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Smoking status linked to distinct mutation patterns in HPV-positive oropharyngeal cancer
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Patients with HPV-positive oropharyngeal cancer exhibited distinct patterns of genetic mutations based on whether they were heavy smokers or light smokers, according to study results presented at the Multidisciplinary Head and Neck Cancer Symposium.
These mutation patterns may provide additional prognostic criteria to help shape treatment decisions, according to the researchers.
Jose P. Zevallos, MD, MPH, FACS
“We know that patients with exposure to both HPV and tobacco have an intermediate outcome relative to HPV-negative tobacco-driven tumors and HPV-positive tumors in never-smokers,” Jose P. Zevallos, MD, MPH, FACS, assistant professor and director of oncological research at University of North Carolina School of Medicine, said during a press briefing.
Thus, Zevallos and colleagues conducted this study to compare the genomic characteristics of HPV-positive oropharyngeal cancer according to smoking status using targeted next-generation DNA sequencing.
The analysis included 66 patients with HPV-positive oropharyngeal cancer from a North Carolina-based epidemiologic study conducted between 2001 and 2006. Forty of the patients were heavy smokers — indicating they had more than 10 pack-years — and the other 26 patients were light smokers or nonsmokers, indicating they had fewer than 10 pack-years.
Mutations associated with tobacco use occurred more frequently among heavy smokers than light smokers, which included NOTCH1 (18% vs. 0%), FAT1 (14% vs. 6%), CASP8 (8% vs. 0%), AJUBA (4% vs. 0%), TP53 (6% vs. 0%), CDKN2A (2% vs. 0%), FGFR3 (10% vs. 0%) and KRAS (4% vs. 0%).
However, HRAS mutations appeared more frequent in the light-smoker cohort (6% vs. 0%).
However, both heavy smokers and light smokers exhibited a significant number of mutations across the PI3K pathway, namely PI3KCA (34% vs. 50%) and PTEN (8% vs. 6%).
Additional data showed that 95% of the patients had HPV-16. Further, the mean number of HPV reads — 838,520 — appeared inversely related to smoking and survival status.
“This means that these tumors potentially began as HPV driven, but over time developed subclones that were driven by tobacco-associated gene mutations as a result of the exposure to smoking,” Zevallos said.
The researchers proposed that HPV-positive smokers acquire these mutations later on in carcinogenesis while maintaining their HPV-positive signature, meaning the PI3K pathway could be initiating the event.
“We think this study … will have important implications for personalizing treatment and decision-making, particularly in the era of less-aggressive treatment for HPV-positive tumors because of their excellent prognosis,” Zevallos said. “As opposed to arbitrarily deciding that 10 pack-years is a number we use to define more aggressive disease, we are trying to provide a molecular basis for more aggressive disease to decide who would benefit from less-aggressive or more-aggressive treatment.” – by Anthony SanFilippo
Reference:
Zevallos JP, et al. Abstract 2. Presented at: Multidisciplinary Head and Neck Cancer Symposium; Feb. 18-19, 2016; Scottsdale, Ariz.
Disclosure: The researchers report no relevant financial disclosures.