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Researchers 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.
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, 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.
“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, which
is the part 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—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 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 Dr. Hayes.
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 are squamous cell
carcinomas, which occur in the surface layers of
cells in the body.
Scientists found that more than 70 percent of head
and neck cancers had alterations in genes for growth
factor receptors (EGFR, FGFR, IGFR, MET, ERBB2,
DDR2), signaling molecules (PIK3CA, HRAS) and cell
division regulation (CCND1). 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. They
showed that extra copies of the genes FADD and
BIRC2, or mutations in or the absence of the
CASP8gene in smoking-related cancers — all which
affect the process of programmed cell death — may
underlie the resistance of cancer cells to current
treatments. Similarly, the absence of the TRAF3
gene, or extra copies of a gene for the
growth-promoting E2F1 protein in HPV-related cancers,
may also increase resistance.
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.
For more information
Nature
Comprehensive genomic characterization of head and
neck squamous cell carcinomas
U.S. National Institute on Deafness and Other
Communication Disorders
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