Different high-risk HPV infections don’t spur cancers at the same rate

A study mapped the frequency at which different high-risk human papillomavirus (HPV) strains progress to cervical cancer and linked some strains to distinct genetic signatures, which could help scientists better understand these infections and open the door to targeted treatment approaches. 

The study published in Tumour Virus Research examined more than 700 cancer-free, precancer, early-stage cancer, and invasive cancer biopsy samples obtained from women in Guatemala who underwent screening or treatment in a hospital setting.  

Looking at a spectrum of precancer and cancer stages allowed the researchers to analyze trends between HPV strains and cancer progression.  

HPV is a common sexually transmitted infection. Most cases eventually get cleared by the immune system. However, women who have a lasting infection with any one of 15 high-risk strains can develop cervical cancer. These cancers are preventable and can be treated but still cause over 300,000 deaths worldwide each year, mainly in resource-limited areas, underscoring the need to better understand, prevent, and treat the disease. 

The study represents a recent effort to do that—and to address health disparities in low- and middle-income populations, both in the U.S. and globally. 

“The biology of cervical cancer is more or less the same around the world,” said Michael Dean, Ph.D., one of the study’s senior authors and a senior investigator in the Laboratory of Translational Genomics at the National Cancer Institute. “The data that we generate in one population can be applied to patients here or anywhere around the world.” 

The study emerged from a longstanding partnership between Dean’s laboratory at NCI and the Hospital General San Juan de Dios in Guatemala. The Cancer Genomics Research Laboratory at Frederick National Laboratory for Cancer Research, another longstanding partner with Dean’s laboratory, characterized different HPV types as part of the study. 

One finding stood out among the others, said Emma Robinson, the study’s lead author and a biostatistician working with the Laboratory of Translational Genomics, who also works part-time at Frederick National Laboratory. Most samples bearing an HPV31 infection, a high-risk strain, were precancerous rather than early-stage or invasive cancer. It was the opposite of what the team expected, given that some high-risk strains, such as HPV16 and HPV18, are abundant in cervical cancer.  

“In Guatemalan patients, at least, it appears that HPV31, although it’s classified as a high-risk HPV type, is more likely to stop in the precancer stage and not progress to stage-one cancer or invasive cancer—or at least progress much more slowly," Robinson said. "So, that has interesting clinical implications." 

She added that analyses in other populations would clarify whether HPV31 infections behave the same globally. 

The team also analyzed the genetic signatures of HPV31 and the high-risk strain that’s most implicated in cervical cancers, HPV16. They pinpointed a bevy of genetic differences between the two, many of which helped reveal why the two infections have such different outcomes. 

For instance, two genes associated with cell division, CCNE1 and MELTF, are more common in HPV16 precancers than HPV31 precancers. With rampant, unchecked cell division being a hallmark of cancer progression and growth, this suggests that these genes contribute to the comparatively rapid progression to cancer in HPV16 infections. 

Separately, the team performed a second analysis that used The Cancer Genome Atlas to trace correlations between the level of certain genes and disease prognosis across cancer stages. Several genes were linked to an improved chance of surviving the disease, and one, ULBP2, was linked with an increased chance of death. 

This information creates an opportunity for others to develop new treatments or identify existing treatments that can exploit the HPV-related genetic signatures to attack the tumors. Robinson said scientists can try to find drugs that could target those overall pathways in a majority of people.

The team acknowledges that similar studies in samples from other populations would make the findings more generalizable to more women. Their current study, however, is meant to foster that pursuit—another step closer to better understanding and treating cervical cancer for all.