Author: Alice Goodma
Mounting evidence suggests that human papillomavirus (HPV)-positive oropharyngeal cancer has an improved prognosis compared with HPV-negative disease. The most recent supportive evidence comes from an analysis of a Phase III trial presented at the 2009 annual meeting of the American Society of Clinical Oncology.
Our study 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 lead author Maura Gillison, MD, PhD, Professor of Hematology and Oncology, Epidemiology, and Otolaryngology at Ohio State University in Columbus. Dr. Gillison said that tumor HPV status should now be part of the routine workup of patients with oropharyngeal cancers.
Oropharyngeal cancers are mainly attributable to chronic tobacco use and smoking, or to HPV infection. Retrospective analyses, meta-analysis, and small trials have suggested that HPV-positive oropharyngeal cancer is a distinct entity, and the present Phase III study provides the most compelling evidence, she said, because it is the largest study to date.
It is not clear why HPV-associated oropharyngeal cancer has a better prognosis. In the trial, HPV-positive patients were younger, mostly Caucasian, and had improved performance status and smaller tumors. Dr. Gillison said that these factors could have a positive influence on survival.
The retrospective correlative analysis of Radiation Therapy Oncology Group (RTOG) 0129, presented by Dr. Gillison, focused on outcome according to HPV status. The randomized study included 206 patients with cancers positive for HPV (96% were HPV 16-positive) and 117 patients with HPV-negative cancers. All patients received radiotherapy plus chemotherapy with high-dose cisplatin. At two years, significantly more patients were alive in the HPV-positive group: 87.9% versus 65.8% in the HPV-negative group. Median two-year progression-free survival was 71.8 months for the HPV-positive group and 50.4 months for the HPV-negative group.
The difference in survival favoring the HPV-positive group increased over time. By five years, a 29% difference favored those who were HPV-positive. Overall five-year survival was greater than 75% in HPV-positive patients versus less than 50% in those who were HPV-negative.
At five years, the HPV-positive group had half the risk of dying compared with the HPV-negative group, even after accounting for the effects of other factors, including type of treatment. The HPV-positive group also had about half the risk for tumor progression at five years. Additional analysis revealed that HPV-positive patients had lower two-year recurrence rates in the radiation field (13.6% vs 24.8%, respectively). At five years, second primary cancers were found in only 9% of the HPV-positive patients versus 18.5% of those who were HPV-negative.
Future trials by the oncology cooperative groups will stratify oropharyngeal cancer patients according to HPV subtype 16 status. HPV-16-positivity on immunohistochemistry was tightly correlated with HPV status and is a valid surrogate marker for HPV status, Dr. Gillison said. Trials may also be designed specifically for HPV-positive or HPV-negative patients, she commented.
A Distinct Entity
Formal discussant of the trial, Barbara Burtness, MD, of Fox Chase Cancer Center in Philadelphia, said that this study adds to the evidence that HPV-positive disease has a better prognosis, with increased sensitivity to both radiotherapy and chemotherapy.
It’s clear that HPV-induced oropharyngeal cancer arises through a different mechanism, has a different biological signature, and responds differently to radiation and chemotherapy, she said. Goals of therapy for HPV-induced oropharyngeal cancer should include increased preservation of speech and safe swallowing, she added.