Human Papillomavirus and head and neck cancer: Epidemiology and molecular biology

BACKGROUND: Human papillomaviruses (HPV) are known to cause cancers of the cervix and other anogenital tract sites. Molecular biology has provided some evidence as to the specific mechanisms involved in the HPV-related carcinogenesis. Epidemiologic and molecular biology studies have also suggested that HPV infection may be associated with cancers of the head and neck. METHODS: This review summarizes the biology of HPV and its potential etiologic role in head and neck cancer. Published reports were used to determine the prevalence of HPV in benign, precancerous, and neoplastic lesions of the oral cavity, pharynx, and larynx. The prevalence was also examined by head and neck site, HPV type, and method of HPV detection. In addition, the occurrence of HPV in normal head and neck tissue, epidemiologic factors related to HPV infection, and clinical implications are discussed. RESULTS: Overall, the frequency of HPV in benign and precancerous lesions ranged from 18.5% to 35.9%, depending upon the detection methodology. Based upon the most sensitive method of detection, polymerase chain reaction (PCR), the overall prevalence of HPV in head and neck tumors was 34.5% (416 of 1205 tumors). The majority of HPV-positive tumors contained the "high risk" HPV types 16 (40.0%) and 18 (11.9%). Among head and neck sites, HPV was most often detected in tumors of the oral cavity (59%), followed by the pharynx (43%), and larynx (33%). The frequency of HPV positivity in oral samples from healthy individuals ranged from 1% to 60%. A limited number of descriptive and analytic epidemiologic studies have indicated that age (<60 years) and sex (male) were associated with the presence of HPV in the tumor, whereas tobacco and alcohol use were not. The relationship between HPV and survival is unclear, with few comprehensive studies currently available. CONCLUSIONS: The prevalence of HPV, particularly the high-risk types, suggests a potential etiologic role for the virus in head and neck cancer. Molecular biology has provided important data on the interaction of the HPV oncoproteins with genes important in cell cycle control. Nonetheless, more basic research is needed to describe the physical state of the virus in a variety of cell types and the interaction with other genes. In addition, epidemiologic research is required to further understand the association between HPV and demographic and other risk factors as well as possible routes of transmission. Finally, much work is warranted to provide a definitive assessment of the prognostic significance of HPV in head and neck cancer.