Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma

There has been a gradual change in the demographics of head and neck carcinoma. Although relatively uncommon, the incidence of oropharyngeal carcinoma has been increasing despite declining tobacco consumption and contrary to a diminishing incidence of cancers at other head and neck sites. It is now clear that the incidence of human papillomavirus (HPV)-associated oropharyngeal cancers is rising, likely as a consequence of changing life styles and sexual behaviors. Many studies have contributed to understanding the characteristics of HPV-related oropharyngeal carcinoma, which usually presents as nonkeratinizing squamous cell carcinoma of low to intermediate T-category and affects middle-aged white men, having higher socioeconomic status and no or brief history of tobacco consumption. The diagnosis of this distinct neoplastic entity can be firmly established by a combination of p16 immunohistochemical and in situ hybridization assays. Compared with the traditional smoking-associated head and neck squamous cell carcinoma, HPV-related oropharyngeal carcinoma has a favorable natural history and responds better to treatment. Consequently, patients with this cancer have better long-term survival than those with HPV-unrelated head and neck squamous cell carcinoma (eg, 5-year overall survival rate of >80% versus ∼40% for patients with stage III-IV tumors), and hence they are more likely to experience chronic therapy-induced morbidity. Therefore, changes in evaluation, staging, and treatment are needed for this patient group. However, attempts to change the treatment for HPV-associated oropharyngeal carcinoma should take place in a closely monitored clinical trial setting. In this article, we summarize the epidemiology, diagnosis, and clinical behavior of HPV-associated oropharyngeal carcinoma, with emphasis on prognostic and biomarker discovery aspects, and discuss briefly the current thoughts on changing the treatment paradigms aimed at reducing morbidity while preserving the high tumor control probability through well-coordinated prospective trials.