Tumor HPV Status Predicts Outcomes in Oropharyngeal Cancer

Tumor HPV Status Predicts Outcomes in Oropharyngeal Cancer

Tumor human papillomavirus (HPV) status is a strong and independent predictor of survival and disease progression for patients with oropharyngeal cancer, and this status should be a stratifying factor in future treatment studies. Research results presented at Saturday’s Head and Neck Cancer Oral Abstract Session suggested that tobacco exposure also be added as a stratification factor.

On behalf of the Radiation Therapy Oncology Group (RTOG), Maura L. Gillison, MD, PhD, of The Ohio State University, presented data from the first analysis of how tumor HPV status affects survival outcomes (Abstract 6003). The study was a prospective clinical trial of sufficient size to account for the possible influence of other prognostic factors, such as smoking history and age. Patients with HPV-positive tumors are more likely than patients with HPV-negative tumors to have several more favorable prognostic factors, such as young age or good performance status.

This correlative study was conducted on samples from patients enrolled in RTOG 0129. Investigators evaluated the association of tumor HPV status and survival in patients enrolled in a randomized phase III trial comparing standard fractionation radiotherapy plus cisplatin (100 mg/m2 on days 1, 22, and 43) to accelerated fractionation radiotherapy plus cisplatin (100 mg/m2 on days 1 and 22).

Tumor HPV status was determined by HPV16 in situ hybridization (ISH) for 323 of 433 patients (75%); 206 of 323 (64%) were HPV positive. Patients who were HPV16 negative were further tested with wide-spectrum ISH for the presence of other HPV markers. Dr. Gillison noted that p16 immunohistochemistry test results and HPV status were highly correlated. Of the patients who were HPV positive, 96% also were p16 positive. Two-year overall survival and progression-free survival rates were calculated for patients, comparing HPV-positive and HPV-negative status. Hazard ratios were adjusted for treatment assignment, age, race, T stage, N stage, and smoking (20 years or more compared with fewer than 20 pack years).

Overall survival at 2 years was 87.9% for HPV-positive patients and 65.8% for HPV-negative patients (p < 0.001). Progression-free survival was 71.8 months for HPV-positive patients and 50.4 months for HPV-negative patients (p < 0.001).

“HPV-positive patients tend to be younger, Caucasian, have better performance status, and are more likely to have T2 and T3 tumors,” said Dr. Gillison. They also have fewer pack-years exposure to tobacco compared to HPV-negative patients.

Dr. Gillison pointed out that tobacco use appears in clinical trials that include patients with oro-pharyngeal cancer.

Dr. Gillison further proposed that, although the data was “conclusive but not compelling,” three subsets should be considered for further studies: patients who are HPV positive, patients who are HPV negative, and level of tobacco exposure.

Discussant Barbara Burtness, MD, of Fox Chase Cancer Center, noted that the improved prognosis of HPV-associated oropharynx cancer in these data sets is consistent with prior retrospective reports and meta-analysis. Some studies have shown that patients with oropharyngeal cancer have increased sensitivity to radiation therapy, and others have suggested a similar effect with chemotherapy.

“It’s clear that HPV-induced oropharynx cancer arises through a different mechanism, has a different biologic signature, and responds differently to systemic and radiation therapy,” Dr. Burtness said. “In short, it’s a separate disease.”

Figure: Overall survival.