New Genetic Factors Linked to HPV-Related Cancers

By LabMedica International staff writers
Posted on 04 Nov 2016

A new, large-scale genetic study of head and neck cancers shows why some individuals infected with human papillomavirus (HPV) may go on to develop oropharyngeal cancer while others do not.

Head and neck cancers are a related group of cancers that involve the oral cavity, pharynx (oropharynx, nasopharynx, and hypopharynx), and larynx. The most significant causes of all head and neck cancers are tobacco use and alcohol consumption. These exposures account for the development of approximately 80% of such cancers globally, with some variation for different subsites with 65% for the oral cavity versus 86% for the larynx.

Image: Immunohistochemistry image of invasive squamous cell carcinomas of tonsil tissue showing overexpression of p16, which is a very good surrogate marker for HPV infection (Photo courtesy of David C. Hoak, MD).

An international team of scientists led by those at the International Agency for Research on Cancer (IARC, Lyon, France) conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. The team conducted extensive DNA analysis of more than seven million variants for each individual. The scientists identified seven new genetic loci (locations of a gene on a chromosome): one that is linked to oropharyngeal cancer and six that are associated with oral cavity cancer, thus providing new insights into the development of these diseases.

The most prominent finding was an association between oropharyngeal cancer and genetic variation in the human leukocyte antigen (HLA) region, a genetic region important for regulation of the immune system. One particular set of variants in the HLA region was associated with a more than 4-fold protective effect against developing oropharyngeal cancer associated with HPV infection. The same genetic variants have previously been shown to protect against cervical cancer, which is known to be associated with HPV infection.

Paul Brennan, PhD, Head of IARC's Section of Genetics and a senior author of the study said, “These results indicate that genes that control the immune system play a fundamental role in influencing whether an HPV infection goes on to develop into an HPV-related cancer. Understanding why this happens may help us to identify additional methods to protect against HPV-related cancers.” The study was published on October 17, 2016, in the journal Nature Genetics.

Related Links:
International Agency for Research on Cancer