Human Papillomavirus-Induced Chromosomal Instability and Aneuploidy in Squamous Cell Cancers
Samyukta Mallick, Yeseo Choi, Alison M. Taylor, Pippa F. Cosper
Abstract
Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. CIN is defined as a continuous rate of chromosome missegregation events over the course of multiple cell divisions. CIN causes aneuploidy, a state of abnormal chromosome content differing from a multiple of the haploid. Human papillomavirus (HPV) is a well-known cause of squamous cancers of the oropharynx, cervix, and anus. The HPV E6 and E7 oncogenes have well-known roles in carcinogenesis, but additional genomic events, such as CIN and aneuploidy, are often required for tumor formation. HPV+ squamous cancers have an increased frequency of specific types of CIN, including polar chromosomes. CIN leads to chromosome gains and losses (aneuploidies) specific to HPV+ cancers, which are distinct from HPV- cancers. HPV-specific CIN and aneuploidy may have implications for prognosis and therapeutic response and may provide insight into novel therapeutic vulnerabilities. Here, we review HPV-specific types of CIN and patterns of aneuploidy in squamous cancers, as well as how this impacts patient prognosis and treatment.