Current data have now attributed a viral etiology and causality of Human papillomavirus (HPV). Epidemiological analysis of the last decade demonstrates a rapid increase of HPV-associated
HNSCC. Genomic detection of HPV
DNA in the nuclei of certain oro-
pharyngeal cancer cells gives strong evidence of a viral etiology in
HNSCC. Non-smokers, non-drinkers, and a sexual debut at a younger age and other sexual risk factors have an increased risk of HPV-positive
oropharyngeal cancer. Sexual transmission is considered to play a causal role. In contrast to HPV-negative
HNSCC most studies reveal a favorable prognosis for HPV-positive
tumors. There is evidence of alterations in the p53 pathway through expression of E6 oncogene with subsequent induction of
tumor cell proliferation. Synergies between viral oncogenes and other
carcinogens are hypothesized. HPV alone appears to be insufficient as the sole cause of
HNSCC; this may explain the long latency period between
HPV infection and
cancer development. There is now sufficient evidence for a causal role for HPV in
HNSCC. As in
cervical cancer, HPV requires oncogenes and co-factors for
tumor development. Thus, inhibition or loss of such co-factors may lead to
tumor regression. The vast amounts of epidemiological, molecular pathological and in vitro experimental data are consistent with the hypothesis that HPV does indeed have a causal role. We await final validation from animal experimentation in which regression of HPV-positive
tumors will follow from loss or inhibition of E6 and E7.