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Researchers find genetic alterations in head and neck cancers associated with HPV infection, smoking
Researchers at the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health (NIH), working as part of a team of scientists with The Cancer Genome Atlas (TCGA) Network, have discovered genomic differences 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.
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 for the roles that HPV infection and smoking play in head and neck cancer risk and disease development, and may 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 online January 28, 2015, in the journal Nature.
“These findings provide new insights about head and neck cancers, and how we can develop new treatments to target specific molecular pathways,” said Carter Van Waes, M.D., Ph.D., TCGA co-author and chief of the NIDCD Head and Neck Surgery Branch.
In the study, researchers performed genomic analyses on 279 tumors—head and neck squamous cell carcinomas (HNSCC)—from untreated patients. Approximately 80 percent of tumor samples were from individuals who smoked. The majority of samples were oral cavity cancers (61 percent) and larynx cancers (26 percent).
While only about 25 percent of head and neck cancers are linked to HPV infection, TCGA researchers confirmed that many patients with HPV-associated tumors have specific alterations of certain genes, which are also found in a much broader set of mutations in smoking-related tumors. Such insights may help in developing potential therapies and biomarkers, researchers noted.
Scientists also found that more than 70 percent of head and neck cancers had alterations in genes for certain growth factor receptors, signaling molecules, and cell division regulation. These genes may play roles in pathways that control cell growth and proliferation, and for which therapies are either available or in development.
The investigators also discovered new clues about drug resistance in head and neck cancers. They found that genes affecting about 40 percent of such cancers form key parts of a pathway that helps determine cell survival and drug resistance.
Head and neck cancers comprise a constellation of tumors of the mouth, throat, larynx, nasal cavity, salivary gland, and elsewhere that have frequently been attributed to tobacco and alcohol use in most patients. Some 90 percent of head and neck cancers are squamous cell carcinomas, which occur in the surface layers of cells in the body. An estimated 55,000 people developed head and neck cancer in the U.S. in 2014. Approximately 12,000 Americans die from the diseases each year. Head and neck cancers are common worldwide, with more than 600,000 cases diagnosed each year.
The findings showed similarities between head and neck cancer genomes and other cancers, including squamous cell lung and cervical cancer, indicating possible common paths of cancer development, and potential treatment opportunities. Previous research conducted by the TCGA Network also identified a characteristic molecular pattern shared by head and neck, lung, and some bladder cancers.
The TCGA Research Network has generated data and published analyses on a number of cancers, all of which can be found on the TCGA website. TCGA-generated data are freely available at the TCGA Data Portal and the Cancer Genomics Hub (CGHub).
This work was supported by the following NIH grants: P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, RO1 CA 095419, and the National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Projects ZIA-DC-000016, 73 and 74. Additional funding was provided by the Bobby F. Garrett Fund for Head and Neck Cancer Research.