Tonsillar cancer (TC) is the most common oropharyngeal cancer and tumours are mainly squamous cell carcinomas. Traditionally, risk factors for the development of TC include the use of alcohol and/or tobacco, however a significant proportion of new cases develop in young patients without these risk factors. Recent investigation suggests that human papilloma virus (HPV) may serve as an etiology in such cases and represent a unique risk factor in a sub-set of patients. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression, and an inverse association with EGFR amplification. HPV-16 integration status was strongly associated with c-myc amplification and HIF-1a overexpression. HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase.
