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Uganda

Cancer Statistics
Population in 2008: 31.6m
People newly diagnosed with cancer (excluding NMSC) / yr: 27,100
Age-standardised rate, incidence per 100,000 people/yr: 171.9
Risk of getting cancer before age 75:17.8%
People dying from cancer /yr: 21,300
Data from IARC GlobalCan (2008)
Ugandan Cancer Organisations
Latest Research Publications related to Uganda

Ugandan Cancer Organisations (10 links)


Latest Research Publications related to Uganda

Chaabna K, Newton R, Vanhems P, et al.
Cancer incidence and all-cause mortality in HIV-positive patients in Northeastern Algeria before and during the era of highly active antiretroviral therapy.
J Cancer Res Ther. 2016 Apr-Jun; 12(2):576-81 [PubMed] Related Publications
AIMS: To assess cancer incidence and all-cause mortality trends in HIV-positive patients in Algeria before and during the highly active antiretroviral therapy (HAART) era.
SETTINGS AND DESIGN: Cross-sectional study.
SUBJECTS AND METHODS: We used hospital-based data of patients with HIV/AIDS between January 1988 and December 2010.
STATISTICAL ANALYSIS USED: Cancer incidence, standardized mortality ratios (SMRs), risk of death, and proportion of HIV-positive patients treated before and during the HAART era were calculated. The joinpoint model was used to assess the magnitude of changes in SMRs.
RESULTS: In 1988-2010, 156 patients were diagnosed as HIV-positive. During pre-HAART era, Kaposi sarcoma (KS) incidence was 5%. After the introduction of HAART, KS incidence decreased to 2%. No other AIDS-related cancer was diagnosed during the study. One-third died (52/156), of which 83.6% died in the same year as or in the year after HIV diagnosis; median age at death (interquartile range) was 34.5 (11.8) years. Yearly risk of death declined from 100% in 1998 to 8% in 2010; percentage of patients treated with HAART increased from 13% in 1998 to >80% after 2002. Overall SMR decreased from 200.2 (95% confidence interval [95% CI], 123.2-325.2) before the HAART era to 91.4 (95% CI, 66.0-126.6) thereafter. From 2003, yearly SMRs decreased significantly by 66.1% (P < 0.05) until 2006 but not thereafter.
CONCLUSIONS: Since 1998, the proportion of HIV-positive patients treated with HAART increased, reaching 84% in 2010, all-cause mortality decreased, and cancer remained rare. However, almost all patients who died during the study seemed to be diagnosed at a late stage of the disease, emphasizing the need for earlier diagnosis of HIV in Algeria.

Galukande M, Wabinga H, Mirembe F, et al.
Breast Cancer Risk Factors among Ugandan Women at a Tertiary Hospital: A Case-Control Study.
Oncology. 2016; 90(6):356-62 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Although East Africa, like other countries in sub-Saharan Africa, has a lower incidence of breast cancer than high-income countries, the disease rate is rising steeply in Africa; it has nearly tripled in the past few decades in Uganda. There is a paucity of studies that have examined the relation between reproductive factors and breast cancer risk factors in Ugandan women.
OBJECTIVE: To determine breast cancer risk factors among indigenous Ugandan women.
METHODS: This is a hospital-based unmatched case-control study. Interviews were conducted between 2011 and 2012 using structured questionnaires. Patients with histology-proven breast cancer were recruited over a 2-year period. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: A total of 350 women were recruited; 113 were cases and 237 were controls. The mean age was 47.5 years (SD 14) for the cases and 45.5 years (SD 14.1) for the controls. The odds of breast cancer risk seemed lower for those who breastfed (adjusted OR = 0.04; 95% CI: 0.01, 0.18). There was no significance for early age at first full-term birth (adjusted OR = 1.96; 95% CI: 0.97, 3.96; p = 0.061), and urban residence carried no increased odds of breast cancer either (p = 0.201).
CONCLUSION: Breastfeeding seems to be associated with reduced odds of breast cancer.

Gusev A, Shi H, Kichaev G, et al.
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
Nat Commun. 2016; 7:10979 [PubMed] Free Access to Full Article Related Publications
Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Hasahya OT, Berggren V, Sematimba D, et al.
Beliefs, perceptions and health-seeking behaviours in relation to cervical cancer: a qualitative study among women in Uganda following completion of an HPV vaccination campaign.
Glob Health Action. 2016; 9:29336 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cervical cancer remains a leading cause of morbidity and mortality in Uganda. Despite earlier information campaigns to introduce human papilloma virus (HPV) vaccination, which also targeted cervical cancer, misinterpretation and misunderstanding of the subject remain high. Women in Uganda present with cervical cancer at an advanced stage due to poor health-seeking behaviours, with an associated high mortality rate. This project explored beliefs, attitudes, perceptions, and health-seeking behaviours in relation to cervical cancer among women in Uganda after an HPV vaccination project had been rolled out.
DESIGN: A qualitative study design was used, with six focus group discussions (FGDs) that included 36 women, aged 25-49 years, with no previous history of cervical cancer symptoms or diagnosis. The women were interviewed in February and March 2013. The transcribed data was analysed using content analysis.
RESULTS: Three themes emerged: feeling unprotected and unsafe, misbelief and wondering about cervical cancer, and fear of the testing procedure. Participating women had heard of cervical cancer but preferred to wait to access cervical cancer screening until symptom debut.
CONCLUSIONS: There are still barriers to cervical cancer screening among women in Uganda, where there is a need for culture-specific, sensitive information and interventions to address the issues of improving the cervical cancer screening uptake among these women. Societal context needs to be taken into account when implementing community-based health education.

Ndejjo R, Mukama T, Musabyimana A, Musoke D
Uptake of Cervical Cancer Screening and Associated Factors among Women in Rural Uganda: A Cross Sectional Study.
PLoS One. 2016; 11(2):e0149696 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: In developing countries, inadequate access to effective screening for cervical cancer often contributes to the high morbidity and mortality caused by the disease. The largest burden of this falls mostly on underserved populations in rural areas, where health care access is characterized by transport challenges, ill equipped health facilities, and lack of information access. This study assessed uptake of cervical cancer screening and associated factors among women in rural Uganda.
METHODS: This descriptive cross sectional study was carried out in Bugiri and Mayuge districts in eastern Uganda and utilised quantitative data collection methods. Data were collected using a semi-structured questionnaire on cervical cancer screening among females aged between 25 and 49 years who had spent six or more months in the area. Data were entered in Epidata 3.02 and analysed in STATA 12.0 statistical software. Univariate, bivariate and multivariate analyses were performed.
RESULTS: Of the 900 women, only 43 (4.8%) had ever been screened for cervical cancer. Among respondents who were screened, 21 (48.8%) did so because they had been requested by a health worker, 17 (39.5%) had certain signs and symptoms they associated with cervical cancer while 16 (37.2%) did it voluntarily to know their status. Barriers to cervical cancer screening were negative individual perceptions 553 (64.5%) and health facility related challenges 142 (16.6%). Other respondents said they were not aware of the screening service 416 (48.5%). The independent predictors of cervical cancer screening were: being recommended by a health worker [AOR = 87.85, p<0.001], knowing where screening services were offered [AOR = 6.24, p = 0.004], and knowing someone who had ever been screened [AOR = 9.48, p = 0.001].
CONCLUSION: The prevalence of cervical cancer screening is very low in rural Uganda. Interventions to increase uptake of cervical cancer screening should be implemented so as to improve access to the service in rural areas.

Freeman E, Semeere A, Wenger M, et al.
Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.
BMC Cancer. 2016; 16:65 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data.
METHODS: We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure.
RESULTS: Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost.
CONCLUSIONS: In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.

Han Y, Rand KA, Hazelett DJ, et al.
Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.
J Natl Cancer Inst. 2016; 108(7) [PubMed] Article available free on PMC after 01/07/2017 Related Publications
The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

Semeere A, Wenger M, Busakhala N, et al.
A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.
Cancer Med. 2016; 5(5):914-28 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

Mwaka AD, Garimoi CO, Were EM, et al.
Social, demographic and healthcare factors associated with stage at diagnosis of cervical cancer: cross-sectional study in a tertiary hospital in Northern Uganda.
BMJ Open. 2016; 6(1):e007690 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
OBJECTIVE: To examine patient and primary healthcare factors and stage at diagnosis in women with cervical cancer in Northern Uganda with the intention to identify factors that are associated with advanced stages in order to inform policies to improve survival from cervical cancer in low income and middle income countries.
DESIGN: Cross-sectional hospital-based study.
SETTING: Tertiary, not-for-profit private hospital in postconflict region.
PARTICIPANTS: Consecutive tissue-diagnosed symptomatic patients with cervical attending care. Of 166 patients, 149 were enrolled and analysed.
PRIMARY OUTCOME: Cervical cancer stage at diagnosis.
RESULTS: Most women were diagnosed at stages III (45%) or IV (21%). After controlling for age, marital status, educational attainment and number of biological children, there was evidence for association between advanced stage at diagnosis and pre-referral diagnosis of cancer by primary healthcare professionals (adjusted OR (AOR)=13.04:95% CI 3.59 to 47.3), and financial difficulties precluding prompt help seeking (AOR=5.5:95% CI 1.58 to 20.64). After adjusting for age, marital status and educational attainment, women with 5-9 biological children (AOR=0.27:95% CI 0.08 to 0.96) were less likely to be diagnosed with advanced stage (defined as stages III/IV) cancer. In this pilot study, there was no statistical evidence for associations between stage at diagnosis, and factors such as age at diagnosis and marital status.
CONCLUSIONS: This study is a first attempt to understand the descriptive epidemiology of cervical cancer in rural Ugandan settings. Understanding individual patient factors, patients' behavioural characteristics and healthcare factors associated with advanced stage at diagnosis is essential for targeted effective public health interventions to promote prompt health seeking, diagnosis at early stage and improved survival from cervical cancer.

Tarricone R, Abu Koush D, Nyanzi-Wakholi B, Medina-Lara A
A systematic literature review of the economic implications of chemotherapy-induced diarrhea and its impact on quality of life.
Crit Rev Oncol Hematol. 2016; 99:37-48 [PubMed] Related Publications
INTRODUCTION: Chemotherapy-induced diarrhea (CID) diminishes physical performance, raises anxiety and depression levels, and increases healthcare resource utilization.
OBJECTIVE: To understand the impact that CID has on health-related quality of life (HRQoL) and on healthcare resource utilization.
METHODS: Systematic searches were conducted in MEDLINE, EMBASE, DARE, and the NHS EED databases.
RESULTS: A total of 22 articles were retrieved for full review (n=17, HRQoL; n=5 healthcare resource utilization). Only 2 studies had assessed HRQoL in patients experiencing CID, while cost studies demonstrated that CID episodes are unnecessarily expensive and can be avoided if diagnosed and treated early.
CONCLUSIONS: Better management of CID has the potential to reduce overall economic burden and improve patients' HRQoL. Available evidence also relays the need to conduct larger studies that assess HRQoL and consider cost beyond direct medical costs in order to understand the full impact of CID on HRQoL and healthcare resource utilization.

Tarricone R, Ricca G, Nyanzi-Wakholi B, Medina-Lara A
Impact of cancer anorexia-cachexia syndrome on health-related quality of life and resource utilisation: A systematic review.
Crit Rev Oncol Hematol. 2016; 99:49-62 [PubMed] Related Publications
INTRODUCTION: Cancer anorexia-cachexia syndrome (CACS) negatively impacts patients' quality of life (QoL) and increases the burden on healthcare resources.
OBJECTIVES: To review published CACS data regarding health-related QOL (HRQoL) and its economic impact on the healthcare system.
METHODS: Searches were conducted in MEDLINE, EMBASE, DARE, and NHS EED databases.
RESULTS: A total of 458 HRQoL and 189 healthcare resources utilisation abstracts were screened, and 42 and 2 full-text articles were included, respectively. The EORTC QLQ-C30 and FAACT instruments were most favoured for assessing HRQOL but none of the current tools cover all domains affected by CACS. Economic estimates for managing CACS are scarce, with studies lacking a breakdown of healthcare resource utilisation items.
CONCLUSIONS: HRQoL instruments that can better assess and incorporate all the domains affected by CACS are required. Rigorous assessment of costs and benefits of treatment are needed to understand the magnitude of the impact of CACS.

Nalwoga H, Ahmed L, Arnes JB, et al.
Strong Expression of Hypoxia-Inducible Factor-1α (HIF-1α) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer.
PLoS One. 2016; 11(1):e0146823 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
PURPOSE: Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1α and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1α expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1α in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer.
METHODS: Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1α and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons.
RESULTS: Strong HIF-1α expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1α expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression.
CONCLUSIONS: High HIF-1α expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1α and Axl as potential therapeutic targets in African breast cancer.

Amato T, Abate F, Piccaluga P, et al.
Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma.
Am J Clin Pathol. 2016; 145(1):116-27 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
OBJECTIVES: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma.
METHODS: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs).
RESULTS: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL.
CONCLUSIONS: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.

Huchko MJ, Maloba M, Nakalembe M, Cohen CR
The time has come to make cervical cancer prevention an essential part of comprehensive sexual and reproductive health services for HIV-positive women in low-income countries.
J Int AIDS Soc. 2015; 18(Suppl 5):20282 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
INTRODUCTION: HIV and cervical cancer are intersecting epidemics that disproportionately affect one of the most vulnerable populations in the world: women in low- and middle-income countries (LMICs). Historically, the disparity in cervical cancer risk for women in LMICs has been due to the lack of organized screening and prevention programmes. In recent years, this risk has been augmented by the severity of the HIV epidemic in LMICs. HIV-positive women are at increased risk for developing cervical precancer and cancer, and while the introduction of antiretroviral therapy has dramatically improved life expectancies among HIV-positive women it has not been shown to improve cancer-related outcomes. Therefore, an increasing number of HIV-positive women are living in LMICs with limited or no access to cervical cancer screening programmes. In this commentary, we describe the gaps in cervical cancer prevention, the state of evidence for integrating cervical cancer prevention into HIV programmes and future directions for programme implementation and research.
DISCUSSION: Despite the biologic, behavioural and demographic overlap between HIV and cervical cancer, cervical cancer prevention has for the most part been left out of sexual and reproductive health (SRH) services for HIV-positive women. Lower cost primary and secondary prevention strategies for cervical cancer are becoming more widely available in LMICs, with increasing evidence for their efficacy and cost-effectiveness. Going forward, cervical cancer prevention must be considered a part of the essential package of SRH services for HIV-positive women. Effective cervical cancer prevention programmes will require a coordinated response from international policymakers and funders, national governments and community leaders. Leveraging the improvements in healthcare infrastructure created by the response to the global HIV epidemic through integration of services may be an effective way to make an impact to prevent cervical cancer among HIV-positive women, but more work remains to determine optimal approaches.
CONCLUSIONS: Cervical cancer prevention is an essential part of comprehensive HIV care. In order to ensure maximal impact and cost-effectiveness, implementation strategies for screening programmes must be adapted and rigorously evaluated through a framework that includes equal participation with policymakers, programme planners and key stakeholders in the target communities.

Rand KA, Rohland N, Tandon A, et al.
Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.
Hum Mol Genet. 2016; 25(2):371-81 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

Mancuso N, Rohland N, Rand KA, et al.
The contribution of rare variation to prostate cancer heritability.
Nat Genet. 2016; 48(1):30-5 [PubMed] Related Publications
We report targeted sequencing of 63 known prostate cancer risk regions in a multi-ancestry study of 9,237 men and use the data to explore the contribution of low-frequency variation to disease risk. We show that SNPs with minor allele frequencies (MAFs) of 0.1-1% explain a substantial fraction of prostate cancer risk in men of African ancestry. We estimate that these SNPs account for 0.12 (standard error (s.e.) = 0.05) of variance in risk (∼42% of the variance contributed by SNPs with MAF of 0.1-50%). This contribution is much larger than the fraction of neutral variation due to SNPs in this class, implying that natural selection has driven down the frequency of many prostate cancer risk alleles; we estimate the coupling between selection and allelic effects at 0.48 (95% confidence interval [0.19, 0.78]) under the Eyre-Walker model. Our results indicate that rare variants make a disproportionate contribution to genetic risk for prostate cancer and suggest the possibility that rare variants may also have an outsize effect on other common traits.

Linet MS, Brown LM, Mbulaiteye SM, et al.
International long-term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0-19 years.
Int J Cancer. 2016; 138(8):1862-74 [PubMed] Related Publications
To enhance understanding of etiology, we examined international population-based cancer incidence data for lymphoid leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma and myeloid leukemia among children aged 0-19. Based on temporal trends during 1978-2007 in 24 populations, lymphoid leukemia and myeloid leukemia incidence rates generally have not changed greatly and differences in rates for non-Hodgkin and for Hodgkin lymphoma have diminished in some regions. Lymphoid leukemia rates during 2003-2007 in 54 populations varied about 10-fold, with rates highest in US white Hispanics (50.2 per million person-years) and Ecuador (48.3) and lowest in US blacks (20.4), Tunisia (17.7) and Uganda (6.9). Non-Hodgkin lymphoma rates varied 30-fold, with very high rates in sub-Saharan Africa (146.0 in Malawi and 54.3 in Uganda) and low rates (≤ 10) in some Asian populations (China, Japan, India, the Philippines and Thailand) and U.S. Asian-Pacific Islanders, eastern and northern European populations and Puerto Rico. Hodgkin lymphoma rates varied 15-fold, with rates highest in Italy (21.3) and lowest in China (1.7). Myeloid leukemia rates varied only about fivefold, with rates highest in the Philippines and Korea (exceeding 14.0) and lowest in Eastern Europe (5.9 in Serbia and 5.3 in the Czech Republic) and Uganda (2.7). The boy/girl average incidence rate ratios were 2.00 or lower. Age-specific patterns differed among the four hematopoietic malignancies, but were generally consistent within major categories world-wide, except for non-Hodgkin lymphoma. A systematic world-wide approach comparing postulated etiologic factors in low- versus high-risk populations may help clarify the etiology of these childhood malignancies.

Starita N, Annunziata C, Waddell KM, et al.
Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients.
Biomed Res Int. 2015; 2015:801353 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/10(5) cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n = 11) and B2 (n = 6). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions.

Abate F, Ambrosio MR, Mundo L, et al.
Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.
PLoS Pathog. 2015; 11(10):e1005158 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

Bukirwa A, Mutyoba JN, Mukasa BN, et al.
Motivations and barriers to cervical cancer screening among HIV infected women in HIV care: a qualitative study.
BMC Womens Health. 2015; 15:82 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: Cervical cancer is the second commonest cancer in women worldwide and the commonest cancer among women in Uganda. Annual cervical screening is recommended for women living with HIV for early detection of abnormal cervical changes, however uptake remains grossly limited. This study assessed factors associated with cervical screening uptake among HIV infected women at Mildmay Uganda where cervical screening using Visual inspection with acetic acid and iodine (VIA and VILI) was integrated into HIV care since July 2009.
METHODS: Eighteen (18) in-depth interviews with HIV infected women and 6 key informant interviews with health care providers were conducted in April 2013 to assess client, health care provider and facility-related factors that affect cervical screening uptake. In-depth interview respondents included six HIV infected women in each of the following categories; women who had never screened, those who had screened once and missed follow-up annual screening, and those who had fully adhered to the annual screening schedule. Data was analyzed using content analysis method.
RESULTS: Motivations for cervical cancer screening included the need for comprehensive assessment, diagnosis, and management of all ailments to ensure good health, fear of consequences of cervical cancer, suspicion of being at risk and the desire to maintain a good relationship with health care workers. The following factors negatively impacted on uptake of cervical screening: Myths and misconceptions such as the belief that a woman's ovaries and uterus could be removed during screening, fear of pain associated with cervical screening, fear of undressing and the need for women to preserve their privacy, low perceived cervical cancer risk, shortage of health workers to routinely provide cervical cancer education and screening, and competing priorities for both provider and patient time. Major barriers to repeat screening included limited knowledge and appreciation of the need for repeat screening, and lack of reminders.
CONCLUSIONS: These findings highlight the need for client-centered counseling and support to overcome fears and misconceptions, and to innovatively address the human resource barriers to uptake of cervical cancer screening among HIV infected women.

Amerson E, Woodruff CM, Forrestel A, et al.
Accuracy of Clinical Suspicion and Pathologic Diagnosis of Kaposi Sarcoma in East Africa.
J Acquir Immune Defic Syndr. 2016; 71(3):295-301 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in 2 East African countries.
METHODS: At 2 large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 on HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of US-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the US-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis.
RESULTS: Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% confidence interval: 74% to 79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59% and life-threatening diseases in 6%. Concordance between African pathologists and US-based dermatopathologists was 69% (95% confidence interval: 66% to 72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively.
CONCLUSIONS: Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region and augmentation of local dermatopathologic services.

Odongo J, Makumbi T, Kalungi S, Galukande M
Patient delay factors in women presenting with breast cancer in a low income country.
BMC Res Notes. 2015; 8:467 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: In low income countries, many patients with breast cancer present with advanced disease which is majorly attributed to late presentation and this is associated with poor survival rates. The aim of this study was to determine the magnitude of patient delay and the factors that influence, delay in seeking health care in female breast cancer patients.
METHODS: A cross-sectional study was done between January and April 2014 at a tertiary breast unit. Female patients with breast cancer above the age of 18 years were interviewed. Ethical approval was obtained.
RESULTS: In total 162 patients were recruited, the mean patient delay in months was 22.6 (SD = 26.4), median delay was 13 months and range was 1-127 months. 139 (89 %) patients delayed by more than 3 months after noticing symptoms of breast anomaly. Patients with no social support from spouses and family were more likely to delay (OR = 7.1, 95 % CI 2.4-21.5, p = 0.001), those who perceived the symptoms as very serious were less likely to delay (OR = 0.2, 95 % CI 0.1-0.6, p = 0.007). There was a significant association between delayed presentation and advanced stage at presentation (p = 0.006).
CONCLUSION: Most women (89 %) with breast cancer delayed by more than 3 months to seek the first medical consultation after noticing symptoms. Patients who had no social support from their families were more likely to delay.

Piccaluga PP, Navari M, De Falco G, et al.
Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas.
Oncotarget. 2016; 7(1):224-40 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown.In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative BL, to identify specific patterns relying on the differential expression and role of Epstein-Barr virus-encoded microRNAs.First, we found significant differences in the expression of viral microRNAs and in selected target genes. Among others, we identified LIN28B, CGNL1, GCET2, MRAS, PLCD4, SEL1L, SXX1, and the tyrosine kinases encoding STK10/STK33, all provided with potential pathogenetic significance. GCET2, also validated by immunohistochemistry, appeared to be a useful marker for distinguishing EBV-positive and EBV-negative cases. Further, we provided solid evidences that the EBV-encoded microRNAs (e.g. BART6) significantly mold the transcriptional landscape of Burkitt Lymphoma clones.In conclusion, our data indicated significant differences in the transcriptional profiles of EBV-positive and EBV-negative BL and highlight the role of virus encoded miRNA.

Erstad DJ, Tumusiime G, Cusack JC
Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications for the Clinical Surgeon.
Ann Surg Oncol. 2015; 22(11):3433-50 [PubMed] Related Publications
Colorectal cancer is a heterogeneous disease with a wide range of long-term outcomes and responses to treatment. Recent advances in the genetic and molecular characterization of tumors has yielded a set of prognostic and predictive biomarkers that aid the identification of patients at higher risk for disease recurrence and progression, and in some cases indicate the likelihood of response to a specific treatment. Increasingly, these biomarkers have become integral to the treatment algorithm for managing patients with colorectal cancer. Prognostic and predictive factors in colorectal cancer can broadly be categorized into treatment impact, clinicopathologic factors, and molecular markers. This review will focus primarily on molecular markers, which are foundational to the paradigmatic shift toward personalized cancer therapy.

Galukande M, Wabinga H, Mirembe F
Breast cancer survival experiences at a tertiary hospital in sub-Saharan Africa: a cohort study.
World J Surg Oncol. 2015; 13:220 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: Cancer of the breast is a major health burden and the most common cancer among women worldwide. Though its incidence is fourfold greater in high-income countries, in sharp contrast, mortality rates are greatest among the low-income countries. Early detection linked to appropriate treatment is the most effective strategy to improve survival. The purpose of this study therefore was to establish the survival experiences of women with breast cancer at a Ugandan hospital.
METHODS: This study is an observational analytical study. It involved 262 women during the periods 2004 to 2007 and 2010 to 2012. Kaplan Meier method and Cox regression were used to calculate breast cancer mortality and cumulative survival experiences.
RESULTS: Sixty-three out of 262 (23%) deaths were observed; mean age was 45 years, and 91 observations ended on or before follow-up. Luminal B median survival was months. The 5-year cumulative survival was 51.8 %. There were no stage I and II deaths. There were no differences in survival by phenotype adjusted for age, but there were differences for stage IV (p=0.05).
CONCLUSIONS: The cumulative 5-year survival was 51.8 %. The burden of advanced disease and associated mortality were high, and a significant number of patients were lost to follow-up after their first contact.

Byakwaga H, Hunt PW, Laker-Oketta M, et al.
The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa.
J Acquir Immune Defic Syndr. 2015; 70(3):296-303 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: Other than Kaposi sarcoma (KS)-associated herpesvirus and CD4 T-cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T-cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.
METHODS: In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography-tandem mass spectrometry.
RESULTS: We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, interquartile range: 90 to 190 nM/μM) than KS cases (110, interquartile range: 90 to 150 nM/μM) (P = 0.004). After adjustment for age, sex, CD4 count, and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% confidence interval: 27% to 77%) in the odds of KS compared with those with the lowest (first quartile) levels. KS was also independently associated with lower CD4 count, higher plasma HIV RNA, and men.
CONCLUSIONS: Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.

Moses E, Pedersen HN, Mitchell SM, et al.
Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.
Trop Med Int Health. 2015; 20(10):1355-67 [PubMed] Related Publications
OBJECTIVES: To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA).
METHODS: Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates.
RESULTS: In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing.
CONCLUSIONS: This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA.

Twinomujuni C, Nuwaha F, Babirye JN
Understanding the Low Level of Cervical Cancer Screening in Masaka Uganda Using the ASE Model: A Community-Based Survey.
PLoS One. 2015; 10(6):e0128498 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Cervical cancer is one of the leading causes of cancer deaths among women globally and its impact is mostly felt in developing countries like Uganda where its prevalence is higher and utilization of cancer screening services is low. This study aimed to identify factors associated with intention to screen for cervical cancer among women of reproductive age in Masaka Uganda using the attitude, social influence and self efficacy (ASE) model. A descriptive community based survey was conducted among 416 women. A semi-structured interviewer administered questionnaire was used to collect data. Unadjusted and adjusted prevalence ratios (PR) were computed using a generalized linear model with Poisson family and a log link using STATA 12. Only 7% (29/416) of our study respondents had ever screened for cervical cancer although a higher proportion (63%, 262/416) reported intention to screen for cervical cancer. The intention to screen for cervical cancer was higher among those who said they were at risk of developing cervical cancer (Adjusted prevalence ratio [PR] 2.0, 95% CI 1.60-2.58), those who said they would refer other women for screening (Adjusted PR 1.4, 95% CI 1.06-1.88) and higher among those who were unafraid of being diagnosed with cervical cancer (Adjusted PR 1.6, 95% CI 1.36-1.93). Those who reported discussions on cervical cancer with health care providers (Adjusted PR 1.2, 95% CI 1.05-1.44), those living with a sexual partner (Adjusted PR 1.4, 95% CI 1.11-1.68), and those who were formally employed (Adjusted PR 1.2, 95% CI 1.03-1.35) more frequently reported intention to screen for cervical cancer. In conclusion, health education to increase risk perception, improve women's attitudes towards screening for cervical cancer and address the fears held by the women would increase intention to screen for cervical cancer. Interventions should also target increased discussions with health workers.

Ahmed L, Nalwoga H, Arnes JB, et al.
Increased tumor cell expression of Axl is a marker of aggressive features in breast cancer among African women.
APMIS. 2015; 123(8):688-96 [PubMed] Related Publications
Axl, a receptor tyrosine kinase belonging to the Tyro/Axl/Mer (TAM) family, has been shown to be overexpressed in breast cancer with poor outcome. Moreover, Axl was associated with a basal-like phenotype (BLP) in these tumors. Our aim was to investigate Axl expression in breast cancers from an African population since these tumors are known to be aggressive and have a high frequency of the basal-like phenotype. We studied 170 paraffin-embedded breast carcinoma cases by tissue microarrays and immunohistochemical methods. In total, 128 tumor cases (75%) had strong Axl expression and 42 cases (25%) had weak or negative staining. Strong expression of Axl was associated with high tumor grade (p < 0.0005), estrogen receptor (ER) negativity (p = 0.024), p53 expression (p = 0.004), P-cadherin positivity (p = 0.017), and basal-like phenotypic profiles BLP2 (p = 0.033) and BLP3 (p = 0.022). In addition, Axl overexpression also showed an association with markers of tumor cell proliferation and tumor angiogenesis. In conclusion, our findings indicate strong expression of Axl in a high proportion of breast cancer cases among African women and associations with markers of aggressive features, indicating poor prognosis. These findings suggest Axl as a potential therapeutic target in this population.

Campos NG, Castle PE, Wright TC, Kim JJ
Cervical cancer screening in low-resource settings: A cost-effectiveness framework for valuing tradeoffs between test performance and program coverage.
Int J Cancer. 2015; 137(9):2208-19 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between (i) test sensitivity and screening coverage; (ii) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and (iii) test sensitivity, screening coverage and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates and programmatic costs are needed to guide decision making for cervical cancer screening.

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