Human Papilloma Virus Linked to Throat Cancer

BALTIMORE, May 9 -- Human papilloma virus (HPV), known to cause a range of anogenital cancers, has also been associated with a dramatically increased risk of some throat cancers, according to researchers here.

In a case-control study of newly diagnosed oropharyngeal squamous-cell carcinoma, infection with virus type 16 was associated with nearly a 15-fold increase in risk, according to Maura Gillison, M.D., Ph.D., of Johns Hopkins.

And seropositivity for the type 16 virus -- regarded as a measure of lifetime exposure to the virus -- was associated with a 32-fold increase in risk, Dr. Gillison and colleagues reported in the May 10 issue of the New England Journal of Medicine.

Oral sex is probably the main way the virus is transmitted, the researchers said, although mouth-to-mouth transmission -- as in kissing -- can't be ruled out.

"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," said Gypsyamber D'Souza, Ph.D., of the Johns Hopkins Bloomberg School of Public Health, a study co-author.

The HPV link has been suspected for some time, Dr. Gillison and colleagues said, mainly because molecular evidence shows that 26% of all squamous-cell carcinomas of the head and neck have signs of oncogenic HPV and the proportion is higher for oropharyngeal cancer.

To attack the epidemiological side of the issue, the researchers enrolled 100 patients with oropharyngeal squamous-cell carcinoma and matched each of them with two healthy controls of the same sex and within five years of age.

The researchers sampled participants' blood and saliva, collected information -- using an anonymous questionnaire -- on sex practices, tobacco and alcohol exposure, family history, and oral hygiene.

The study found that genetic material from HPV 16 was present in 72% of the tumors. Also:

• Oropharyngeal cancer was associated with active oral HPV-16 infection, with an odds ratio of 14.6 and a 95% confidence interval from 6.3 to 36.6.
• Cancer was also associated with oral infection with any of 37 types of HPV, with an odds ratio of 12.3 and a 95% confidence interval from 5.4 to 26.4.
• Cancer was associated with seropositivity for the HPV-16 L1 capsid protein, with an odds ratio of 32.2 and 95% confidence interval from 14.6 to 71.3.

The analysis also found that a high lifetime number of vaginal-sex partners -- defined as 26 or more -- was associated with cancer. The odds ratio was 3.1, with a 95% confidence interval from 1.5 to 6.5.

The same was true for a high lifetime number of oral-sex partners (defined as six or more), where the odds ratio was 3.4 with a 95% confidence interval from 1.3 to 8.8.

The researchers found that the link became stronger as the numbers of vaginal-sex and oral-sex partners increased -- the P-values for the trends were 0.002 and 0.009, respectively.

Interestingly, although tobacco and alcohol use are traditionally considered the key risk factors for oropharyngeal squamous-cell carcinoma, the study showed no added risk for tobacco and alcohol users.

"It's the virus that drives the cancer," Dr. Gillison said. "Since HPV has already disrupted the cell enough to steer its change to cancer, then tobacco and alcohol use may have no further impact."

The study raises some important clinical questions "now that the association between some cases of oropharyngeal cancer and HPV infection appears to be firmly established," said Stina Syrjnen, D.D.S., Ph.D., of the University of Turku in Finland, in an accompanying editorial.

Those questions, Dr. Syrjnen said, include:

• If there's a need to screen high-risk groups, such as smokers and drinkers, for persistent oral or oropharyngeal HPV infection.
• Whether HPV-associated cancers should be treated in the same way as those that are HPV-negative, but linked to heavy smoking and drinking.
• Whether some oral, oropharyngeal, and laryngeal cancers might be prevented by HPV vaccination.

Dr. Syrjnen reports receiving consulting fees from Merck.