Researchers at the Johns Hopkins Kimmel Cancer Center have conclusive evidence that human papillomavirus (HPV) causes some throat cancers in both men and women. Reporting in the May 10 issue of the New England Journal of Medicine, the researchers found that oral HPV infection is the strongest risk factor for the disease, regardless of tobacco and alcohol use, and having multiple oral sex partners tops the list of sex practices that boost risk for the HPV-linked cancer.
Study author and cancer virus expert Maura Gillison, M.D., Ph.D., first reported the connection between HPV and specific throat cancers in 2000, supporting previous work by other investigators. "We believed the links were strong, but needed to understand which behaviors put people at higher risk," says Gillison.
Gillison added that "people should be reassured that oropharyngeal cancer is relatively uncommon, and the overwhelming majority of people with an oral HPV infection probably will not get throat cancer," says Gillison. Consistent condom use may reduce risk.
In Gillison's study of 100 men and women newly diagnosed with oropharyngeal cancer (located in the tonsils, back of the tongue, and throat), those who had evidence of prior HPV infection were 32 times more likely to develop the cancer. This was much higher than the rate increase of threefold for smokers and 2 ½ -fold for drinkers. Study participants who reported having more than six oral sex partners in their lifetime were 8.6 times more likely to develop the HPV-linked cancer. In a surprising twist, Gillison says their data show no added risk for HPV carriers who smoke and drink alcohol. "It's the virus that drives the cancer," explains Gillison, an assistant professor of oncology and epidemiology at Johns Hopkins. "Since HPV has already disrupted the cell enough to steer its change to cancer, then tobacco and alcohol use may have no further impact."
"It is important for health care providers to know that people without the traditional risk factors of tobacco and alcohol use can nevertheless be at risk for oropharyngeal cancer," says Gypsyamber D'Souza, Ph.D., a co-author and assistant scientist at the Johns Hopkins Bloomberg School of Public Health.
Oral sex, including both fellatio and cunnilingus, is the main mode of transit for oral HPV infection, the investigators say, although mouth-to-mouth transmission remains possible and was not ruled out by the current study.
HPVs also can be transmitted by skin contact and are found in the mucus of the genital tract, and in saliva, urine, and semen. Both men and women contract the ubiquitous virus in equal numbers, which is believed to have infected a large proportion of people worldwide at some point in their lives. Most HPV infections clear with little or no symptoms, but a small percentage of men and women who acquire cancer-causing or "high-risk" strains, such as HPV 16, may develop a cancer. HPV-linked cancers currently include oral, anal, cervical, vaginal, penile, and vulvar cancers.
Gillison said a new FDA-approved vaccine, known by its tradename Gardasil, can prevent genital HPV infection in girls and young women, but has not yet been shown to prevent infection in boys and men. The vaccine's ability to prevent oral HPV infection and oral cancers, which are more common in men, also is not known. Although HPV detection is now added to the Pap smear for cervical cancer screening, there are no screening methods for oral cancers besides visual inspection during annual dental visits. But Gillison says that it's still too early to recommend including HPV detection in oral cancer screening.
Along with an anonymous survey, Gillison and her colleagues sampled participants' blood and saliva. Eighty-six of the 100 patients were male and 14 were female. They collected information on sex practices and other risk factors for the disease, including tobacco and alcohol exposure, family history, and poor oral hygiene. Answers were compared with those of 200 control subjects with benign conditions.
HPV 16 was present in the tumors of 72 percent of oropharyngeal cancer patients enrolled in the study. People with detectable antibodies in their bloodstream to molecules made by HPV were 58 times more likely to have these oral cancers, a figure that dwarfs the connection between high cholesterol and heart attacks. The researchers also were able to find higher risk in patients with traces of HPV in oral rinses, a first step to developing a "swish-and-spit" screening method for at-risk individuals.
HPV-linked oral cancers have been on the rise since at least 1973, and Gillison expects the trend to continue to a point when HPV-associated cancers will far outpace those caused by tobacco and alcohol use. They currently account for 60 percent of oropharyngeal cancers and about a third of all oral cavity and pharynx cancers in the United States, totaling more than 11,000 individuals*.
For those who already have HPV-linked oropharyngeal cancer, there is some good news. Gillison's previous studies, along with others, showed that these patients have a survival advantage with most living well past the five-year mark.
"We're getting more intensive in our cancer treatments and seeing a survival benefit, but it may not be the therapy alone that's causing this. It could also be the increasing percentage of treatment-friendly HPV cancers," suggests Gillison. Researchers would still need to assess how to safely ratchet back therapy, which causes severe swallowing, breathing and talking problems.
As for an oral rinse screening test, its feasibility still remains unproven. For this study, Gillison and her colleagues spent two years refining methods to detect HPV in oral samples. She also is working with manufacturers of the new FDA-approved vaccine for HPV to determine its potential in curbing oral cancers.
Funding for the research was provided by the Damon Runyon Cancer Research Foundation, the Johns Hopkins Cigarette Restitution Fund Program and the National Institutes of Health.
Co-authors include Gypsyamber D'Souza, Ph.D., Raphael Viscidi, M.D., Carole Fakhry, M.D., Wayne M. Koch, M.D., and William H. Westra, M.D., from Johns Hopkins; Aimee R. Kreimer, Ph.D., from the National Cancer Institute; and Michael Pawlita, M.D., at the German Cancer Research Center in Germany.
* American Cancer Society, Facts and Figures 2007.
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