HPV diversity and host epigenetics changes associated with cervical cancer in the high HIV setting of Botswana: what we learned and new challenges

Background: Cervical cancer (CC) and HIV are an important global health problem. Human papillomavirus (HPV), HIV and host epigenetic changes (DNA methylation) are each responsible for a considerable burden of CC. This high burden is attributed to the existence of a syndemic (synergistic epidemic) between HIV and HPV. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high. Accurate knowledge of HPV diversity, HIV infection and host epigenetic changes associated with CC in sub-Saharan Africa may provide accurate understanding of the natural history of the disease in these contexts. Methods: HPV and HIV infection was performed using Abbott Real-Time assay while DNA methylation was assessed using methylation specific PCR. Results and Discussion: In Botswana, despite patients harboring multiple HPV strains, HPV-16 genotype is the most frequently discovered in women with pre-cancerous and cancer lesions, followed by HPV-18. Also HPV-16 in HIV-positive women with pre-cancerous lesions to cancer is between 45.0% and 47.7%, and between 4.5% and 26.1% for HPV-18. Moreover, since only a small fraction of HPV-infected lesions progresses to CC, several studies have indicated that in addition to HPV and HIV, host factors, specifically host epigenetic changes, play a role in CC. Again we show that in a cohort of CC patients there is strong association between CC and promoter gene methylation of tumor suppressing genes (RARB, CADM1, DAPK1 and PAX1) at cancer site. However, the presence of epigenetic changes at those genes appeared to be independent of HIV status among subjects with CC. Additionally in patients with CC the rate of promoter methylation observed was greater than 64% in all the genes studied. Analysis also showed a higher risk of CC according to the increased number of methylated promoter genes. Moreover, we found that CC stage was influenced by RARB and CADM1 hypermethylation, and HIV status. Conclusions: These studies, conducted in local laboratories from local scientist in collaboration with the University of Botswana, University of Pennsylvania and Botswana Harvard Health Partnership, highlight the need to better understand the role of HPV, HIV and methylation of host genes leading to CC progression in Botswana and elsewhere.