Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV positive (HIV+) patients. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population to date. We characterized 118 tumors from Ugandan patients, of which 72 were HIV+, and performed extended mutation analysis on an additional 89 cases. We detected human papillomavirus (HPV) clade-specific differences in tumor DNA methylation, promoter- and enhancer-associated histone marks, gene expression and pathway dysregulation. Histone modification changes at HPV integration events were correlated with upregulation of nearby genes and endogenous retroviruses.