Smoking Status Affects Presents of Unique Molecular Signatures in HPV-positive Throat Cancers

A pattern of mutations across several key cancer genes was found in patients with throat cancer who were exposed to both human papillomavirus (HPV) and tobacco smoke. These findings were presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium. The differences between heavy and light smokers may aid in informing the decision on treatment intensity.1

Although most patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) have an excellent prognosis for disease-free survival, smokers generally have a more dire prognosis.

This study split 66 cases of HPV-positive OPSCC into heavy smoking behavior (n = 40) and light smoking behavior (n =25) groups based on pack years history. Heavy smokers were defined as those who smoked more than 1 pack per day for 10 years or 2 packs per day for 5 years, and light smokers were those who smoked less than 10 pack years.

“Throat cancer patients who smoked and had a history of fewer than 10 pack years had significantly better disease free and overall survival rates than the heavier smoking group,” said Jose P. Zevallos, MD, MPH, FACS, assistant professor and director of oncologic research in the division of head and neck surgical oncology at the University of North Carolina, Chapel Hill, and a member of the Lineberger Comprehensive Cancer Center. “Our analyses identified several key differences in molecular mutational profiles of the 2 groups that may shape these outcomes.”

Mutation rates overall were higher for the heavy smoking group of patients with HPV-positive OPSCC. More frequently mutated genes included TP53, CDKN2A, FAT1, CASP8, NOTCH1, FGFR3, and KRAS.

“I think what is most striking is that these genes are mutated almost exclusively in smokers,” said Zevallos. “This molecular profile suggests that while HPV-positive OPSCC carcinogenesis initiates similarly, tumors in patients who smoke acquire novel mutations not traditionally associated with HPV-associated cancers.”

The heavy smokers with HPV-positive OPSCC had molecular profiles that were similar to patients with HPV-negative disease, except that their molecular markers kept characteristics of HPV-positive cancer such as frequent PIK3CA and MLL-3 mutations.

“Because HPV-positive throat cancers respond well to treatment, patients often are given the option of choosing less aggressive treatment with fewer side effects,” explained Zevallos. “Our study begins to set criteria-based changes in tumor DNA that can be used to predict more aggressive cases that should be given more intense treatment. We hope that this information will one day help to guide more personalized treatments for HPV-positive throat cancers.”

REFERENCE

1. Zevallos JP, Yim E, Brennan P, et al. Molecular profile of human papillomavirus-positive oropharyngeal squamous cell carcinoma stratified by smoking status. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 1.

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