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

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.

Genetically engineered mouse model of HPV16 E6-E7 with vaginal-cervical intraepithelial neoplasia and decreased immunity

“…This process is essential for cancer maintenance because telomeres are shortened with repeated gene replication and cell division [ 24 ]. The higher the telomerase activity, the less susceptible the tumor cells are to shortened telomere-related DNA damage [ 25 ]. Our study found out that E6 and E7 expression may affect the telomere pathway and cause intraepithelial neoplasia I-II.…”