Unfinished Business in Classifying HPV-Positive Oropharyngeal Carcinoma: Identifying the Bad Apples in a Good Staging Barrel

This commentary highlights three important findings in the study by Vijayvargiya et al, published in this journal, involving 9554 oropharyngeal cancer patients from the SEER database. Firstly, there is improved performance in outcome prediction with TNM-8 in HPV+ OPC. However, heterogeneity exists, especially in TNM-8 stage I disease, and there is need for ongoing improvement in risk stratification. Several anatomical and non-anatomical prognostic factors have been proposed. Among them, radiologic extranodal extension has emerged as one of the promising parameters to be considered for future staging. These baseline prognostic factors should address sensitivity, specificity, and diagnostic accuracy to serve different clinical needs. Secondly, cure is possible for some patients presenting with M1 disease. Optimal management of such patients remains to be explored, and clinical trials targeting de novo M1 disease should be encouraged to optimize outcomes for this subset. Finally, methodologies to address missing tumor HPV status in historical cohorts have been discussed, including using baseline demographics and clinical characteristics, as well as statistical procedures such as multiple imputation.