Over Two Thirds of Americans Harbor HPV, Genomics Study Reveals

Pam Harrison

May 22, 2014

More than two thirds of healthy US residents harbor at least 1 type of human papillomavirus (HPV), most of which are undetectable by widely used commercial screening kits, a large genetic analysis shows. However, the relevance of this is at present unclear, commented an expert not connected with the study.

The study identified 109 different HPV types in tissue samples taken from 103 men and women whose tissue DNA was made available through the National Institutes of Health (NIH) Human Microbiome Project.

Only 4 individuals carried either HPV 16 or 18, considered to be among the most oncogenic HPV types and associated in particular with cervical cancer.

"There are more than 170 HPV types, so it's a very heterogeneous virus, and current methods only detect about 20 to 30 of them," senior investigator Zhiheng Pei, MD, PhD, associate professor of pathology, New York University School of Medicine, in New York City, told Medscape Medical News.

"[Because] non-risk or low-risk HPV types have been very understudied, we would like to see if these non-cancer-causing HPV types play a role in cancers other than cervical cancer or, conversely, if HPV infection is in fact beneficial in an asymptomatic population," Dr. Pei commented.

The study was presented at the annual meeting of the American Society for Microbiology in Boston, Massachusetts.

Shotgun Sequencing

For the study, researchers decoded DNA assembled by a technique called shotgun sequencing.

In this method, researchers fragment long DNA strands into short fragments and then randomly sequence each small fragment, as Dr. Pei explained.

In all, DNA from 748 tissue swabs was analyzed. Tissue was taken from multiple organ sites, including the skin, vagina, mouth, and gut. Tissue was collected in 2009 at a time when HPV vaccination was not popular, as Dr. Pei observed.

All human DNA was removed, and HPV DNA was matched to an HPV reference genomic database.

This allowed researchers to see the entire community of HPV types in a healthy segment of the population.

The highest prevalence of HPV infection was found on the skin, at 61.3%. This was followed by the vagina, with a prevalence of 41.5%; the mouth, at 30%; and the gut, at 17.3%.

Multiple HPV types were also detected in 48.1% of all HPV-positive samples.

"Our study offers initial and broad evidence of a seemingly 'normal' HPV viral biome in people that does not necessarily cause disease and that could very well mimic the highly varied bacterial environment in the body, or microbiome, which is key to maintaining good health," Dr. Pei said in a press release.

As researchers suggest, the overwhelming presence of so many HPV viral strains in a normal, healthy viral biome may be an indication that certain viral strains could be keeping each other in check so that other strains do not spread out of control.

On the other hand, more and more studies are identifying HPV-related cancers in body sites other than the uterine cervix, as Dr. Pei noted. In particular, there has been an increase in HPV- related oropharyngeal cancers in recent years.

It therefore could be that the so-called low-risk or nononcogenic HPV types could actually be implicated in cancers at these different sites, including oral cancer, oropharyngeal cancer, and skin cancer.

"Right now, we certainly don't know what this high prevalence of HPV infection means in a healthy population, and more investigations are needed to understand the impact of asymptomatic HPV infection on human health," Dr. Pei told Medscape Medical News.

"So we need to see the complete picture of HPV infection, and eventually, we will know what this high HPV prevalence means, and we can then perhaps suggest some additional HPV types that should be included in the clinical detection kit to broaden HPV detection."

Relevance to Human Disease Is Unclear

Asked to comment on the study, Maura Gillison, MD, PhD, professor and Jeg Coughlin chair of cancer research at the Ohio State University, in Columbus, Ohio, told Medscape Medical News that it is difficult to tell to what extent the sample of only 103 individuals represents the US population as a whole.

"Based on the older methods capable of detecting 37 HPV types, the CDC [US Centers for Disease Control and Prevention] estimated that ~42.5% of US women have a cervical HPV infection at any point in time," she noted, adding that it is "perhaps surprising" that with shotgun sequencing, only 42% of women in the Microbiome Project sample had a vaginal infection.

"I would think the estimates would be more dramatically different from one another," Dr. Gillison added.

She concurred with investigators that although the study is interesting, "at this time, it's of unclear relevance to human disease."

The study was funded by the NIH Roadmap Initiative's Human Microbiome Project, the National Cancer Institute, the Office of Research and Development, the Veterans Health Administration, and the US Department of Veterans Affairs. Dr. Pei and Dr. Gillison have disclosed no relevant financial relationships.

The 114th General Meeting of the American Society for Microbiology. Poster presentation 2357. Presented May 20, 2014.


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