Human papillomavirus (HPV)-positive cancer cells contain virus and host DNA and exhibit marked genome instability. In this issue of Cancer Discovery, Akagi and colleagues characterize the remarkably complex landscape of virus-host DNA molecules in HPV-positive cells, providing evidence for diverse integrated and extrachromosomal virus-host hybrid DNAs with the potential to drive clonal evolution. See related article by Akagi et al., p. 910 (4).
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