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Purpose of review Following our review of AIDS-associated cancer in developing nations in 2004, we sought to update recent publications and review data on the challenges and opportunities for the treatment and research of AIDS malignancies in Africa. Recent findings It is apparent that the burden of AIDS-related malignancies and other virus-associated tumors is significant and increasing in Africa. Several recent studies report findings on conjunctival squamous cell carcinoma and there is a report that Hodgkin's disease, a non-AIDS-defining neoplasm, is increasing in incidence. International collaborative partnerships dedicated to AIDS malignancies in developing countries are feasible and invaluable for clinical strategies to address this aspect of the pandemic. A departure point is the ongoing work of the East Africa – Case Western Reserve University Collaboration in AIDS malignancies. Summary The burden of neoplastic complications of HIV infection and endemic virus-associated tumors are assuming increasing significance in Africa. There is a need to develop nonmyelotoxic therapies and approaches that are hypothesis-driven and pathogenesis-based. The scarcity and shortages in this region demand that our scientific and therapeutic strategies are both suitable and pragmatic for testing in this setting. It is also imperative that African investigators lead us in this important endeavor.

Purpose: To build capacity in the resource-poor setting to support the clinical investigation and treatment of AIDS-related malignancies in a region of the world hardest hit by the AIDS pandemic. Methods: An initial MEDLINE database search for international collaborative partnerships dedicated to AIDS malignancies in developing countries failed to identify any leads. This search prompted us to report progress on our collaboration in this aspect of the epidemic. Building on the formal Uganda-Case Western Reserve University (Case) Research Collaboration dating back to 1987, established NIH-supported centers of research excellence at Case, and expanding activities in Kenya, scientific and training initiatives, research capital amongst our institutions are emerging to sustain a international research enterprise focused on AIDS and other viral-related malignancies. Results: A platform of clinical research trials with pragmatic design has been developed to further enhance clinical care and sustain training initiatives with partners in East Africa and the United States. An oral chemotherapy feasibility trial in AIDS lymphoma is near completion; a second lymphoma trial of byrostatin and vincristine is anticipated and a feasibility trial of indinavir for endemic Kaposi's sarcoma is planned. Conclusions: In the absence of published reports of evolving international partnerships dedicated to AIDS malignancy in resource constrained settings, we feel it important for such progress on similar or related international collaborative pursuits to be published. The success of this effort is realized by the long-term international commitment of the collaborating investigators and institutions to sustain this effort in keeping with ethical and NIH standards for the conduct of research; the provision of formal training of investigators and research personnel on clinical problems our East African partners are faced with in practice and the development of pragmatic clinical trials and therapeutic intervention to facilitate technology transfer and enhance clinical practice.

Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National Hospital, the national referral medical center in Nairobi, Kenya. To investigate the influence of human immunodeficiency virus (HIV) infection in adult BL in Kenya, we conducted a national prevalence survey of all patients 16 years of age and older with BL. A systematic review of medical records of all patients diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was based and confirmed on review of pathological material from time of original diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay (ELISA). Twenty-nine adult patients with BL were identified during the 5-year study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and the median age was 26 years. Nineteen patients (66%) with BL were HIV-seropositive. The proportion of men was similar in HIV-seropositive and -seronegative patients (58% vs 60%). HIV-seropositive BL patients were significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV-seropositive patients uniformly presented with constitutional or B symptoms and advanced BL accompanied by diffuse lymph node involvement, whereas the clinical presentation of HIV-seronegative patients during this time period was reminiscent of the “typical” endemic pattern of disease with complete sparing of peripheral lymph nodes. The overall survival of HIV-seropositive cases was significantly worse than that of the HIV-seronegative cases; median survival in the HIV-seropositive patients was 15 weeks. There is an approximate 3-fold increase in the incidence of adult BL during the time period of this study, which is attributable to the AIDS epidemic. In this setting, patients often present with disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter two of which heretofore have been commonly associated with non-lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually transmitted diseases in Kenya. These observations warrant inclusion of AIDS-related BL in the differential diagnosis of the adult patient with unexplained fever and lymphadenopathy in Kenya. The corollary is that HIV infection is virtually excluded in an adult patient without peripheral lymphadenopathy and biopsy-proven BL. © 2001 Wiley-Liss, Inc.

With the emergence of the highly active antiretroviral therapy era, it is apparent that the incidence of Kaposi sarcoma, in particular, and lymphoma in patients with AIDS is declining, especially in regions of the world where these regimens are routinely available. The burden of HIV infection and AIDS is greatest in the developing world, and no doubt neoplastic complications are increasingly encountered. The purpose of this review is to highlight recent developments of this aspect of the AIDS epidemic in the developing world.It was readily apparent that the incidence of Kaposi sarcoma sharply increased after the onset of the AIDS epidemic in developing countries. By the end of the second decade of the epidemic, non-Hodgkin lymphoma is increasing in incidence and the natural history of Burkitt lymphoma is evolving in the backdrop of HIV infection as well. Cervical cancer is the most common cancer in women in many developing countries, yet the true impact of HIV infection on the development of this neoplasm is not fully understood. Squamous cell carcinoma of the conjunctiva appears to be a unique AIDS-associated neoplasm that is encountered in sub-Saharan Africa as well. Finally, although the epidemiologic and clinicopathologic features for many AIDS-associated neoplasms are well characterized in developing regions of the world, there is a paucity of data on the therapeutic approach to these tumors in this setting.It is apparent that as the AIDS pandemic proceeds, the burden of neoplastic diseases is increasing in developing nations. Current therapeutic approaches are not well documented. Pragmatic prevention and therapeutic interventions suitable for the resource-constrained setting are clearly needed.

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. As we enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic, it is apparent that the evolution of antiretroviral therapy and the emergence of combination antiviral strategies have greatly affected the natural history of HIV infection and its neoplastic complications. For example, there may be a trend for declining incidence of AIDS-related lymphoma in the United States for the first time. However, in regions of the world where the burden of HIV infection is greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of morbidity and mortality. Treatment of lymphoma has evolved coincident with improvements in antiretroviral therapy. Infusional chemotherapy regimens may offer advantages over other regimens and schedules, but comparative trials have not been done. Clinical trial data are available on which to develop therapeutic strategies to treat this disease in East Africa where pragmatic approaches are needed. Both the differences in manifestations of HIV infection and the inherent difficulties in administering cytotoxic chemotherapy in this part of the world must be taken into consideration in planning therapeutic strategies. Improved understanding of the pathogenesis of HIV infection and lymphoma will likely yield improved therapeutic interventions as well.

Burkitt lymphoma (BL) is a B-cell tumor whose characteristic gene aberration is the translocation t(8;14), which determines c-myc overexpression. Several genetic and epigenetic alterations other than c-myc overexpression have also been described in BL. It has been demonstrated that the RBL2/p130 gene, a member of the retinoblastoma family (pRbs), is mutated in BL cell lines and primary tumors. The aim of this study was to investigate the biologic effect of RBL2/p130 in BL cells and its possible role in lymphomagenesis. Therefore, we reintroduced a functional RBL2/p130 in BL cell lines where this gene was mutated. Our results demonstrated that RBL2/p130-transfected cells regain growth control. This suggests that RBL2/p130 may control the expression of several genes, which may be important for cell growth and viability. Gene-expression analysis revealed a modulation of several genes, including CGRRF1, RGS1, BTG1, TIA1, and PCDHA2, upon RBL2/p130 reintroduction. We then monitored their expression in primary tumors of endemic BL as well, demonstrating that their expression resembled those of the BL cell lines. In conclusion, these data suggest that, as RBL2/p130 modulates the expression of target genes, which are important for cell growth and viability, its inactivation may be relevant for the occurrence of BL.