Oropharyngeal cancer: clinical implications of the HPV connection

Abstract

In addition to cervical cancer, the most widely established human papillomavirus (HPV)-associated malignancy, HPV has been implicated in the development of a subset of oropharyngeal cancers [1, 2]. Several lines of evidence support the causative role of HPV in oropharyngeal squamous cell carcinomas (OSCC). According to a workshop hosted by The Cancer Etiology Branch of the National Cancer Institute entitled ‘Validation of a Causal Relationship: Criteria to Establish Etiology’, four types of evidence are necessary to establish a causal relationship in cancer: epidemiological, molecular pathological, experimental, and evidence derived from animal studies [3]. There is strong epidemiological and molecular pathology evidence indicating that HPV16 is associated with a subset of OSCC [4,–7]. Rampias et al. [8], by showing that E6 and E7 oncogene repression restores p53 and retinoblastoma tumor suppressor pathways and induces apoptosis in HPV16+ oropharyngeal cancer cell lines, provided experimental evidence that HPV16 is causally associated with a subset of OSCC. In addition, it has become clear that HPV-positive OSCC is defined by unique patient demographics and disease characteristics. HPV-positive patients tend to be younger with less exposure to tobacco and alcohol. The cancers are increasing in incidence; almost exclusively confined to the palatine tonsil and base-of-tongue; tend to present with lower T-stage and higher N-stage; and have been strongly epidemiologically linked with sexual activity, especially oral sex.