Tobacco users have a higher prevalence of infection with oral human papillomavirus type 16 (HPV16), according to a new study in the Journal of the American Medical Association (October 8, 2014, Vol. 312:14, pp. 1465-1467).
While the overall incidence of head and neck cancer is decreasing in the U.S., recognized cases of oropharyngeal squamous cell carcinoma (OPSCC) are increasing. About 70% of an estimated 30,000 oropharyngeal cancer cases in the U.S. annually are attributed to HPV, the most common sexually transmitted infection in the U.S. Studies show that most patients with OPSCC are HPV-positive, especially for HPV types 16 and 18.
An association between the self-reported number of cigarettes currently smoked per day and oral HPV prevalence has been observed, according to the JAMA study.
In the study, Carole Fakhry, MD, from the Johns Hopkins University School of Medicine, and colleagues investigated associations between objective biomarkers reflective of all current tobacco exposures (environmental, smoking, and use of smokeless tobacco) and oral HPV16 prevalence. The researchers used data from the National Health and Nutrition Examination Survey (NHANES).
Mobile examination center participants ages 14 to 69 years were eligible for oral HPV DNA testing. Exfoliated oral cells were collected using a 30-sec oral rinse and gargle and tested for HPV16.
Computer-assisted self-interviews were used to determine self-reported tobacco use and sexual behaviors. SelfÂreported tobacco use for the past five days included any nicotineÂcontaining product. Biomarkers of recent tobacco use included serum cotinine, a major nicotine metabolite, and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobaccoÂspecific, carcinogenic metabolite.
Of more than 20,000 participants interviewed, the analysis was restricted to participants aged 18 to 59 years (n = 8527) with data on oral HPV16 and recent tobacco use (n = 6,887).
Results
Of the 6,887 participants, 2,012 (28.6%) were current tobacco users and 63 (1.0%) had oral HPV16 detected. Current tobacco users were more likely than nonusers to be young men, to be less educated, and to have a greater number of lifetime oral sexual partners.
Self-reported and biological measures of tobacco exposure as well as oral sexual behavior were significantly associated with prevalent oral HPV16 infection, the researchers found. Oral HPV16 prevalence was greater in current tobacco users (2.0%) than former tobacco users or those who never used tobacco (0.6%). The average cotinine and NNAL levels were higher in participants with oral HPV16 infection than those without infection.
Each log increase in cotinine, approximating three cigarettes per day, was independently associated with oral HPV16 prevalence. In addition, each log increase in NNAL, approximating four cigarettes per day, was also independently associated with oral HPV16 prevalence.
"Although adjusted for sexual behavior, we cannot entirely exclude the possibility that tobacco use is a marker for risky behavior," the group observed.
The large, cross-sectional, population-based study demonstrated statistically significant dose-response relationships between behavioral and objective biomarkers of current tobacco use and oral HPV16 infection, the researchers concluded.
"Tobacco use is an established co-factor for the development of cervical cancer, for which HPV infection is a necessary cause," they wrote. "Tobacco use has local and systemic immunosuppressive effects; however, the specific biological mechanisms underlying our observed associations are unknown."
"Tobacco use may alter determinants of oral HPV16 prevalence, such as incidence, persistence, or reactivation of infection," the researchers concluded. "These findings highlight the need to evaluate the role of tobacco in the natural history of oral HPV16 infection and progression to malignancy."
