Colorectal adenocarcinoma in Uganda: are right-sided and left-sided colon cancers two distinct disease entities?

INTRODUCTION: In Western countries, right-sided colon cancers (RSCC) present at an older age and advanced stage. Researchers believe that there is a difference between left-sided colon cancer (LSCC) and RSCC. In Uganda, however, it is unknown whether differences exist in the pathological profile between RSCC and LSCC. The aim of this study was to determine the differences in clinicopathological characteristics between RSCC and LSCC in Ugandan patients. METHODOLOGY: A cross-sectional study was conducted in which colorectal adenocarcinoma formalin-fixed paraffin-embedded tissue (FFPE) blocks were obtained from 2008 to 2021. Colorectal specimens were obtained from prospectively recruited patients. In the retrospective study arm, FFPE blocks and data were obtained from the archives of pathology laboratory repositories. Parameters studied included age, sex, location of the tumour, grade, stage, lymphovascular (LVI) status, and histopathological subtype between LSCC and RSCC. RESULTS: Patients with RSCC were not older than those with LSCC (mean age, 56.3 years vs 53.5 years; p = 0.170). There was no difference in the stage between RSCC and LSCC. Poorly differentiated tumours were more commonly found in RSCC than in LSCC (18.7% vs 10.1%; p = 0.038). Moderately and poorly differentiated colonic tumours were more common with RSCC (89.3%) than with LSCC (75.1%) (p = 0.007). Younger patients had more poorly differentiated tumours than older patients (19.6% versus 8.6%; p = 0.002). LVI was more common with RSCC than with LSCC (96.8% vs 85.3%; p = 0.014). Mucinous adenocarcinoma (MAC) was more common with RSCC (15.8%) compared with LSCC (8.5%) (p = 0.056) although statistical significance was borderline. CONCLUSIONS: Clinicopathological features of RSCCs tend to be different from those of LSCCs. RSCCs tend to be associated with MAC, a higher grade and LVI status compared to LSCC. LSCC and RSCC present predominantly with an advanced stage; therefore, national screening programmes for the early detection of CRC are necessary to reduce mortality in our Ugandan population.

Dietary risk factors for colorectal cancer in Uganda: a case-control study.

INTRODUCTION: Low-income countries in East Africa have a lower incidence of colorectal cancer (CRC) than high-income countries; however, the incidence has steadily increased in the last few decades. In Uganda, the extent to which genetic and environmental factors, particularly dietary factors, contribute to the aetiology of CRC is unclear. Therefore, the objective of our study was to determine the relationship between dietary factors and CRC in Uganda. METHODS: We conducted a case-control study and recruited 128 cases and 256 controls, matched for age (± 5 years) and sex. Data regarding the frequency of consumption of the dietary factors were obtained from all the participants using an interview-based questionnaire. The potential dietary risk factors and protective factors evaluated included the type and frequency of meat consumed and the type and frequency of high-fibre foods consumed. The frequency was either 4 or more times/week, 2-3 times/week, once/week or never. Conditional logistic regression analyses were used to determine the odds ratios associated with the different risk and protective factors. RESULTS: The median age (IQR) for the case participants was 55.5 (43-67.5) years, and that of the control participants was 54 (42-65) years. The male-to-female ratio was 1:1 for all the participants. Factors significantly associated with CRC cases included:- the consumption of boiled beef 2-3 times/week (aOR:3.24; 95% CI: 1.08-9.69; p < 0.035). Consumption of high-fibre foods, including:- millet for ≥ 4 times/week (aOR: 0.23; 95% CI: 0.09-0.62; p = 0.003)), spinach for ≥ 4 times/week (aOR:0.32; 95% CI: 0.11-0.97; p = 0.043), and potatoes 2-3 times/week (aOR: 0.30; 95% CI: 0.09-0.97; p = 0.044), were protective against CRC. Boiled cassava showed a tendency to reduce the likelihood of CRC when consumed ≥ 4 times/week (aOR:0.38; 95% CI: 0.12-1.18) however this did not reach statistical significance (p = 0.093). CONCLUSIONS: The consumption of boiled beef increases the risk of CRC, while the intake of high-fibre foods may reduce the risk of CRC among Ugandans. We recommend nutritional educational programmes to increase public awareness regarding the protective role of a high-fibre diet and to limit the intake of cooked meat in our Ugandan population.

Human papillomavirus distribution in invasive cervical carcinoma in sub-Saharan Africa: could HIV explain the differences?

OBJECTIVES: To describe human papillomavirus (HPV) distribution in invasive cervical carcinoma (ICC) from Mali and Senegal and to compare type-specific relative contribution among sub-Saharan African (SSA) countries. METHODS: A multicentric study was conducted to collect paraffin-embedded blocks of ICC. Polymerase chain reaction, DNA enzyme immunoassay and line probe assay were performed for HPV detection and genotyping. Data from SSA (Mozambique, Nigeria and Uganda) and 35 other countries were compared. RESULTS: One hundred and sixty-four ICC cases from Mali and Senegal were tested from which 138 were positive (adjusted prevalence = 86.8%; 95% CI = 79.7-91.7%). HPV16 and HPV18 accounted for 57.2% of infections and HPV45 for 16.7%. In SSA countries, HPV16 was less frequent than in the rest of the world (49.4%vs. 62.6%; P < 0.0001) but HPV18 and HPV45 were two times more frequent (19.3%vs. 9.4%; P < 0.0001 and 10.3%vs. 5.6%; P < 0.0001, respectively). There was an ecological correlation between HIV prevalence and the increase of HPV18 and the decrease of HPV45 in ICC in SSA (P = 0.037 for both). CONCLUSION: HPV16/18/45 accounted for two-thirds of the HPV types found in invasive cervical cancer in Mali and Senegal. Our results suggest that HIV may play a role in the underlying HPV18 and HPV45 contribution to cervical cancer, but further studies are needed to confirm this correlation.

Prognostic Factors for Survival of Colorectal Adenocarcinoma Patients in Uganda.

BACKGROUND: In Uganda, similar to other countries in East Africa, the incidence of colorectal cancer (CRC) has been steadily increasing. This increase in incidence is accompanied by a poor prognosis. There is limited knowledge on factors responsible for the poor outcome of patients with CRC in Uganda. Cancer survival analysis is one way of determining some of these prognostic factors. The aim of this study was to determine prognostic factors associated with CRC survival in Ugandan patients. METHODS: This was a retroprospective cohort study involving patients with linked data in the Kampala cancer registry and medical records from hospitals in Uganda. Participants with a diagnosis of colorectal adenocarcinoma between 1st January 2008 and 31st December 2018 were included. Variables included patients' demographic data, grade, stage and location of CRC, data on whether a patient was operated on, type of operation, treatment modalities and date of diagnosis. Our outcome variable was time to death after diagnosis. We computed and compared survival using the Log rank test and used Cox proportional hazards regression to determine factors associated with survival. RESULTS: A total of 247 patients were included in the study with a mean (SD) age of 53.3 (15.7) years and a female: male ratio of 1.14:1. The proportions of patients surviving at 1, 2 and 3 years were 65.2% (95% CI: 58.8-70.9), 42.0% (95% CI:35.6-48.3) and 33.3% (95% CI:27.3-39.4) respectively. In multivariate analysis, factors associated with increased mortality included clinical stage II (aHR = 2.44, 95% CI: 1.10-5.41, p=0.028), stage III (aHR=2.65, 95% CI: 1.31-5.39, p=0.007) and stage IV (aHR=5.47, 95% CI: 2.40-12.48, p<0.001). Curative surgery alone (aHR=0.63, 95% CI: 0.39-1.01, p=0.057) and curative surgery with chemotherapy (aHR=0.53, 95% CI: 0.32-0.88, p=0.015) were associated with a better survival. CONCLUSION: The survival rate among CRC patients in Uganda is low. Advanced stage CRC accelerates mortality, while surgery alone or in combination with chemotherapy improves survival. Implementation of national screening programmes for early diagnosis of CRC and increasing surgery and oncology infrastructure is recommended to improve the CRC survival rate in the Ugandan population.

Risk Factors for Colorectal Adenocarcinoma in an Indigenous Population in East Africa.

Introduction: The incidence of colorectal cancer (CRC) is increasing in East Africa. Changes in lifestyle and dietary changes, particularly alcohol consumption, smoking, and consumption of cooked meats with a reduction in fibre in the diet may be responsible. The objective of our study was to determine the risk factors responsible for CRC in Uganda. Methods: We recruited 129 participants with histologically proven colorectal adenocarcinoma and 258 control participants from four specialized hospitals in central Uganda from 2019 to 2021. Controls were block matched for age (±5 years) and sex of the case participants. The risk factor variables included; area of residence, tribe, body mass index (BMI), smoking, alcohol consumption and family history of gastrointestinal cancer. We used conditional or ordinal logistic regression to obtain crude and adjusted odds ratios for risk factors associated with CRC. Results: In bivariate analysis, case participants were more likely to be associated with urban residence (cOR:62.11; p<0.001); family history of GI cancer (cOR: 14.34; p=0.001); past smokers (cOR: 2.10; p=0.080); past alcohol drinkers (cOR: 2.35; p=0.012); current alcohol drinkers (cOR: 3.55; p<0.001); high BMI 25-29.9 kg/m2 (cOR: 2.49; p<0.001); and high BMI ≥30kg/m2 (cOR: 2.37; p=0.012). In the multivariate analysis, urban residence (aOR: 82.79; p<0.001), family history of GI cancer (aOR: 61.09; p<0.001) and past smoking (aOR: 4.73; p=0.036) were independently associated with a higher risk of developing CRC. Conclusion: A family history of gastrointestinal cancer was a risk factor for CRC. While population-based CRC screening may not be feasible in low income-countries, targeted CRC screening for first-degree relatives with CRC should be considered in East Africa. Molecular genetic studies need to be carried out to determine the role of hereditary factors in our population. Prevention strategies should be adopted to avoid smoking in our population which was associated with an increased risk of CRC.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Primary Osteosarcoma of the Breast with Extensive Chondroid Matrix in a Teenager Female Patient: The Paradoxical Diagnosis in Breast Mastopathy.

PURPOSE: Non-epithelial tumors of the breast are extremely rare and have an incidence of less than 1%. The most common non-epithelial breast tumor is the phyllodes tumor (PT), which accounts for 61%. Primary osteosarcomas of the breast contribute up to only 12.5% of all breast sarcomas. In young females, osteosarcomas are extremely rare, especially in those without a previous history of primary bone osteosarcoma. A case of a 16-year old female with primary osteosarcoma of the breast (POB) with extensive chondroid matrix involving the left breast is herein presented. CASE REPORT: This report describes a 16-year old female with neither a previous history of bone osteosarcoma nor family history of breast cancer who was diagnosed with a primary chondroblastic osteosarcoma of the left breast. The mass was shining, warm, firm, and slightly fixed. The excisional biopsy showed a large tumor measuring 11x9x7 cm which was encapsulated, grayish-white, and nodular. CONCLUSION: Primary osteosarcomas of the breast carry a poor prognosis by being triple negative and because of being the rarest tumors, they pose a challenge in managing the patients due to lack of established treatment modalities.

Prognostic Factors for Overall Survival of Patients with Prostate Cancer in Kyadondo County, Uganda.

BACKGROUND: Prostate cancer is the second most common cancer among men globally. A few studies that have been done in Uganda on survival of patients with prostate cancer indicate that, the overall survival of patients with prostate cancer in Uganda is poor. The aim of this study was to determine the 3-year overall survival rate of a cohort of patients with prostate cancer residing in Kyadondo County who were diagnosed from 2012 to 2014. The secondary objective was to correlate the overall survival with the clinicopathological prognostic factors. MATERIALS AND METHODS: This was a retrospective cohort study which involved 136 patients who were diagnosed histologically with prostate cancer at the department of pathology between 2012 and 2014. The cases were registered at the Kampala cancer registry and followed up to 31st December 2017. Data analysis was done using STATA version 12.0. The Kaplan-Meir curves were used for analysis of the 3-year overall survival rate. Hazard ratio (HR) and Log-rank test at 95% confidence interval under Cox-regression model were used to evaluate the effect of the covariates on the 3-year overall survival rate. p < 0.05 was considered statistically significant. RESULTS: More than half of the cases, 55.9% (n = 76) had Gleason score >8. Most of the patients, 67.7% (n = 92) had advanced disease at diagnosis. The 3-year overall survival rate was 67.6% with median survival of 36.5 months and range of 0-65 months. Clinical stage of the patients (HR = 1.65, p = 0.039), Gleason score (HR = 1.88, p = 0.008), and lymphovascular invasion (HR = 0.37, p = 0.002) were the independent predictors of the 3-year overall survival rate in this study. Conclusion. The 3-year overall survival of prostate cancer patients in Uganda is poor. Most of the patients with are diagnosed with advanced clinical stages (stage III and IV). The Gleason score, clinical stage and lymphovascular invasion can powerfully predict independently the overall survival of patients with prostate cancer. This implies that the Gleason score, clinical stage and lymphovascular invasion may be used to predict the overall survival of patients with prostate cancer even prior prostatectomy.

Human Papillomavirus type distribution in invasive cervical cancer in Uganda.

BACKGROUND: We conducted a study aiming to describe Human Papillomavirus (HPV) type distribution in invasive cervical carcinoma in Uganda. METHODS: 191 archival cervical carcinoma samples diagnosed in the Department of Pathology, Makerere University in Kampala between 1968 and 1992 were analysed using a sensitive PCR-Reverse Hybridization Line Probe Assay. RESULTS: Out of the 186 cases of confirmed invasive cervical cancer in the study paraffin blocks, 114 were positive for HPV DNA. Specific HPV genotypes were identifiable in 109 cases: HPV 16, 18, 31, 35, 39, 44, 45, 51, 52 and 70. These occurred as single infections in 105 cases (96.3%) and as multiple infections in 4 cases (3.7%). HPV 16 or 18 accounted for 80% (84/105) of cases with single infection. CONCLUSION: The results of this study confirm the role of HPV 16 and 18 in cervical cancer pathogenesis in the Ugandan population. The results suggest that the currently available HPV vaccines against HPV 16 and 18 could possibly prevent the majority of invasive cervical cancers in Uganda.

Burden of Placental Malaria among Pregnant Women Who Use or Do Not Use Intermittent Preventive Treatment at Mulago Hospital, Kampala.

Intermittent preventive treatment of malaria in pregnancy with sulphadoxine-pyrimethamine (SP-IPTp) is widely used to reduce the incidence of adverse pregnancy outcomes. As a monitor for continued effectiveness of this intervention amidst SP resistance, we aimed to assess malaria burden among pregnant women who use or do not use SP-IPTp. In a descriptive cohort study at Mulago Hospital, Kampala, 87 women who received two supervised doses of SP-IPTp were followed up until delivery. Controls were pregnant women presenting in early labour without history of SP-IPTp. Histopathological investigation for placental malaria (PM) was performed using the Bulmer classification criterion. Thirty-eight of the 87 women returned for delivery and 33 placentas were successfully collected and processed along with 33 placentas from SP nonusers. Overall, 12% (4/33) of the users had evidence of PM compared to 48% (16/33) of nonusers. Among nonusers, 17/33, 8/33, 2/33, and 6/33 had no placental infection, active infection, active-chronic infection, and past-chronic infection, respectively. Among users, respective proportions were 29/33, 2/33, 0/33, and 2/33. No difference in birth weights was apparent between the two groups, probably due to a higher proportion of infections occurring later in pregnancy. Histological evidence here suggests that SP continues to offer substantial benefit as IPTp.

Reduced plasma concentrations of vitamin B6 and increased plasma concentrations of the neurotoxin 3-hydroxykynurenine are associated with nodding syndrome: a case control study in Gulu and Amuru districts, Northern Uganda.

INTRODUCTION: Nodding syndrome was first reported in Uganda in 2003 among internally displaced populations. Risk factors for the syndrome remain unknown. We therefore explored vitamin B6 deficiency and resulting high 3-hydroxykynurenine (3-HK) levels as risk factor for nodding syndrome in Northern Uganda. METHODS: Case-control study conducted in Gulu and Amuru districts. Cases were children/young adults with nodding syndrome. Healthy children/young adults were recruited as controls from same community as cases. Data on socio-demographic and other risk factors was collected using questionnaires. Whole blood was collected in EDTA tubes for assay of 3-HK and vitamin B6 using sandwich ELISA. Conditional logistic regression model was used to assess associations. RESULTS: 66 cases and 73 controls were studied. Factors associated with nodding syndrome were being positive for 3-HK (AOR=4.50, p=0.013), vitamin B6 concentration below mean (AOR=7.22, P=0.001), child being taken care of by mother only (AOR=5.43, p=0.011), child being taken care of by guardian (AOR=5.90, p=0.019) and child consuming relief food at weaning (AOR=4.05, p=0.021). CONCLUSION: Having low vitamin B6 concentration which leads to a build up of 3-hydroxykynurenine concentration in cases as a main risk factor. Therefore, cases should be treated with vitamin B6 and community members should be sensitise to ensure adequate dietary intake of vitamin B6 so that the risk of nodding syndrome among children is averted. We encourage future prospective intervention study to be conducted to assess the effect of low vitamin B6 on the development of nodding syndrome via raised 3-HK concentration.

High Prevalence of Malnutrition among the Above Thirteen with Primary Pyomyositis in Northern Uganda.

AIM: To determine the prevalence of malnutrition and its association with primary pyomyositis among patients and controls who were age and sex matched. STUDY DESIGN AND SETTING: A case-control study was conducted at Gulu Regional, Lacor, Kalongo, Kitgum and St. Joseph's Hospitals in Northern Uganda. STUDY DURATION: Study was conducted from September 2011 to November 2013. METHODS: Primary pyomyositis patients were consecutively recruited to these Hospitals and were age and sex-matched with controls selected during the same period. History, physical examinations, Body Mass Index (BMI), blood samples for haematology, biochemistry, clinical chemistry and muscle biopsy for histology were obtained. Those that did not meet the inclusion criteria were excluded. The study was approved by the Ethics and Review Committee of Gulu University Medical School. RESULTS: During the study period, 63 patients and 63 controls were recruited; 29 females and 34 males. Among primary pyomyositis patients, 59 (93.7%) had malnutrition while there were 2 in the control group, giving a prevalence of 3.2%.The matched analysis produced an aOR of 449.875 with a 95% CI (79.382, 2549.540; p<0.001) for malnutrition. Among the cases, 16 (25.4%) fulfilled the Clinical Case Definition (CCD) for AIDS, compared to 2 (3.2%) among the controls. The adjusted Odds ratio for the difference in fulfilling the CCD for AIDS between cases and controls was statistically significant aOR of 10.383 with a 95% CI (2.275, 47.397; p<0.001). CONCLUSION: Primary pyomyositis is a common health problem in Northern Uganda. It is evident that malnutrition is the most common risk factor in Primary pyomyositis especially among the above thirteen year olds in Northern Uganda.

Metastatic colorectal carcinoma mimicking primary ovarian carcinoma presenting as 'giant' ovarian tumors in an individual with probable Lynch syndrome: a case report.

INTRODUCTION: Ovarian metastases occur in 3 to 8% of women with primary colon cancer. In the setting of a pre-existing colorectal carcinoma this would constitute a hereditary non-polyposis colorectal cancer, Lynch 2 syndrome, accounting for 5 to 10% of colon cancer cases. We unveil a case of 'giant' ovarian tumors mimicking primary ovarian cancer; ostensibly the first reported in East Africa. CASE PRESENTATION: A 58-year-old African woman was diagnosed with colorectal adenocarcinoma in June 2009. She had a right hemicolectomy with the tumor staged as regional cancer, following histopathological examination. Chemotherapy was administered both adjuvantly and 1 year later for what was thought to be a recurrence of tumor. Despite this, her general condition deteriorated. Following re-evaluation and an exploratory laparotomy she was found to have bilateral 'giant' ovarian tumors, with peritoneal seedlings and subcutaneous metastases (colonic in origin). A bilateral salpingo-oophorectomy was done, accompanied by histopathological analysis with institution of chemotherapy for ovarian cancer. Following immunohistochemistry tests and microsatellite instability analysis it was found that the ovarian tumors were secondaries from the colon. She was also identified as a Lynch syndrome case or a case of sporadic microsatellite instability, although with no suggestive family cancer history. The treatment regimen was changed to suit metastatic disease. CONCLUSIONS: The case presents a diagnostic and thus treatment conundrum. Two primary tumors (suspected Lynch syndrome) had been perceived yet there is actually only metastatic colorectal cancer. We also have a rare and unusual metastatic presentation: 'giant' bilateral ovarian tumors and subcutaneous nodules, concurrently. Further still, she is a case of probable Lynch syndrome, requiring genetic analysis for definitive classification and surveillance for hereditary non-polyposis colorectal cancer-associated cancers.Important inferences are drawn. Firstly, 'giant' ovarian tumors diagnosed as primary ovarian cancer may actually be colonic secondaries. Secondly, immunohistochemistry and microsatellite instability analysis tests ought to be part of the diagnostic package in colon cancer management, particularly for identifying tumor origin and the Lynch syndrome (a condition which has had little attention in resource-limited countries). Thirdly, multidisciplinary team collaboration is emphasized in colorectal cancer management.

Agreement between diagnoses of childhood lymphoma assigned in Uganda and by an international reference laboratory.

BACKGROUND: Correct diagnosis is key to appropriate treatment of cancer in children. However, diagnostic challenges are common in low-income and middle-income countries. The objective of the present study was to assess the agreement between a clinical diagnosis of childhood non- Hodgkin lymphoma (NHL) assigned in Uganda, a pathological diagnosis assigned in Uganda, and a pathological diagnosis assigned in The Netherlands. METHODS: The study included children with suspected NHL referred to the Mulago National Referral Hospital, Kampala, Uganda, between 2004 and 2008. A clinical diagnosis was assigned at the Mulago National Referral Hospital, where tissue samples were also obtained. Hematoxylin and eosin-stained slides were used for histological diagnosis in Uganda, and were re-examined in a pathology laboratory in The Netherlands, where additional pathological, virological and serological testing was also carried out. Agreement between diagnostic sites was compared using kappa statistics. RESULTS: Clinical and pathological diagnoses from Uganda and pathological diagnosis from The Netherlands was available for 118 children. The agreement between clinical and pathological diagnoses of NHL assigned in Uganda was 91% (95% confidence interval [CI] 84-95; kappa 0.84; P < 0.001) and in The Netherlands was 49% (95% CI 40-59; kappa 0.04; P = 0.612). When Burkitt's lymphoma was considered separately from other NHL, the agreement between clinical diagnoses in Uganda and pathological diagnoses in Uganda was 69% (95% CI 59-77; kappa 0.56; P < 0.0001), and the corresponding agreement between pathological diagnoses assigned in The Netherlands was 32% (95% CI 24-41; kappa 0.05; P = 0.326). The agreement between all pathological diagnoses assigned in Uganda and The Netherlands was 36% (95% CI 28-46; kappa 0.11; P = 0.046). CONCLUSION: Clinical diagnosis of NHL in Uganda has a high probability of error compared with pathological diagnosis in Uganda and in The Netherlands. In addition, agreement on the pathological diagnosis of NHL between Uganda and The Netherlands is very low.

HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study.

BACKGROUND: While the association of human papillomavirus (HPV) with cervical cancer is well established, the influence of HIV on the risk of this disease in sub-Saharan Africa remains unclear. To assess the risk of invasive cervical carcinoma (ICC) associated with HIV and HPV types, a hospital-based case-control study was performed between September 2004 and December 2006 in Kampala, Uganda. Incident cases of histologically-confirmed ICC (N=316) and control women (N=314), who were visitors or care-takers of ICC cases in the hospital, were recruited. Blood samples were obtained for HIV serology and CD4 count, as well as cervical samples for HPV testing. HPV DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 technique which detects all mucosal HPV types by DEIA and identifies 25 HPV genotypes by LiPA version 1. Samples that tested positive but could not be genotyped were designated HPVX. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression, adjusting for possible confounding factors. RESULTS: For both squamous cell carcinoma (SCC) and adenocarcinoma of the cervix, statistically significantly increased ORs were found among women infected with HPV, in particular single HPV infections, infections with HPV16-related types and high-risk HPV types, in particular HPV16, 18 and 45. For other HPV types the ORs for both SCC and adenocarcinoma were not statistically significantly elevated. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk in our study population. Among women infected with high-risk HPV types, no association between HIV and SCC emerged. However, an inverse association with adenocarcinoma was observed, while decrease in CD4 count was not associated with ICC risk. CONCLUSIONS: The ORs for SCC and adenocarcinoma were increased in women infected with HPV, in particular single HPV infections, infections with HPV16- and 18-related types, and high-risk HPV types, specifically HPV16, 18 and 45. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk, but among women infected with high-risk HPV types there was an inverse association between HIV infection and adenocarcinoma risk. These results suggest that HIV and CD4 count may have no role in the progression of cervical cancer.

The usefulness of immunohistochemistry in tissue microarrays of Human Papillomavirus negative adenocarcinoma of the uterine cervix.

BACKGROUND: The origin of adenocarcinomas presenting on the cervix uteri may be doubtful, i.e. whether it is of cervical or endometrial origin, due to the overlapping morphological features. In HPV negative samples, further tests may be needed to ascertain the nature of the tumours. We aimed to explore the use of immunohistochemistry profiles in tissue microarrays in archived samples of adenocarcinoma (ADC) of the cervix from Uganda that tested negative for HPV DNA. FINDINGS: Five commercially available antibodies were tested in tissue array sections immunostained utilizing the avidin-biotin (AB) technique. In 26 ADC samples, HPV was detected in 13, p16 in 15 (8 in HPV positive and 7 in HPV negative), CEA in 12, vimentin in 6, ER in 0, and PR in 2. Among the 13/25 HPV negative ADC samples, five were positive for CEA suggesting endocervical origin, and three were vimentin positive (one had a mucinous endocervical histological pattern and two were ADC, not otherwise specified, most likely of endometrial origin). CONCLUSIONS: The immunoprofiles of ADC with the antibodies studied are rather nonspecific. By using immunohistochemistry in 13 HPV negative ADC, endocervical tumour origin was suspected in five CEA positive cases while two out of three vimentin positive samples were probably of endometrial origin, suggesting that CEA and vimentin may be valuable in distinguishing HPV negative cervical adenocarcinomas from endometrial adenocarcinomas.

Comparison of human papillomavirus detection between freshly frozen tissue and paraffin embedded tissue of invasive cervical cancer.

BACKGROUND: Human Papillomavirus (HPV) detection results comparing paraffin embedded cervical tissue and other cervical specimens have been done with varying degrees of agreement. However, studies comparing freshly frozen specimens and paraffin embedded specimens of invasive cervical carcinomas are lacking. The aim of the study was to compare HPV detection using SPF10 broad-spectrum primers PCR followed by DEIA and genotyping by LiPA25 (version 1) between freshly frozen cervical tissue samples and paraffin embedded blocks of cervical tissue from the same patient. There were 171 pairs of paraffin embedded and freshly frozen samples analyzed from cervical carcinoma cases from Kampala, Uganda. RESULTS: 88.9% (95% CI: 83.2%-93.2%) of paraffin embedded samples were HPV positive compared with 90.1% (95% CI: 84.6%-94.1%) of freshly frozen samples, giving an overall agreement in HPV detection between fresh tissue and paraffin embedded tissue at 86.0% (95% CI: 79.8%-90.8%). Although the proportion of HPV positive cases in freshly frozen tissue was higher than those in paraffin blocks, the difference was not statistically significant (p > 0.05). In both types of tissues, single HPV infections were predominant, with HPV16 accounting for 47% of positive cases. Comparison in the overall agreement, taking into accounts not only positivity in general, but also HPV types, showed a 65% agreement (complete agreement of 59.7%, partial agreement of 5.3%) and complete disagreement of 35.0%. HPV detection in squamous cell carcinomas (SCC) and adenocarcinomas (ADC) was similar in fresh tissue or paraffin blocks (p ≥ 0.05).p16 immunostaining in samples that had at least one HPV negative results showed that 24 out of 25 cases had an over-expressed pattern. CONCLUSIONS: HPV DNA detection was lower among ADC as compared to SCC. However, such differences were minimized when additional p16 testing was added, suggesting that the technical issues may largely explain the HPV negative cases.

p53 expression in colorectal carcinoma in relation to histopathological features in Ugandan patients.

BACKGROUND: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular pathogenesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and reduced survival in patients. OBJECTIVE: This was a retrospective laboratory based study carried out in the Department of Pathology Makerere University, Kampala, Uganda. The aim of the study was to evaluate the expression of p53 protein in colorectal carcinoma in Ugandan patients, specifically its association with histological types, degree of differentiation, sites of the tumor and demographic characteristics of the patients. METHODS: Immunohistochemistry was carried out on 109 patient's paraffin embedded tissue blocks of colorectal carcinoma diagnosed in the Pathology Department, Faculty of Medicine Makerere University Kampala during the period 1995 to 2005. The indirect immunoperoxidase method using monoclonal antibody p53 DO-7 and Envision (+) Dual link system-HRP to detect p53 expression was used. Haematoxylin and eosin stain was used for evaluation of histological types and degree of differentiation of the tumors. Topography of the tumors and demographic data were obtained from accompanying histological request forms. RESULTS: Out of 109 patient's tissue blocks that were studied, 61 cases (56%) expressed p53 protein in the nucleus of malignant cells. Right sided colonic tumors were commoner (53.2%) than left sided colonic tumors (46.8%). p53 protein was expressed more in left sided colonic tumors with a significant difference (p<0.05), it was also expressed more in well differentiated tumors and non mucinous adenocarcinomas but with no significant difference (p>0.05). p53 expression was not affected by age or sex. CONCLUSION: Frequency of p53 protein expression in Ugandan patients did not differ from that reported in the other parts of the world. It was expressed more in the left sided colonic tumors and this could support the hypothesis that right and left colonic tumors could have different pathogenesis and probably also responsible for difference in prognosis in these two topographic sites.

Factors associated with carcinoma of the oesophagus at Mulago Hospital, Uganda.

BACKGROUND: In Uganda, as in many other parts of the world cancer of the oesophagus (CAE) is on the rise. Squamous cell carcinoma and adenocarcinoma are the common subtypes. Risk factors for this cancer have been identified but not studied systematically in Uganda. Identification of these factors would enable establishment of preventive measures. OBJECTIVE: To determine the prevalence, histological features and associated factors for CAE among patients referred to the endoscopic unit of Mulago hospital, Kampala, Uganda. METHODS: We performed a 1-year cross-sectional study in 2004 and 2005 of all patients presenting for oesophageal-gastro-duodenoscopy (EGD) at Mulago Hospital. Demographic characteristics, behavioural practices, endoscopy findings and histology results where biopsies were performed were collected using a study tool. Data analysis was done using STATA 8 statistical package. RESULTS: Two hundred nineteen patients were enrolled in the study, three were excluded because they could not tolerate the endoscopy procedure. Fifty five (19%) of the 287 had histologically proven CAE. Squamous cell carcinoma was found in 100% of tumours of the upper third, 91% middle third, and 73% lower third of the oesophagus. Four patients had a histological diagnosis of adenocarcinoma of the oesophagus. Factors that were associated with CAE included age (OR 1.63, CI 1.34-1.98, p value <0.001), smoking (OR 3.63, CI 1.82-7.23, p value <0.001) and gender (OR 2.17, CI 1.07-4.41, p value 0.032). CONCLUSION: Many patients referred for EGD in Uganda had esophageal cancer most of which were.squamous cell type. Smoking, male gender and older age were risk factors. Preventive measures should target stopping smoking.

Papillary squamous cell carcinoma of the cervix in Uganda: a report of 20 cases.

BACKGROUND: Non-glandular papillary carcinoma of the cervix are uncommon tumours. In Uganda where cervical carcinoma is very common, no cases of papillary squamous cell carcinoma of the cervix has been reported. OBJECTIVES: To ascertain the occurrence and describe the clinicopathological features of papillary squamous cell carcinoma of the cervix in Uganda. STUDY DESIGN: Retrospective review of histologically diagnosed cases of squamous cell carcinoma of cervix with papillary structures. METHODS: Retrospective review of cases of cervical carcinoma diagnosed in the Pathology Department, Makerere University from 1968 to 1973 was done. Cases with features of squamous differentiation and forming papillary pattern were then selected. RESULTS: Twenty cases were encountered and the ages of the patients ranged from 22 to 70 years (mean 46.6 years). Histologically, the tumours had thin to broad fibrovascular cores covered by multilayered squamous epithelium. In five cases, there were areas with very delicate fibrovascular cores covered by monolayered epithelial cells. CONCLUSION: The results of this study show that in Uganda, papillary squamous cell carcinoma of the cervix does occur and is predominantly a disease of older women. The results also confirm that papillary squamous cell carcinoma is a distinct subtype with some variants, and support the hypothesis that squamous cell carcinoma of the cervix is heterogeneous group of tumuors.