Study Identifies Prognostic Biomarker in HPV-Related Head and Neck Cancers
A study investigating how to identify and treat patients with high- and low-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has demonstrated variations in HPV-related molecules among HPV-positive cases of the disease. Using their findings, the investigators developed a prognostic biomarker signature for identification of this subgroup of patients. The findings could translate to improved patient stratification to reduce treatment intensity and treatment toxicities, as well as lead to new therapeutic approaches for treatment-resistant HPV-related cancer. The study by Gleber-Netto et al was published in JCI Insight.
According to the Centers for Disease Control and Prevention, each year, over 18,000 people are diagnosed with oropharyngeal cancer. About 70% of those cases are caused by HPV. Although standard care for HPV-positive oropharyngeal cancers (consisting of combination chemotherapy and radiation therapy) is successful in achieving a 5-year survival rate of about 85%—compared to only 55% for HPV-negative cancers—patients often suffer from permanent radiotherapy-related morbidity, including problems with speech and swallowing.
Study Methodology and Findings
The researchers analyzed data from 80 oropharyngeal cancers in The Cancer Genome Atlas. Instead of classifying tumors as HPV-positive or HPV-negative, the researchers examined all tumors based on their level of HPV gene expression.
The researchers found an initial panel of 582 HPV-correlated genes that distinguished three subgroups: a high-HPV group, a low-HPV group, and an HPV-negative group. Each group had statistically significant survival differences. Additional analysis led to a panel of 38 genes that are able to distinguish between the two HPV-positive subgroups.
A variety of genetic analyses confirmed the distinction between the HPV-positive subgroups, and the researchers discovered two viral genes generally not thought to be important for tumor progression that were significantly different between these subgroups. In addition, cell-line studies showed these genes to be correlated with radiation sensitivity.
Finally, the researchers developed a prognostic biomarker signature for identification of this subgroup of HPV-positive oropharyngeal squamous cell carcinoma and validated it in independent patient cohorts of HPV-related oropharyngeal and cervical carcinomas. In each case, the gene panel appeared to be prognostic of survival and performed better than available clinical factors, such as smoking status and tumor size.
The “findings could translate to improved patient stratification for treatment deintensification and new therapeutic approaches for treatment-resistant HPV-related cancer,” concluded the study authors.
Clinical Significance
“Patients with HPV-positive oropharyngeal tumors are living a long time after radiation treatment, but often are left with significant long-term morbidity, including problems with speech or swallowing,” said Curtis R. Pickering, PhD, Assistant Professor of Head and Neck Surgery at The University of Texas MD Anderson Cancer Center and a coauthor of this study. “Therefore, there’s a desire among clinicians to reduce, or de-escalate, therapy to lessen severe side effects. However, we currently don’t have good biomarkers to safely determine which patients are candidates for de-escalation…. What I’m hoping is we’ve found some new fundamental aspects of HPV biology related to the carcinogenic process, the progression of the tumor, and response to therapy. If we’re able to validate this in future studies, it could be incredibly clinically useful across several HPV-related tumor types.”
Dr. Pickering is the corresponding author of this study.
Disclosure: Funding for this study was provided by the National Institutes of Health, the National Cancer Institute, and the HPV-Related Cancers Moon Shot. The study authors’ full disclosures can be found at insight.jci.org.
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®.
