HPV-associated head and neck cancer: a virus-related cancer epidemic

Abstract

Summary A rise in the annual incidence of oropharynx squamous cell cancer, specifically the lingual and palatine tonsils, in white men under the age of 50, non-smokers and non-alcoholics, has been observed over the past decade. This entity is associated with human papilloma virus-16 infection and the risk factors include an increased number of oral and vaginal sex partners at a younger age. The biology of HPV-related oropharynx cancer is distinct with p53 degradation, Rb pathway inactivation, and p16 upregulation. This is in contrast to tobacco related oropharynx cancer which is characterized by p53 mutation and downregulation of p16. The optimal method to detect virus in tumor is controversial and both in situ hybridization and PCR are commonly used; p16 immunohistochemistry may serve as a potential surrogate marker. HPV-related oropharynx cancer appears to be more responsive to chemotherapy and radiation than HPV negative orpharynx cancer. HPV-16 is a prognostic marker for improved overall survival and disease-free survival but has not yet been shown to be a predictive marker. Investigators continue to explore unanswered questions regarding the natural history of oral HPV infection, why the increase dominates in men, the potential of HPV vaccines for primary prevention, developing a commercially available accurate method to detect the virus in tumor, and treatment strategies that reduce toxicity without compromising survival. The goal of this review is to highlight our current understanding of the epidemiology, biology, detection, as well as current management and unresolved issues of HPV-related oropharyngeal HNSCC.