Head-neck cancer therapy has become more aggressive, with the addition of chemotherapy and EGFR inhibitors to previously administrated radiotherapy. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive tonsillar and base of tongue cancer and even better for patients with favorable characteristics and biomarkers, suggesting therapy could be de-escalated for some patients, decreasing side-effects. For this purpose we combined several biomarkers and built a model to predict progression-free survival for patients with HPV-positive tonsillar and base of tongue cancer.
Patients with tonsillar and base of tongue cancer treated curatively between 2000-2011, with HPV16 DNA/E7 mRNA positive cancers also examined for CD8+TILs, HPV16 mRNA and HLA class I expression were included in the study. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set. Thereafter, the performance of the model was evaluated in the validation set.
In total, 258 patients with HPV DNA/E7 mRNA positive tumors were included in the study with 168 patients in the training set and 90 patients in the validation sets. No treatment improved survival in comparison to radiotherapy alone. CD8+ TIL counts and young age were the strongest predictors of survival. They were followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. Furthermore, a model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set.
Combined together, CD8+ TIL counts, age, T-stage and E2 mRNA expression could predict progression-free survival for 56% of the patients with very high probability. This model could be useful for identifying patients that could be offered the possibility of randomized trials with milder treatment, with less side effects, without worsening prognosis.
1. Bersani et al. A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer, Oral Oncology, In press 2017.