ORLANDO, FL—Patients with advanced oropharyngeal cancer and human papillomavirus (HPV) infection have better outcomes than those with HPV-negative oropharyngeal tumors, researchers reported here at the ASCO meeting.
An analysis of data from the randomized Radiation Therapy Oncology Group (RTOG) 0129 trial showed that HPV-positive patients had less than half the risk of dying from their cancer at five years than HPV-negative patients did, after controlling for other risk factors.
“Similarly, HPV-positive patients had about half the risk of tumor progression or death,” said Maura L. Gillison, MD, PhD, Professor of Internal Medicine & Epidemiology in the Division of Hematology & Oncology at Ohio State University Comprehensive Cancer Center.
Oropharyngeal cancers can be divided into two main groups: those caused by tobacco and alcohol use; and those caused by HPV infection. Previous data have suggested that the HPV status of a patient's tumor might have prognostic implications, but those analyses are limited as they did not control for other favorable prognostic factors, she said.
“HPV-positive patients tend to be younger, have smaller tumors, and have better performance status. So the better survival in this patient population may be explained by these factors and not by HPV,” Dr. Gillison explained.
To clarify the prognostic significance of tumor HPV status in patients with oropharyngeal cancer, she and her colleagues reviewed data from the RTOG 0129 trial of 721 patients. Of those, 60% had cancer of the oropharynx and 64% were HPV-positive, as determined by HPV16 in situ hybridization.
In the randomized Phase III trial, patients were stratified by primary tumor site, severity of neck metastasis, and performance status. They were then randomized to standard radiotherapy in 35 treatments over seven weeks plus cisplatin (100 mg/m2 on Days 1, 22, and 43), or accelerated radiotherapy by concomitant boost in 42 treatments over six weeks plus cisplatin (100 mg/m2 on Days 1 and 22).
The final analysis involved 206 HPV-positive patients and 117 HPV-negative patients. “Results showed that HPV status was markedly associated with overall survival. HPV-positive patients had a two-year overall survival rate of 88%, compared with 66% for HPV-negative patients,” Dr. Gillison reported.
The two-year progression-free survival rates were about 72% in HPV-positive patients versus 51% in HPV-negative patients. At five years, the overall survival rate was 77% in HPV-positive patients versus 48% for HPV-negative patients.
Overall, patients with HPV-positive oropharyngeal cancer were 59% less likely to die and 46% less likely to progress or die, compared with HPV-negative patients. In multivariate analysis that controlled for other prognostic factors and type of treatment, the results were basically unchanged, she said.
“Tumor HPV status is a strong and independent predictor of survival for patients with oropharynx cancer. The improved outcomes are due in part to lower recurrence rates in the radiation field, but not distant metastases.”
As a result of the findings, RTOG will now be stratifying patients in clinical trials by HPV status, she said, adding that clinical trials may also start to be designed specifically for HPV-positive or HPV-negative patients.
HPV Status Evaluation May Become Routine
Several oncologists told OT that due to the prognostic implications, tumor HPV status evaluation may soon become part of routine clinical care, and may also influence treatment choices in the future.
For example, ASCO President Douglas W. Blayney, MD, Professor and Medical Director of the University of Michigan Comprehensive Cancer Center, said, “This well-conducted study again speaks to the issue of personalized cancer care. We have HPV-positive and HPV-negative associated cancers, and HPV-positive tumors have the better prognosis. One can think of it as two different cancers that need to be treated differently.”
And ASCO's Immediate Past President, Richard L. Schilsky, MD, Professor of Medicine and Associate Dean for Clinical Research at the University of Chicago, said, “We often find that tumors with a viral basis have a better prognosis.” He cited nasopharyngeal tumors that are positive for Epstein-Barr virus as an example.
“We're not sure why, but probably the virus responsible for causing the cancer also causes it to behave in a more indolent fashion,” he said.