[Show abstract][Hide abstract] ABSTRACT: The quadrivalent HPV vaccine is highly effective in primary prevention of anogenital warts (AGWs). However, there is lack of systematic review in the literature of the epidemiology of AGWs in Sub Saharan Africa (SSA).
To review the prevalence, incidence and risk factors for AGWs in SSA prior to the introduction of HPV vaccination programs.
PubMed/MEDLINE, Africa Index Medicus and HINARI websites were searched for peer reviewed English language published medical literature on AGWs from January 1, 1984 to June 30, 2012. Relevant additional references cited in published papers were also evaluated for inclusion. For inclusion, the article had to meet the following criteria (1) original studies with estimated prevalence and/or incidence rates among men and/or women (2) detailed description of the study population (3) clinical or self-reported diagnosis of AGWs (4) HPV genotyping of histologically confirmed AGWs. The final analysis included 40 studies. Data across different studies were synthesized using descriptive statistics for various subgroups of females and males by geographical area. A meta - analysis of relative risk was conducted for studies that had data reported by HIV status.
The prevalence rates of clinical AGWs among sex workers and women with sexually transmitted diseases (STDs) or at high risk of sexually transmitted infection (STIs) range from 3.3% - 10.7% in East, 2.4% - 14.0% in Central and South, and 3.5% - 10.5% in West African regions. Among pregnant women, the prevalence rates range from 0.4% - 3.0% in East, 0.2% - 7.3% in Central and South and 2.9% in West African regions. Among men, the prevalence rates range from 3.5% - 4.5% in East, 4.8% - 6.0% in Central and South and 4.1% to 7.0% in West African regions. In all regions, the prevalence rates were significantly higher among HIV+ than HIV- women with an overall summary relative risk of 1.62 (95% CI: 143--1.82).The incidence rates range from 1.1 -- 2.7 per 100 person-years among women and 1.4 per 100 person years among men. Incidence rate was higher among HIV+ (3.0 per 100 person years) and uncircumcised men (1.7 per 100 person-years) than circumcised men (1.3 per 100 person-years).HIV positivity was a risk factor for AGWs among both men and women. Other risk factors in women include presence of abnormal cervical cytology, co-infection with HPV 52, concurrent bacteria vaginoses and genital ulceration. Among men, other risk factors include cigarette smoking and lack of circumcision.
AGWs are common among selected populations particularly HIV infected men and women. However, there is need for population-based studies that will guide policies on effective prevention, treatment and control of AGWs.
[Show abstract][Hide abstract] ABSTRACT: This article reviews the existing realities in Uganda to identify opportunities and potential obstacles of providing universal routine HPV vaccination to young adolescent girls. Cervical cancer is a public health priority in Uganda where it contributes to about 50--60% of all female malignancies. It is associated with a dismal 5-year relative survival of approximately 20%. With adequate financial resources, primary prevention through vaccination is feasible using existing education and health infrastructure. Cost-effectiveness studies show that at a cost of US$2 per dose, the current vaccines would be cost effective. With optimal (>=70%) coverage of the target population, the lifetime risk of cervical cancer could be reduced by >50%. Uganda fulfils 4 out of the 5 criteria set by the WHO for the introduction of routine HPV vaccination to young adolescent girls. The existing political commitment, community support for immunization and the favorable laws and policy environment all provide an opportunity that should not be missed to introduce this much needed vaccine to the young adolescent girls. However, sustainable financing by the government without external assistances remains a major obstacle. Also, the existing health delivery systems would require strengthening to cope with the delivery of HPV vaccine to a population that is normally not targeted for routine vaccination. Given the high incidence of cervical cancer and in the absence of a national screening program, universal HPV vaccination of Ugandan adolescent girls is critical for cervical cancer prevention.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: Burkitt's lymphoma (BL) is a major cause of death among Ugandan children. We studied clinical characteristics and outcomes of childhood BL over time at the Uganda Cancer Institute (UCI). A total of 1217 children (766 boys, 451 girls, mean age 6.69 years) diagnosed with BL between 1985 and 2005 were included. There were no significant changes in the proportion of boys and girls diagnosed, or in mean age at diagnosis. Facial tumor (n=945, 77.65%) and abdominal disease (n=842, 69.19%) were the most common presentations. The proportion of children presenting with hepatic mass, malignant pleocytosis, and advanced-stage (stage C and D) BL increased during the study period (P<0.01). A total of 1085 children out of 1206 (89.97%) received at least one cycle of chemotherapy, and 832 of 1099 (75.71%) demonstrated objective response (i.e. complete or partial remission). The most common symptoms at BL diagnosis were fever (n=621, 51.03%), anemia (n=593, 48.73%), and weight loss (n=588, 48.32%). Significant increases in the proportion of children with fever, and significant changes in the proportion of children with anemia, night sweats and severe infection were observed. HIV positivity was 3.87%, but no substantial differences in the proportion of HIV-positive children were observed. Mortality was not significantly different over time: it was similar in boys and girls, higher in older children (compared with younger ones), in those with advanced-stage BL, and HIV-positive children, but lower in children with facial tumors compared with other tumor presentations, and among those who received chemotherapy.
Transactions of the Royal Society of Tropical Medicine and Hygiene 10/2011; 105(12):717-26. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To understand the prospects for human papillomavirus (HPV) mass vaccination in the setting of a developing country, we studied the co-occurrence of seropositivity to multiple high-risk (hr) HPV types among HIV-positive and HIV-negative Ugandan women. Our seroepidemiological study was conducted among 2053 women attending antenatal clinics. Sera were analysed for antibodies to eight hrHPV types of the α-7 (18/45) and α-9 (16/31/33/35/52/58) species of HPV by using a multiplex serology assay. Our results show that seropositivity for greater than one hrHPV type was as common (18 %) as for a single type (18 %). HIV-positive women had higher HPV16, HPV18 and HPV45 seroprevalences than HIV-negative women. In multivariate logistic regression analysis, age (>30 years) and level of education (secondary school and above) reduced the risk, whereas parity (>5) and HIV-positivity increased the risk for multiple hrHPV seropositivity. However, in stepwise logistic regression analyses, HIV-status remained the only independent, stand-alone risk factor [odds ratio (OR) 1.7, 95 % confidence interval (CI) 1.0-2.8). On the other hand, the risk of HPV16 or HPV18 seropositive women, as compared to HPV16 or HPV18 seronegative women, for being seropositive to other hrHPV types was not significantly different when they were grouped by HIV-status (ORHPV16/HIV+ 12, 95 % CI 4.5-32 versus ORHPV16/HIV- 22, 95 % CI 15-31 and ORHPV18/HIV+ 58, 95 % CI 14-242 versus ORHPV18/HIV- 45, 95 % CI 31-65). In conclusion, seropositivity to HPV16, HPV18 and to non-vaccine hrHPV types is common in Ugandan women, suggesting that there is little natural cross-protective immunity between the types. HIV-positivity was an independent, stand-alone, albeit moderate risk factor for multiple hrHPV seropositivity. HPV mass vaccination may be the most appropriate method in the fight against cervical cancer in the Ugandan population.
Journal of General Virology 08/2011; 92(Pt 12):2776-83. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Low avidity of antibodies against viral, bacterial and parasitic agents has been used for differential diagnosis of acute versus recent/past infections. The low-avidity antibodies may however, persist for a longer period in some individuals.
We studied the association of human papillomavirus (HPV) type 16 antibody avidity with seroprevalence to HPV types 6/11/18/31/33/45. Antibody avidity was analysed for 365 HPV16 seropositive pregnant Finnish and Ugandan women using a modified ELISA.Low avidity of HPV16 antibodies was found in 15% of Finnish and 26% of Ugandan women. Ugandan women with low-avidity HPV16 antibodies had an increased risk estimate for HPV6/11 (odds ratio, OR 2.9; 95%CI 1.01-8.4) seropositivity but not to high-risk HPV types 18/31/33/45.
Association of the low avidity HPV16 antibody "phenotype" with possible susceptibility to infections with other HPV types warrants investigation.
[Show abstract][Hide abstract] ABSTRACT: While infections with human papillomavirus (HPV) are highly prevalent among sexually active young women in Uganda, information on incidence, clearance and their associated risk factors is sparse. To estimate the incidence, prevalence and determinants of HPV infections, we conducted a prospective follow-up study among 1,275 women aged 12-24 years at the time of recruitment. Women answered a questionnaire and underwent a pelvic examination at each visit to collect exfoliated cervical cells. The presence of 42 HPV types was evaluated in exfoliated cervical cells by a polymerase chain based (PCR) assay (SPF10-DEIA LiPA).
Three hundred and eighty (380) of 1,275 (29.8%) women were followed up for a median time of 18.5 months (inter-quartile range 9.7-26.6). Sixty-nine (69) women had incident HPV infections during 226 person-years of follow-up reflecting an incidence rate of 30.5 per 100 person-years. Incident HPV infections were marginally associated with HIV positivity (RR = 2.8, 95% CI: 0.9 - 8.3). Clearance for HPV type-specific infections was frequent ranging between 42.3% and 100.0% for high- and 50% and 100% for low-risk types. Only 31.2% of women cleared all their infections. Clearance was associated with HIV negativity (Adjusted clearance = 0.2, 95% CI: 0.1 - 0.7) but not with age at study entry, lifetime number of sexual partners and multiplicity of infections. The prevalence of low-grade squamous intraepithelial lesions (LSILs) was 53/365 (14.5%). None of the women had a high-grade cervical lesion (HSIL) or cancer. Twenty-two (22) of 150 (14.7%) HPV negative women at baseline developed incident LSIL during follow-up. The risk for LSIL appeared to be elevated among women with HPV 18-related types compared to women not infected with those types (RR = 3.5, 95% CI: 1.0 - 11.8).
Incident HPV infections and type-specific HPV clearance were frequent among our study population of young women. These results underscore the need to vaccinate pre-adolescent girls before initiation of sexual activity.
[Show abstract][Hide abstract] ABSTRACT: Although infections with multiple human papillomavirus (HPV) types have been reported widely, more information is needed on the occurrence of the different types. We determined the distribution of seroprevalences to multiple HPV types in Finland and Uganda to compare the epidemiology of the different HPV types in the 2 populations. Serum samples were obtained from 2784 Finnish and 1964 Ugandan women (mean ages 22 y and 25 y, respectively) of whom 44% and 57%, respectively, had antibodies to at least 1 of the 7 HPV types (6, 11, 16, 18, 31, 33, 45) tested (p < 0.001). Multiple HPV antibody positivity was common. HPV45-seropositive Finns had a higher risk of having antibodies to other high-risk HPV types: HPV18 (odds ratio (OR) = 10.9), HPV31 (OR 6.1), HPV33 (OR 12.2), than their Ugandan counterparts: HPV18 (OR 3.4), HPV31 (OR 2.2), HPV33 (OR 3.3). Increased estimates for being double antibody-positive were also noted among HPV18- and HPV16-seropositive women, but there were no major differences between HPV16-seropositive Finns and Ugandans. In addition to biological and behavioural factors, iatrogenic and societal factors (screening vs no screening) may also result in the different occurrence of infections with the high-risk HPV types in Finland and Uganda.
[Show abstract][Hide abstract] ABSTRACT: The proportion of women who have already been exposed to human papillomavirus (HPV) infection by the time they first become pregnant, and the influence of pregnancy and delivery on the course of HPV infection are unclear. In Kampala, Uganda, 987 young primiparous pregnant women aged <25 years had gynaecological examination and liquid-based cytology. In the follow-up, women acted as their own controls, i.e., 1st/2nd versus 3rd trimesters (105 women), and during pregnancy versus after delivery (289 women). HPV was assessed using highly sensitive PCR assays. Prevalence of HPV and HIV infections at baseline were 60.0% and 7.3%, respectively. HPV16 and 18 were detected in 8.4% and 5.8%, respectively, i.e., less frequently than HPV51 (8.7%) and 52 (12.1%). At follow-up new HPV infections were detected in 42.9% of women between the 1st/2nd and 3rd trimesters, and 38.1% between pregnancy and delivery, but 50.4% and 71.8% of HPV infections, respectively, cleared, leaving HPV prevalence unchanged in the different periods. Prevalence of cytological abnormalities diminished after delivery (from 21.2% to 12.4%). Presence of genital warts and sexually transmitted infections other than HPV were the strongest risk factors for prevalent or incident HPV infection. Clearance was lower among HIV-positive women. In conclusion, HPV prevalence was high in primiparous women in Uganda, but pregnancy did not seem to be a period of special vulnerability to the infection.
International Journal of Cancer 12/2008; 123(9):2180-7. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before.
We reviewed records at Uganda Cancer Institute (UCI) for years 1994-2004, to compare clinical features and outcome of BL in children who are HIV positive and negative (HIV+, HIV-). As statistical methods we used Student's t-test, Chi-square and Kaplan-Meier's to compare both groups.
Of 1,462 records of children retrieved, 228 met the eligibility criteria and were reviewed (158 HIV-, 70 HIV+). There were 139 (61%) males and 89 (39%) females. The mean age was 6.9 years (HIV+ 6.7, HIV- 7.1). One hundred seventy-one cases (75%) had facial tumor (HIV+ 71.4%, HIV- 76.6%). HIV positive children presented significantly with extrafacial disease (lymphadenopathy 67%, hepatic masses 51%, and thoracic masses 10%). Presentation with advanced stage disease occurred more frequently in HIV positive patients compared to HIV negative patients. Treatment response rates to chemotherapy were similar irrespective of HIV status. However, overall survival was poorer in HIV positive patients with a median survival of 11.79 months (P-value < 0.000, 95% CI 8.65-14.92).
BL in Uganda presents frequently with facial disease irrespective of HIV status. However HIV+ BL also presents commonly with extra facial sites, mainly lymphadenopathy. There is no difference in response to treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is need for further characterization of BL in Uganda to understand the role of HIV in disease process and outcome.
Pediatric Blood & Cancer 10/2008; 52(4):455-8. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Information on the prevalence of cervical infection with different human papillomavirus (HPV) types among young women is essential to support the introduction of HPV vaccine in Uganda.
Cross-sectional findings are presented from a cohort study of 1,275 sexually active women aged 12-24 years seeking health services at a clinic for teenagers in Kampala, Uganda. We assessed the presence of 39 HPV types by use of highly sensitive polymerase chain reaction assays.
The prevalence of HPV infection was 74.6%, and the prevalence of human immunodeficiency virus infection was 8.6%. High-risk HPV types were found in 51.4% of women, and the most frequently detected high-risk types were, in decreasing order, HPV 52, 51, 18, and 16. A total of 71.8% of the women who were positive for HPV 16 and/or 18 were also infected with other high-risk HPV types. HIV-positive women had a higher prevalence of HPV infection (87.8% vs 73.2%) and of multiple-type infections (64.6% vs 37.3%), compared with HIV-negative women. Employment in the tertiary sector, lifetime number of sexual partners, concurrent pregnancy, and the presence of genital warts were significantly associated with HPV positivity.
The prevalence of HPV infection is high among young women in Kampala, Uganda. Clinics for teenagers provide an opportunity to monitor the impact of HPV vaccines and, possibly, to catch up unvaccinated young women who have recently become sexually active.
The Journal of Infectious Diseases 03/2008; 197(4):555-62. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Burkitt lymphoma, a childhood tumor common in parts of sub-Saharan Africa, has been directly associated with Epstein-Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case-control study of HIV-seronegative children (<or=15 years) admitted to hospital. Cases were diagnosed with Burkitt lymphoma and controls with non-malignant conditions or non-lymphatic cancers. Interviews were conducted and serological samples collected and, when possible, tested for both EBV and malaria. Adjusted odds ratios (ORs) for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, residential district, household income and tribe. The mean age of cases was 7 years and 61% were male. Compared to controls, cases were more likely to be reported having received more frequent treatment for malaria in the past year (OR = 2.0; p = 0.001) and less likely to be living in a home where insecticides were used (OR = 0.2; p < 0.0001). Odds ratios for Burkitt lymphoma in children increased with increasing antibody levels against EBV (p < 0.0001) and malaria (p = 0.05). Findings were similar for children residing in districts close to the capital city and in remote areas. Cases were 5 times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 5.0; p = 0.003). Our findings suggest that EBV and malaria may act synergistically in the pathogenesis of childhood Burkitt lymphoma. Malaria prevention measures may also prevent this childhood cancer.
International Journal of Cancer 03/2008; 122(6):1319-23. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We reviewed the scientific literature on Burkitt's lymphoma (BL) in Africa in order to provide information on the current status of clinical care and the existing research challenges. BL epidemiology led to the discovery of the Epstein Barr virus, an important cause of several viral illnesses and malignancies. The incidence of BL has increased in the endemic areas of Africa, overlapping with the epidemic of HIV and increase of malaria. The impact of this on the clinical care of BL in the region is therefore of interest, especially in HIV-infected children. Rapid methods must be developed which enable the correct diagnosis to be made. It is important to improve supportive care to allow fairly aggressive treatment, to research into salvage therapy for those who fail first-line treatment, and to develop less toxic drug combinations for HIV-infected patients. Documentation of HIV status through counselling should be offered to all patients.
Tropical Doctor 02/2008; 38(1):7-11. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of an epidemiological study of cancer in Uganda, we investigated social, sexual and reproductive factors in relation to the risk of cancer of the uterine cervix. Patients with all cancer types or with benign tumours were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against the human immunodeficiency virus-1 (HIV). The case-control study reported here involves 702 HIV-seronegative women, 343 of whom were diagnosed with cancer of the uterine cervix. Key findings were that the risk of cervical cancer increased linearly with the number of pregnancies [chi2(1)=44.7; P<0.0001]; a woman reporting having had 10 or more children had a roughly seven-fold increase in risk of the tumour as compared with women reporting fewer than four pregnancies (odds ratio=7.1; 95% confidence interval 3.8-13.2). The risk also varied inversely with age at first reported sexual intercourse [chi2(1)=8.4; P=0.004], perhaps reflecting an earlier age of infection with human papillomavirus, the main causal agent. These results are in line with those reported from studies in other countries.
European Journal of Cancer Prevention 12/2007; 16(6):555-8. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Burkitt's lymphoma (BL) was first described in Eastern Africa, initially thought to be a sarcoma of the jaw. Shortly it became well known that this was a distinct form of Non Hodgkin's lymphoma. The disease has given insight in all aspects of cancer research and care. Its peculiar epidemiology has led to the discovery of Epstein Barr virus (EBV) and its importance in the cause of several viral illnesses and malignancies. The highest incidence and mortality rates of BL are seen in Eastern Africa. BL affects mainly children, and boys are more susceptible than girls. Evidence for a causal relationship between EBV and BL in the endemic form is fairly strong. Frequency of association between EBV and BL varies between different patient groups and different parts of the world. EBV may play a role in the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal translocation. Although several studies suggest an association between malaria and BL, there has never been a conclusive population study in support of a direct role of malaria in causation of BL. The emergence of HIV and a distinct subtype of BL in HIV infected have brought a new dimension to the disease particularly in areas where both HIV and BL are endemic. BL has been reported as a common neoplasmin HIV infected patients, but not in other forms of immuno-depression, and the occurrence of BL seems to be higher amongst HIV positive adults, while the evidence of an association amongst children is still disputed. The role of other possible risk factors such as low socio-economical status, exposure to a plant species common in Africa called Euphorbiaceae, exposure to pesticies and to other infections such as schistosomiasis and arbovirus (an RNA virus transmitted by insect vectors) remain to be elucidated.