Alterations in head and neck cancers associated with HPV infection are found

Investigators with The Cancer Genome Atlas (TCGA) Research Network have discovered genomic differences, with potentially important clinical implications, in head and neck cancers caused by infection with the human papillomavirus (HPV).

HPV is the most common sexually transmitted virus in the United States, and the number of HPV-related head and neck cancers has been growing. Almost every sexually active person will acquire HPV at some point in their lives, according to the Centers for Disease Control and Prevention.

The researchers also uncovered new smoking-related cancer subtypes and potential new drug targets, and found numerous genomic similarities with other cancer types. Taken together, this study's findings may provide more detailed explanations of how HPV infection and smoking play roles in head and neck cancer risk and disease development, and offer potential novel diagnostic and treatment directions.

The study is the most comprehensive examination to date of genomic alterations in head and neck cancers. The results were published in Nature (2015; doi:10.1038/nature14129). TCGA is jointly supported and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health.

"The rapid increase in HPV-related head and neck cancers, noticeably in oropharyngeal tumors, has created an even greater sense of urgency in the field," said D. Neil Hayes, M.D., M.P.H, senior author of the study report and associate professor of medicine at the University of North Carolina (UNC) and the UNC Lineberger Cancer Center at Chapel Hill. Oropharyngeal cancer starts in the oropharynx, the area of the throat just behind the mouth.

"We're uncovering differences between tumors with and without HPV infection, and these new data are allowing us to rethink how we approach head and neck cancers."

In the study, researchers performed genomic analyses on 279 tumors from untreated patients with head and neck squamous cell carcinomas (HNSCC). Approximately 80% of tumor samples were from smokers. The majority of samples were oral cavity cancers (61%) and larynx cancers (26%).

While only approximately 25% of head and neck cancers are linked to HPV infection, TCGA researchers confirmed that many patients with HPV-associated tumors have specific alterations of the gene FGFR3 and mutations in the PIK3CA gene, which are also found in a much broader set of mutations in smoking-related tumors.

In contrast, while the EGFR (epidermal growth factor receptor) gene is frequently altered in HPV-negative tumors in smokers, it is rarely abnormal in HPV-positive tumors. Such insights may help in developing potential therapies and biomarkers, noted Hayes.

The findings showed similarities between head and neck cancer genomes and other cancers, including squamous cell lung and cervical, indicating possible common paths of cancer development, and potential treatment opportunities.

"It is surprising to see that head and neck tumor genomes are remarkably similar to cervical and squamous lung cancer genomes. They are from very different organs, but they show similar losses and gains of genetic material across tumors," Hayes noted. These common genetic abnormalities belong to a pathway that protects cells from damage and stress.

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