Human papilloma virus in locally advanced stage III/IV squamous cell cancer of the oropharynx and impact on choice of therapy.

Oropharyngeal cancers (OPCs) are now believed to arise from two distinct pathways: one influenced by alcohol and tobacco use and the other a result of genomic instability induced by the human papilloma virus (HPV). The incidence of HPV-associated OPC is increasing, particularly among younger males. Case series and clinical trials suggest that patients with HPV-positive OPC have better clinical outcomes than those with HPV-negative tumors. We evaluated efficacy data in published articles and meeting abstracts from clinical studies comparing response rates and survival outcomes in patients with HPV-positive and -negative locally advanced OPC. Eight clinical studies were identified: half were prospective analyses of outcome according to HPV status; the remaining four reports were retrospective analyses. The majority of these analyses showed that patients with HPV-positive tumors had significantly better responses to treatment than those with HPV-negative tumors. In the two studies in which the effect of treatment was also evaluated, patients with HPV-positive tumors did not benefit significantly from intensive therapy, unlike those with HPV-negative tumors. HPV-positive tumor status is an important prognostic factor associated with a favorable outcome in patients with locally advanced OPC. The HPV status of patients with locally advanced OPC should be established before treatment commences. Surgery is well accepted in the treatment of OPC, but the place of chemoradiotherapy has yet to be confirmed. Prospective, well-controlled clinical studies are required to establish whether chemoradiotherapy provides an acceptable risk-benefit balance versus high-quality radiotherapy alone in patients with HPV-positive OPC, in whom the goal is to maximize progression-free and overall survival, while preserving function and maintaining quality of life.