A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

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

A public health approach to cervical cancer screening in Africa through community-based self-administered HPV testing and mobile treatment provision.

The World Health Organization (WHO) refers to cervical cancer as a public health problem, and sub-Saharan Africa bears the world's highest incidence. In the realm of screening, simplified WHO recommendations for low-resource countries now present an opportunity for a public health approach to this public health problem. We evaluated the feasibility of such a public health approach to cervical cancer screening that features community-based self-administered HPV testing and mobile treatment provision. In two rural districts of western-central Uganda, Village Health Team members led community mobilization for cervical cancer screening fairs in their communities, which offered self-collection of vaginal samples for high-risk human papillomavirus (hrHPV) testing. High-risk human papillomavirus-positive women were re-contacted and referred for treatment with cryotherapy by a mobile treatment unit in their community. We also determined penetrance of the mobilization campaign message by interviewing a probability sample of adult women in study communities about the fair and their attendance. In 16 communities, 2142 women attended the health fairs; 1902 were eligible for cervical cancer screening of which 1892 (99.5%) provided a self-collected vaginal sample. Among the 393 (21%) women with detectable hrHPV, 89% were successfully contacted about their results, of which 86% returned for treatment by a mobile treatment team. Most of the women in the community (93%) reported hearing about the fair, and among those who had heard of the fair, 68% attended. This public health approach to cervical cancer screening was feasible, effectively penetrated the communities, and was readily accepted by community women. The findings support further optimization and evaluation of this approach as a means of scaling up cervical cancer control in low-resource settings

Using Media to Promote Public Awareness of Early Detection of Kaposi's Sarcoma in Africa.

BackgroundDespite its hallmark cutaneous presentation, most Kaposi's sarcoma (KS) in Africa is diagnosed too late for effective treatment. Early diagnosis will only be achievable if patients with KS present earlier for care. We hypothesized that public awareness about KS can be enhanced through exposure to common media.MethodsWe developed educational messages regarding early detection of KS for the general African public portraying a three-part theme: "Look" (regularly examine one's skin/mouth), "Show" (bring to the attention of a healthcare provider any skin/mouth changes), and "Test" (ask for a biopsy for definitive diagnosis). We packaged the messages in three common media forms (comic strips, radio, and video) and tested their effect on increasing KS awareness among adults attending markets in Uganda. Participants were randomized to a single exposure to one of the media and evaluated for change in KS-related knowledge and attitudes.ResultsAmong 420 participants, media exposure resulted in increased ability to identify KS (from 0.95% pretest to 46% posttest); awareness that anyone is at risk for KS (29% to 50%); belief that they may be at risk (63% to 76%); and knowledge that definitive diagnosis requires biopsy (23% to 51%) (all p < 0.001). Most participants (96%) found the media culturally appropriate.ConclusionExposure to media featuring a theme of "Look," "Show," and "Test" resulted in changes in knowledge and attitudes concerning KS among the general public in Uganda. High incidence and poor survival of KS in Africa are an impetus to further evaluate these media, which are freely available online

Using Media to Promote Public Awareness of Early Detection of Kaposi's Sarcoma in Africa.

Background:Despite its hallmark cutaneous presentation, most Kaposi's sarcoma (KS) in Africa is diagnosed too late for effective treatment. Early diagnosis will only be achievable if patients with KS present earlier for care. We hypothesized that public awareness about KS can be enhanced through exposure to common media. Methods:We developed educational messages regarding early detection of KS for the general African public portraying a three-part theme: "Look" (regularly examine one's skin/mouth), "Show" (bring to the attention of a healthcare provider any skin/mouth changes), and "Test" (ask for a biopsy for definitive diagnosis). We packaged the messages in three common media forms (comic strips, radio, and video) and tested their effect on increasing KS awareness among adults attending markets in Uganda. Participants were randomized to a single exposure to one of the media and evaluated for change in KS-related knowledge and attitudes. Results:Among 420 participants, media exposure resulted in increased ability to identify KS (from 0.95% pretest to 46% posttest); awareness that anyone is at risk for KS (29% to 50%); belief that they may be at risk (63% to 76%); and knowledge that definitive diagnosis requires biopsy (23% to 51%) (all p < 0.001). Most participants (96%) found the media culturally appropriate. Conclusion:Exposure to media featuring a theme of "Look," "Show," and "Test" resulted in changes in knowledge and attitudes concerning KS among the general public in Uganda. High incidence and poor survival of KS in Africa are an impetus to further evaluate these media, which are freely available online

Association Between Immunoglobulin E Levels and Kaposi Sarcoma in African Adults With Human Immunodeficiency Virus Infection.

It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)-infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS

The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi\u27s Sarcoma in Africa

Background—Other than Kaposi\u27s 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, IQR: 90 to190 nM/μM) than cases (110, IQR: 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% CI: 27% to 77%) in the odds of KS compared to 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

Understanding Diagnostic Delays for Kaposi Sarcoma in Kenya: A Qualitative Study.

BACKGROUND: Although HIV-associated Kaposi sarcoma (KS) is frequently diagnosed at an advanced stage in sub-Saharan Africa, reasons for diagnostic delays have not been well described. METHODS: We enrolled patients >18 years with newly diagnosed KS between 2016 and 2019 into the parent study, based in western Kenya. We then purposively selected 30 participants with diversity of disease severity and geographic locations to participate in semistructured interviews. We used 2 behavioral models in developing the codebook for this analysis: situated Information, Motivation, and Behavior framework and Andersen model of total patient delay. We then analyzed the interviews using framework analysis. RESULTS: The most common patient factors that delayed diagnosis were lack of KS awareness, seeking traditional treatments, lack of personal efficacy, lack of social support, and fear of cancer, skin biopsy, amputation, and HIV diagnosis. Health system factors that delayed diagnosis included previous negative health care interactions, incorrect diagnoses, lack of physical examination, delayed referral, and lack of tissue biopsy availability. Financial constraints were prominent barriers for patients to access and receive care. Facilitators for diagnosis included being part of an HIV care network, living near health facilities, trust in the health care system, desire to treat painful or disfiguring lesions, and social support. CONCLUSIONS: Lack of KS awareness among patients and providers, stigma surrounding diagnoses, and health system referral delays were barriers in reaching KS diagnosis. Improved public health campaigns, increased availability of biopsy and pathology facilities, and health provider training about KS are needed to improve early diagnosis of KS