NEW YORK (Reuters Health) – A genetic signature that distinguishes node-negative from node-positive p16-positive human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas may help optimize treatment.
P16 immunohistochemical analysis for tumor stratification is becoming common, Dr. Wesley H. Stepp of the University of North Carolina, Chapel Hill, and colleagues noted in JAMA Otolaryngology-Head & Neck Surgery, online April 18. But, they add, “Not all p16-positive tumors have excellent outcomes,” and “a more refined molecular analysis of tumors could be beneficial for treatment stratification.”
Dr. Stepp told Reuters Health by email, “we hope this type of personalized-medicine approach will improve patient outcomes. In part, by reducing toxicity of therapies like chemo or radiation by giving lower doses when a tumor’s profile appears less aggressive using our profile.”
“The converse is true as well,” he added, “meaning we can identify more aggressive cancers earlier and can treat them more effectively based on a biopsy close to when they present to the doctor.”
The researchers examined tissue specimens from six patients with node-negative disease and 15 with node-positive disease.
Overall, 146 genes were significantly different between the groups. The researchers developed a genetic signature based on 15 of these genes.
The tool had a sensitivity of 88.2% and a specificity of 85.7%. Its positive likelihood ratio was 6.1 and the negative likelihood ratio was 0.1.
Given a prevalence of node-positive disease of 70.8%, the positive-predictive value was 93.7% and the negative predictive value was 75.0%.
The team also developed a signature using a 40-gene profile that distinguishes node-negative disease from node-positive disease (area under the curve, 0.93).
“Some oncology fields are already starting to employ this type of technology, so I think we are right at the precipice on making this a reality in head and neck oncology,” Dr. Stepp said.
Dr. Arun Sharma, who wrote an accompanying editorial, told Reuters Health by email that the study “demonstrates the ability to develop a gene signature to predict outcomes in patients with HPV-positive oropharyngeal cancer. Further work with gene-expression profiling of these cancers has the potential to provide personalized information to determine prognosis and guide treatment.”
In his editorial, Dr. Sharma, of Southern Illinois University School of Medicine, in Springfield, points out, “An ideal study would develop a gene signature in one set of patients and then validate it in a second set of patients. This strategy has been used previously to develop a prognostic gene expression signature in patients with cancer and could be used in future studies.”
The study had no commercial funding. Dr. Stepp has a related patent pending submission.
SOURCE: https://bit.ly/2rbcJDw and https://bit.ly/2jguJZK
JAMA Otolaryngol Head Neck Surg 2018.
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