Scientists have uncovered the oldest evidence of a cancer-causing virus in humans, detecting fragments of human papillomavirus type 16, or HPV16, in the genome of a 45,000-year-old Homo sapiens from Siberia.
The virus, known today for causing most cases of cervical cancer and a growing number of throat and other cancers, was also found in the famous 5,300-year-old Ötzi the Iceman from the Alps. Researchers pieced together viral DNA from ancient genome data originally sequenced for studies on human evolution, not viruses. By mapping short DNA fragments to modern HPV references and checking for signs of ancient damage — such as chemical changes that occur over millennia — they confirmed that the sequences were genuine and not modern contaminants.
HPV16 comes in several lineages, with the A lineage being the most common and dangerous today. The ancient samples both carried versions of this A lineage, the team reports in a bioRxiv preprint study. That pushes the virus’s history in modern humans back to the Upper Paleolithic era, long before farming or cities.
Modern HPV16 spreads through skin-to-skin contact, often sexually, and infects cells in the skin or mucous membranes. In rare cases, it persists and drives cells to multiply out of control, leading to cancer. But viruses like this have likely coexisted with humans and our ancestors for millions of years, evolving alongside us.
The discovery challenges a popular idea that the A lineage jumped to modern humans from Neanderthals during interbreeding around 40,000 to 60,000 years ago. Earlier work on Neanderthal DNA found a different papillomavirus, not HPV16. Instead, the new evidence suggests HPV16 was already circulating in early modern human groups as they spread out of Africa into Eurasia.
“Our study presents the earliest molecular evidence of HPV16 in anatomically modern humans (AMHs), pushing back its evolutionary history and challenging the idea that HPV16A entered Homo sapiens through Neanderthal interbreeding,” the researchers write. “Our results suggest that HPV16 was already present in modern humans during the Upper Paleolithic, indicating a long-standing host–virus association independent of Neanderthal transmission.”
Journal Reference: J. Yazigi et al. Oncogenic HPV types identified in Paleolithic and Chalcolithic human genome sequencing data from Ust’-Ishim and Ötzi. bioRxiv doi: 10.64898/2025.12.14.694221
