Systematic analysis of Kaposi's sarcoma (KS)-associated herpesvirus genomes from a KS case-control study in Cameroon: Evidence of dual infections but no association between viral sequence variation and KS risk.

In sub-Saharan Africa, Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic, and Kaposi's sarcoma (KS) is a significant public health problem. Until recently, KSHV genotype analysis was performed using variable gene regions, representing a small fraction of the genome, and thus the contribution of sequence variation to viral transmission or pathogenesis are understudied. We performed near full-length KSHV genome sequence analysis on samples from 43 individuals selected from a large Cameroonian KS case-control study. KSHV genomes were obtained from 21 KS patients and 22 control participants. Phylogenetic analysis of the K1 region indicated the majority of sequences were A5 or B1 subtypes and all three K15 alleles were represented. Unique polymorphisms in the KSHV genome were observed including large gene deletions. We found evidence of multiple distinct KSHV genotypes in three individuals. Additionally, our analyses indicate that recombination is prevalent suggesting that multiple KSHV infections may not be uncommon overall. Most importantly, a detailed analysis of KSHV genomes from KS patients and control participants did not find a correlation between viral sequence variations and disease. Our study is the first to systematically compare near full-length KSHV genome sequences between KS cases and controls in the same endemic region to identify possible sequence variations associated with disease risk.

The challenge of AIDS-related malignancies in sub-Saharan Africa.

BACKGROUND: With the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral treatments, an increased risk of cancer has been described in industrialized countries. The question is to determine what occurs now and will happen in the future in the low income countries and particularly in sub-Saharan Africa where more than two-thirds of all HIV-positive people live in the world. The objective of our paper is to review the link between HIV and cancer in sub-Saharan Africa, putting it in perspective with what is already known in Western countries. METHODS AND FINDINGS: Studies for this review were identified from several bibliographical databases including Pubmed, Scopus, Cochrane, Pascal, Web of Science and using keywords "HIV, neoplasia, epidemiology and Africa" and related MesH terms. A clear association was found between HIV infection and AIDS-classifying cancers. In case-referent studies, odds ratios (OR) were ranging from 21.9 (95% Confidence Interval (CI) 12.5-38.6) to 47.1 (31.9-69.8) for Kaposi sarcoma and from 5.0 (2.7-9.5) to 12.6 (2.2-54.4) for non Hodgkin lymphoma. The association was less strong for invasive cervical cancer with ORs ranging from 1.1 (0.7-1.2) to 1.6 (1.1-2.3), whereas ORs for squamous intraepithelial lesions were higher, from 4.4 (2.3-8.4) to 17.0 (2.2-134.1). For non AIDS-classifying cancers, squamous cell conjunctival carcinoma of the eye was associated with HIV in many case-referent studies with ORs from 2.6 (1.4-4.9) to 13.0 (4.5-39.4). A record-linkage study conducted in Uganda showed an association between Hodgkin lymphoma and HIV infection with a standardized incidence ratio of 5.7 (1.2-17) although OR in case-referent studies ranged from 1.4 (0.7-2.8) to 1.6 (1.0-2.7). Other cancer sites found positively associated with HIV include lung, liver, anus, penis, vulva, kidney, thyroid and uterus and a decreased risk of female breast cancer. These results so far based on a relatively small number of studies warrant further epidemiological investigations, taking into account other known risk factors for these tumors. CONCLUSION: Studies conducted in sub-Saharan Africa show that HIV infection is not only strongly associated with AIDS-classifying cancers but also provided some evidence of association for other neoplasia. African countries need now to implement well designed population-based studies in order to better describe the spectrum of AIDS-associated malignancies and the most effective strategies for their prevention, screening and treatment.