ASCO: HPV status predicts survival, progression of oropharyngeal cancer

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Patients with stage III or IV oropharyngeal cancer whose tumors contain the human papillomavirus (HPV) have better outcomes than patients with HPV-negative disease, according to research from the Radiation Therapy Oncology Group (RTOG) presented Saturday at the 2009 American Society of Clinical Oncology (ASCO) meeting in Orlando, Fla.

"Our findings showed that HPV status is as strong a predictor of outcome as cancer stage for patients with oropharyngeal cancers, even after considering other factors such as age and smoking history," said the study's lead author Maura Gillison, MD, PhD, professor of medicine, epidemiology and otolaryngology at Ohio State University in Columbus. "We're still not entirely sure why this is, but these data provide further evidence that HPV-positive oropharyngeal cancer (OPC) is a distinct disease entity."

Previous smaller studies have suggested that patients with HPV-positive oropharyngeal tumors fare better than their HPV-negative counterparts. But patients with HPV-positive oropharyngeal cancer also tend to be younger, have a smaller tumor at diagnosis, and are less likely to smoke than HPV-negative patients. This is the first study large enough to consider HPV together with these other factors in patients who received the same therapy in a large clinical trial.

In the RTOG phase III clinical trial, Gillison and her colleagues compared the progression-free survival (PFS) and overall survival between 206 patients with oropharyngeal cancer containing HPV (mostly HPV subtype 16) and 117 patients with HPV-negative cancers; all patients received a combination of radiation therapy and chemotherapy.

At two years, 87.9 percent of HPV-positive patients were still alive, compared with 65.8 percent of HPV-negative patients. Two-year, progression-free survival (PFS) for the groups was 71.8 percent and 50.4 percent, respectively. The incidence of second primary cancers among HPV-positive patients was less than half that of HPV-negative patients at five years: 9 percent versus 18.5 percent.

"Tumor HPV status is strongly associated with OS/PFS among OPC patients receiving standard of care chemo-radiation, and should now be a stratification factor for all clinical trials including OPC cases, and separate trials based on tumor HPV status should be considered," the authors wrote.

Gillison noted that the association between HPV and head and neck cancers is already changing the way clinical trials are designed, with investigators stratifying patients by HPV status. Other studies are being designed to assess the efficacy of the HPV vaccine for the prevention of these cancers.

"When this study began accruing patients seven years ago we had no idea that HPV status would play a critical role in predicting outcome for head and neck cancer patients," said Walter J. Curran, Jr., MD, the RTOG chair, and chief medical officer of the Emory Winship Cancer Institute in Atlanta. "However, RTOG has made it a priority to prospectively collect material for future marker analyses and, after several small studies began to show a correlation between HPV status and outcome for head and neck cancer patients, Dr. Gillison and her team were able to quickly analyze the tumor specimens banked for this study and correlate them with outcomes data."

RTOG, a U.S. clinical trials group funded by the National Cancer Institute (NCI), is a clinical research component of the American College of Radiology (ACR).