CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.
If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.
The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.
Consequently, the overall incidence of oropharyngeal cancers increased 28%.
Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.
Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.
Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).
The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.
Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.
"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."
The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.
Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.
It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.
Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.
"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."
In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.