Advances in Tumor Virology

The evidence is that infection with high-risk human papillomavirus (HRHPV), particularly HPV 16, is the cause of the increase in incidence over the past 2–3 decades, in economically developed countries, of oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinomas (HNSCC). HRHPV DNA sequences are detected in HNSCC with tonsil and base of tongue, the sites with the highest prevalence of HPV+ve carcinomas. HRHPV E6/E7 mRNA oncogene expression and p16INK4A overexpression (a marker of HRHPVE7 overexpression) are detected in 50–80% of OPSCC depending on geographical locale. Evidence from in vitro studies with oral keratinocyte cell lines and E6/E7 transgenic mice shows that E6/E7 oncogene expression is required for initiation and maintenance of the malignant phenotype. Case–control and cohort studies show that risk for OPSCC is associated with HPV exposure prior to cancer diagnosis. The experimental and epidemiological data provide robust evidence for a causal role in OPSCC, but the evidence for association of HPV with other HNSCC such as oral cavity or larynx is weak.