Researchers at the Johns Hopkins Kimmel Cancer Center have teased out two distinct sets of risk factors for head and neck cancers, suggesting that there are two completely different kinds of the disease.
In the Johns Hopkins study, head and neck tumors caused by the human papillomavirus (HPV), a common sexually transmitted virus, were most often linked to certain sexual behaviors and marijuana use, rather than tobacco and alcohol. The Johns Hopkins scientists also found that people with the viral-linked cancer were younger, more likely to be white, married, college-educated and have an annual income of $50,000 or higher. By contrast, those not caused by HPV, were associated with tobacco smoking, alcohol use and poor oral hygiene, which are the behaviors most often linked to head and neck cancer.
"Our results indicate that HPV-positive and HPV-negative head and neck cancers have different risk-factor profiles and should be considered two distinct diseases," says Maura L. Gillison, M.D., Ph.D., an associate professor of oncology and epidemiology at Hopkins. "They just happen to occur in the same place."
The findings are to be published in the March 12 issue of the Journal of the National Cancer Institute.
Gillison and her colleagues first reported in 2000 that HPV infection is associated with the development of some head and neck cancers, particularly in the upper throat and back of the tongue (oropharynx), where it has been observed in up to 72 percent of patients. In related work, Gillison and colleagues recently reported that HPV-linked cancer has nearly doubled in incidence over the past 30 years in the United States. They also found that head and neck cancer patients with HPV-positive tumors tend to survive longer and are more responsive to treatment, compared with patients with HPV-negative tumors. That research was published online Feb. 12 also in the Journal of the National Cancer Institute. According to Gillison, the American Joint Committee on Cancer is now considering incorporating HPV status in its guidelines for determining clinical stages of head and neck cancer.
For the current study, Gillison and her team studied 240 patients diagnosed with head and neck squamous cell carcinomas at the Johns Hopkins Hospital between 2000 and 2006, and determined whether their tumors were positive or negative for HPV. They formed a control group by matching up to two people without cancer to each patient by similar age and sex. All study participants completed a computerized interview that asked questions about their risk factors.
Overall, the researchers detected HPV16 in 92 cancer patients. They found that HPV-positive cancers were associated with several measures of sexual behavior and exposure to marijuana but not with tobacco or alcohol use, or with poor oral hygiene. These associations became stronger with increasing numbers of oral sex partners, and with longer or more intense use of marijuana. In fact, among nonsmokers of tobacco, participants who smoked marijuana for at least five years were 11 times more likely to develop HPV-positive cancers.
Gillison says that her study is one of the first to connect marijuana use with the development of HPV-linked head and neck cancers. "It's possible that other behaviors linked with marijuana use could be the real culprit, and our results will need to be confirmed," she says. Some reports show that chemicals in marijuana called cannabinoids could affect the immune system's ability to clear a viral infection, according to Gillison.
Sexual behaviors associated with HPV-positive cancers included increasing numbers of lifetime vaginal or oral sex partners, participating in casual sex at least once, infrequent use of barriers during vaginal or oral sex, and having had at least one sexually transmitted disease. HPV-negative cancers were found to be associated with tobacco or alcohol use and with poor oral hygiene but not with any measure of sexual behavior or marijuana use. Poor oral hygiene, tobacco and alcohol use are well-known risk factors for non-HPV related head and neck cancer. Those who had heavily used tobacco and alcohol were nearly five times more likely to develop HPV-negative head and neck cancers. Participants who brushed their teeth less than once a day were four times more likely to develop HPV-negative tumors.
Head and neck cancers occur in more than 35,000 Americans each year, and the Johns Hopkins investigators believe that the rise in the HPV variety could be due to changing sexual behaviors.
This research was supported by the Damon Runyon Cancer Research Foundation, the State of Maryland Cigarette Restitution Fund, and the National Institute of Dental and Craniofacial Research.
Coauthors were Gypsyamber D'Souza, Ph.D.; William Westra, M.D.; Elizabeth Sugar, Ph.D.; Weihong Xiao, M.D.; Shahnaz Begum, M.D., Ph.D.; and Raphael Viscidi, M.D.
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