A new study of oropharyngeal cancer suggests that dramatic increases in U.S. incidence of the cancer and survival since 1984 can be attributed to infection with the human papillomavirus (HPV). Using samples collected from registries in three states, researchers showed that the proportion of oropharyngeal cancers - particularly among men - that tested positive for HPV increased significantly over time, from slightly more than 16 percent of such cancers diagnosed during the 1980s to more than 70 percent diagnosed during the 2000s. Based on these trends the researchers predict that incidence of oropharyngeal cancers will exceed that of cervical cancer in the next decade.
Previous studies have shown that oropharyngeal cancers can be divided into two separate diseases with distinct causes: HPV-negative cancers, which are associated with tobacco and alcohol use; and HPV-positive cancers, which are linked to certain types of HPV, a sexually transmitted virus. Patients with HPV-positive oropharyngeal cancer also tend to be younger than those who are HPV-negative. Clinically, patients with HPV-positive cancer tend to have better survival compared to those with HPV-negative disease.
"We used to think of oropharyngeal cancer as one cancer, and now we know the disease is comprised of two biologically and epidemiologically distinct cancers. This new understanding will increasingly enable us to improve and better personalize care for patients with each form of the disease," said senior author Maura Gillison, MD, PhD, professor of medicine and Jeg Coughlin Chair of Cancer Research at The Ohio State University Comprehensive Cancer Center in Columbus.
Gillison and her team previously showed that incidence and survival rates for oropharyngeal cancers significantly increased in the U.S. from 1973 to 2004, whereas the incidence rates for other head and neck cancers, such as oral cavity cancers, declined during that period.
To determine the role of HPV infection in these trends, researchers tested 271 archived oropharynx cancer tissue samples (from 5,755 patients) for HPV infection collected between 1984 and 2004 at three population-based cancer registries located in Hawaii, Iowa and Los Angeles in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Residual Tissue Repositories Program. Using a variety of molecular assays, the investigators showed that the proportion of oropharynx cancers that were HPV-positive dramatically increased over time, from 16.3 percent for cancers diagnosed during the 1980s (1984 to 1989) to 72.7 percent for cancers diagnosed during the 2000s (2000 to 2004).
On a population level, they discovered that over just 16 years (1988 to 2004), the incidence of HPV-positive cancers rose from 0.8 per 100,000 to 2.6 per 100,000 - an increase of 225 percent. HPV-negative oropharyngeal cancers declined by 50 percent during that same time, likely due to declines in smoking and tobacco use.
According to Gillison, if current trends continue, the study suggests HPV-related oropharyngeal will become the major form of head and neck cancer and the leading HPV-associated cancer in the U.S., surpassing cervical cancer, by 2020.
"These increases may reflect increases in sexual behavior, including increases in oral sex," Gillison said. She noted that approximately 90 percent to 95 percent of HPV-positive oropharynx cancers were caused by one HPV type - HPV16, which is targeted by currently available vaccines for cervical cancer prevention. "But with HPV vaccines, we have a great opportunity to potentially prevent oropharynx cancers in future generations - including in boys and men - but studies need to be done to evaluate the efficacy of HPV vaccines in preventing oral HPV infections."
Further research is needed to address several other key questions, said first author Anil Chaturvedi, PhD, investigator in the Division of Epidemiology and Genetics at the National Cancer Institute in Rockville, MD. "Prospective studies are needed to investigate the natural history of oral HPV infection because little is currently known about its incidence and persistence, any modifiable risk factors involved in its persistence and opportunities for screening."
The oropharynx is the middle part of the throat behind the mouth, and includes the base of the tongue, the soft palate, the side and back walls of the throat and the tonsils. Oropharyngeal cancer is the second virus-related head and neck cancer known, with the other being nasopharyngeal cancer (Epstein-Barr virus). Gillison said that while clinically both groups of oropharyngeal cancers seem the same, histopathologically, they appear different, and the response to treatment is different. Clinical trials groups, she said, are designing trials stratified according to HPV status. The authors noted that patients with HPV-positive disease generally have a better prognosis than those with HPV-negative disease, and that radiation - in addition to chemotherapy - has a particularly strong impact on long-term outcomes. By contrast, for HPV-negative patients, there have been few treatment advances in 20 years that have led to improved survival.
"This is a significant study because it clarifies the growing role of HPV as a causative agent in head and neck cancer. The findings could have particular relevance for HPV vaccine administration policy and recommendations for those at risk for HPV-related cancers. We now have stronger evidence to tie behaviors to the incidence of different variations on this one cancer type. What is interesting is that these findings about the incidence of oral cancer are in line with the simultaneous changes in sexual behavior patterns and the decline in smoking. We are encouraged by what the availability of HPV vaccines may be able to do to prevent these cancers now that we have a clearer understanding of causation, but we also have more work to do for those cancers unrelated to HPV."
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