Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma

SIMPLE SUMMARY: Human Papilloma Virus (HPV) is known to affect thousands globally. HPV infection can act carcinogenically on host cells with expression of the virus’s E6 and E7 oncoproteins. Within the United States, roughly 70% of oropharyngeal cancers are thought to be HPV induced. Viral genome integration has been well studied, yet genomic effects of the E6 and E7 proteins on other genetic regions remain relatively unidentified. This study characterizes genomic mutation in HPV-infected HNSCC patients with specific regard to host E6 and E7 expression. Individuals with greater presence of these oncoproteins were found to exhibit a greater average of point mutations, particularly on chromosomes 1, 11, and 17. Greater expression of E6 and E7 also correlates to a lesser number of clustered variation events and fewer repeats of copy number segments. Analysis of the genomic effects of HPV may provide additional insight into the pathogenesis of HNSCC. ABSTRACT: Human Papilloma Virus (HPV) is highly prevalent within the U.S., with studies estimating that over 80% of individuals will contract the virus in their lifetime. HPV is considered a primary risk factor for the development and progression of oropharyngeal cancers. The impact of the HPV virus’s E6 and E7 oncoproteins on cellular signaling pathways and genomic integration has been extensively characterized. Indirect genomic effects; however, remain relatively unidentified. In this study, we analyzed 83 HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) patients of varying HPV types. Expression counts of the HPV E6 and E7 oncogenes were estimated across samples and correlated with genomic mutational classes. High expression of E6 and E7 oncoproteins was associated with a greater number of total point mutations, especially on chromosomes 1, 11, and 17, which have been implicated in HPV-mediated cancers in previous studies. Samples with high E6 and E7 expression also exhibited more frequent non-clustered structural variation and a lack of clustered variation altogether. Copy number segments were present with fewer number of repeats in high E6 and E7 expression samples, which is known to correlate with decreased expression of affected genes. E6 and E7 expression was associated with increased activity of several cellular pathways associated in oncogenesis and telomere maintenance. In comprehensively characterizing the effects of the HPV oncoproteins on the human genome, potential mechanisms of HNSCC pathogenesis may be further elucidated.