The 5,300-year-old Ötzi the Iceman mummy and a prehistoric man who lived in Siberia 45,000 years ago both carried a cancer-causing strain of human papillomavirus (HPV), new research finds.
Scientists analyzed ancient genetic data previously collected from the individuals, and found that both were likely infected with HPV16, a preprint paper posted to bioRxiv on Dec. 16, reported. In the study, which has yet to undergo peer-review, the authors present what they say is the “earliest molecular evidence” of HPV16 in modern humans.
HPV in ancient humans
HPV encompasses a diverse family of viruses that are primarily transmitted through direct skin-to-skin or sexual contact, and they are commonly found in humans today. Most infections are symptomless but in a small fraction of cases, HPV16 and other high-risk types (known as “oncogenic” papillomaviruses) can fuel the development of some cancers.
While the clinical significance of papillomaviruses is well understood, little is known about their occurrence among prehistoric human populations. In the study, the authors explored a long-standing question of how far back cancer-linked papillomaviruses — particularly HPV16 — have circulated in modern humans, study co-author Marcelo Briones, a professor at the Center for Medical Bioinformatics at the Medical School of the Federal University of São Paulo, Brazil, told Live Science in an email.
“The results indicate that HPV16 has been associated with anatomically modern humans for a very long time, likely well before major population splits outside Africa,” or before 50,000 to 60,000 years ago, Briones said. “This supports the idea that oncogenic human papillomaviruses are not recent pathogens but long-term companions of their hosts, evolving alongside primates and humans over extended evolutionary timescales.”
The researchers re-analyzed publicly available genome sequencing datasets for both Ötzi and the Siberian man, known as Ust’-Ishim. These individuals were chosen because they represent two of the best-preserved and best-characterized ancient human genomes available, Briones said.
Ötzi is a naturally mummified man whose 5,300-year-old remains were discovered in 1991 high in the Alps mountain range on the Austria-Italy border. His remarkably well-preserved body, clothing and tools have since provided a rare glimpse into prehistoric life in the region. The Ust’-Ishim man, meanwhile, who was discovered in 2008, lived around 45,000 years ago in what is now western Siberia. His remains — a single leg bone — yielded one of the oldest modern human genomes ever to be fully sequenced.
Briones and colleagues searched the genetic datasets for DNA fragments matching known HPV genomes. They found multiple DNA fragments matching HPV16 (specifically, a lineage known as HPV16A) in both individuals, suggesting the virus was present in them.
Most previous hypotheses about when HPV16 emerged in modern humans relied on computer models of how the virus evolves over time. These suggest the virus has ancient evolutionary origins but lacked direct biological confirmation, according to the researcher. In general, computer models suggest that papillomaviruses likely co-evolved with vertebrates for hundreds of millions of years.
While the preprint does not address the ultimate origins of HPVs as a group, it does show at least one high-risk type was present in modern humans at least 45,000 years ago.
Given this early date, the new findings challenge a previously proposed hypothesis that Neanderthals transmitted HPV16A to prehistoric Homo sapiens populations through interbreeding, Briones said. Although he said the new study’s conclusions are “limited” by the small dataset.
Koenraad Van Doorslaer, interim co-chair of the immunobiology department at the University of Arizona who was not involved in the study, told Live Science in an email he “largely” agreed with the paper’s conclusions, noting the authors “rigorously demonstrated” that both individuals were likely infected with HPV16.
“I am genuinely excited about the implications of this study because it supports some critical assumptions about the history of this family of important viruses,” Van Doorslaer said.
However, Van Doorslaer said the proposal of the study authors that their findings present a challenge to the idea that HPV16A first entered our species due to Neanderthal interbreeding “may be overstated” in light of the data presented. In part, because Ust’-Ishim was previously shown to have Neanderthal DNA in his genome, “suggesting that the interbreeding pre-dates Ust’-Ishim’s life,” Van Doorslaer said. “So since this sample both has Neanderthal DNA and HPV16 DNA, it does not prove that HPV16 does not come from Neanderthals.”
