clients with invasive cancers were registered at the Abuja Cancer Registry. The median age (IQR) of the cancer clients was 45 (35-68) years. Among PLWA, 39 cancer cases were identified, 69% (27/39) were incident cancers and 31% (12/39) were prevalent cancers. The SIR (95% CI) for the AIDS Defining Cancers were 5.7 (4.1, 7.2) and 2.0 (0.4, 3.5), for Kaposi Sarcoma and Cervical Cancer respectively. CONCLUSION: The risk of Kaposi Sarcoma but not Cervical Cancer or Non-Hodgkin's Lymphoma, was significantly increased among HIV positive persons, compared to the general population in Nigeria.

Cancer incidence in Nigeria: a report from population-based cancer registries.

INTRODUCTION: Cancer has become a major source of morbidity and mortality globally. Despite the threat that cancer poses to public health in sub-Saharan Africa (SSA), few countries in this region have data on cancer incidence. In this paper, we present estimates of cancer incidence in Nigeria based on data from 2 population-based cancer registries (PBCR) that are part of the Nigerian national cancer registry program. MATERIALS AND METHODS: We analyzed data from 2 population based cancer registries in Nigeria, the Ibadan Population Based Cancer Registry (IBCR) and the Abuja Population Based Cancer Registry (ABCR) covering a 2 year period 2009-2010. Data are reported by registry, gender and in age groups. We present data on the age specific incidence rates of all invasive cancers and report age standardized rates of the most common cancers stratified by gender in both registries. RESULTS: The age standardized incidence rate for all invasive cancers from the IBCR was 66.4 per 100000 men and 130.6 per 100000 women. In ABCR it was 58.3 per 100000 for men and 138.6 per 100000 for women. A total of 3393 cancer cases were reported by the IBCR. Of these cases, 34% (1155) were seen among males and 66% (2238) in females. In Abuja over the same period, 1128 invasive cancers were reported. 33.6% (389) of these cases were in males and 66.4% (768) in females. Mean age of diagnosis of all cancers in men for Ibadan and Abuja were 51.1 and 49.9 years respectively. For women, mean age of diagnosis of all cancers in Ibadan and Abuja were 49.1 and 45.4 respectively. Breast and cervical cancer were the commonest cancers among women and prostate cancer the most common among men. Breast cancer age standardized incidence rate (ASR) at the IBCR was 52.0 per 100000 in IBCR and 64.6 per 100000 in ABCR. Cervical cancer ASR at the IBCR was 36.0 per 100000 and 30.3 per 100000 at the ABCR. The observed differences in incidence rates of breast, cervical and prostate cancer between Ibadan and Abuja, were not statistically significant. CONCLUSION: Cancer incidence data from two population based cancer registries in Nigeria suggests substantial increase in incidence of breast cancer in recent times. This paper highlights the need for high quality regional cancer registries in Nigeria and other SSA countries.