Study Finds Combining a Novel Biomarker With HPV Status Predicts Patient Outcome in Head and Neck Cancer
Using next-generation sequencing and the clinical data of patients with head and neck squamous cell carcinoma, researchers found that combining mutant-allele tumor heterogeneity as a biomarker with patients’ human papillomavirus (HPV) status provides a reliable predictor of patient survival. The study by Rocco et al was presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
Researchers examined exome next-generation sequencing data and associated clinical patient data from several institutions made available to them through The Cancer Genome Atlas (TCGA). The TCGA data included information on 305 patients with head and neck squamous cell carcinoma; 35 of the patients were HPV-positive. Genetic heterogeneity of each tumor was assessed by mutant-allele tumor heterogeneity, the percentage ratio of the width to the center of the distribution of tumor-specific mutant-allele fractions.
The researchers limited their analysis to mutant-allele fractions no less than 0.075 and used the high-mutant-allele tumor heterogeneity cutoff value of 32 previously found to distinguish outcome classes. Cox proportional hazards analysis was used to evaluate the relations of mutant-allele tumor heterogeneity and HPV to overall survival.
Study Findings
The investigators’ examination confirmed that high tumor mutant-allele tumor heterogeneity at the time of surgery is an indicator of poor outcome (high mutant-allele tumor heterogeneity hazard ratio [HR] = 2.1; 95% confidence interval [CI] = 1.4–3.2; P = .0002, logrank test) and that HPV-positive patients with head and neck squamous cell carcinoma have lower average mutant-allele tumor heterogeneity values than those who are HPV-negative.
In bivariate analysis, both mutant-allele tumor heterogeneity and HPV were significantly associated with survival. When stratified by HPV status, mutant-allele tumor heterogeneity was similarly related to outcome in clinically defined subsets of patients regardless of clinical characteristics, including tumor margins, nodal classification, or tumor staging. Median follow-up with the 173 surviving patients was 22 months.
“What’s important to note is that mutant-allele tumor heterogeneity is a continuous variable,” lead author James W. Rocco, MD, PhD, Daniel Miller Chair, Associate Professor of Otology and Laryngology at Massachusetts General Hospital and Harvard Medical School, said at a news briefing. “We assign a certain value to create Cox to curves, but you can actually fine-tune the prediction of patients. In this TCGA data set, because we had four times as many patients [as in our previous study], we were able to establish that mutant-allele tumor heterogeneity could stratify the HPV-positive patients.”
The findings, said Dr. Rocco, provide opportunities to personalize therapy for HPV-positive head and neck squamous cell carcinoma patients and may help identify the patients most likely to benefit from clinical trials.
The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
