Public Health Challenge

There are approximately 400,000 cases of head and neck cancer diagnosed world-wide each year. Head and neck cancer has a high mortality rate which has not improved in the past decade. Each year in the United Stated there are about 30,000 new head and neck cancer cases (~4,650 oropharyngeal cases) making it the sixth most common malignancy. HPV (Human Papillomavirus) is a small circular DNA virus only known to infect humans. The virus specifically infects basal cells in the squamous epithelium. There are over 100 types of HPV that are distinguished based on variations in their genetic sequence, which are classified broadly into those types of HPV that are known to cause cancer (high risk) and those with no known oncogenic potential (low risk). HPV is a necessary (but not sufficient) cause for all cervical cancers, and is known to cause a subset of vaginal, penile, anal, and head and neck cancers.

Research Findings

HPV DNA is found in tumor of 10-20% of all head and neck cancers, and 40-75% of oropharyngeal cancers. Oral HPV DNA prevalence is significantly increased in individuals with more oral sexual partners. Oral HPV prevalence also increased with increases with age, is more common in men, current tobacco users and in HIV-infected individuals with low CD4 levels. Patient characteristics and survival differ between HPV-positive and HPV-negative head and neck cancer patients. HPV-positive head and neck cases are more likely than HPV negative patients to have cancers in the palatine and lingual tonsils, to be poorly differentiated (basaloid), nonsmokers, nondrinkers, younger age, White, and higher socio-economic status. Risk factors for HPV-positive and HPV-negative cancers also differ. Tobacco use, alcohol use and poor oral hygiene are important risk factors for HPV-negative head and neck cancer but are not associated with risk of HPV-positive cancer. In contrast, number of oral sex partners and marijuana use are associated with odds of HPV-positive but not HPV-negative head and neck cancer. This suggests that head and neck cancer is a heterogeneous group of malignancies i.e. HPV-positive and HPV-negative head and neck cancers are two distinct cancers.

Possible Directions

Dr. D’Souza’s research has helped to establish that HPV in an etiologic cause of a subset of oropharyngeal cancers. Now it is important to understand the transmission and natural history of oral HPV infection and differences in HPV-positive oral cancers. Next steps towards these goals include: i) partner studies to establish which sexual behaviors are associated with the transmission of HPV to the oral cavity; ii) longitudinal studies to explore median time to clearance of oral HPV infection, factors which affect clearance, and risk of progression; and iii) as HPV positive and HPV negative cancers may respond to therapies differently, whether HPV status should be considered in the future in designing optimal treatment strategies needs to be evaluated.

Future Research Opportunities

HPV vaccines Gardasil (by Merck) and Cervarix (by GSK) have been shown to be effective in preventing new cervical HPV infections and therefore preventing cervical cancer. It is unknown how these vaccines effect oral HPV infection, but as more than 90% of HPV-positive head and neck cancers are caused by HPV16 (one of the 4 HPV types in the Gardasil vaccine) there is reason to be optimistic vaccination may be effective in preventing HPV-associated oral cancers as well.