Genetic Landscape of Human Papillomavirus-Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors

Abstract

Head and neck cancer is the fifth most common cancer worldwide. It is often amenable to curative intent therapy when localized to the head and neck region, but it carries a poor prognosis when it is recurrent or metastatic. Therefore, initial treatment decisions are critical to improve patient survival. However, multimodality therapy used with curative intent is toxic. The balance between offering intensive versus tolerable and function-preserving therapy has been thrown into sharp relief with the recently described epidemic of human papillomavirus-associated head and neck squamous cell carcinomas characterized by improved clinical outcomes compared with smoking-associated head and neck tumors. Model systems and clinical trials have been slow to address the clinical questions that face the field to date. With this as a background, a host of translational studies have recently reported the somatic alterations in head and neck cancer and have highlighted the distinct genetic and biologic differences between viral and tobacco-associated tumors. This review seeks to summarize the main findings of studies, including The Cancer Genome Atlas, for the clinician scientist, with a goal of leveraging this new knowledge toward the betterment of patients with head and neck cancer.

Fig 1.

Role of E6 and E7 in the cell cycle pathways and gene alterations as a function of human papillomavirius (HPV) tumor status. Genes altered in HPV-positive or viral oncogenes (red) or in HPV-negative tumors (black). RB, retinoblastoma tumor-suppressor protein.

Fig 2.

Copy number alterations by chromosome position in human papillomavirus (HPV) –positive and HPV-negative tumors.

Fig 3.

Frequent genetic aberrations in selected pathways altered in HPV-positive (A) and HPV-negative (B) head and neck squamous cell carcinoma. Overview of key genetic aberrations for HPV-positive and HPV-negative head and neck cancers. Shades of gold indicate frequency of activating changes in presumed oncogenes, and shades of blue indicate frequency of inactivating changes in presumed tumor suppressor genes. amp, amplification; del, deletion; HLA, human leukocyte antigen; mut, mutation; fus, fusion/translocation; wt, wild type.