Refining Evaluation Methodology on TNM Stage System: Assessment on HPV-Related Oropharyngeal Cancer

TNM stage is important in treatment decision-making and outcome predicting. The existing Oropharyngeal Cancer (OPC) TNM stages have not made distinction of the two sub sites of HPV+ and HPV- diseases. Besides that, the current TNM stage grouping is generally derived based on literature review and clinical understanding of the disease processes. It is important to have quantitative assessment on the prognostic ability and stability of the TNM stage on HPV-related OPC patients. The current stage evaluation criteria use non-parametric methods and assess the stage performance on limited time points. Even though the current stage systems were mostly developed based on retrospective data, these evaluation criteria don’t consider the important clinical confounders. We developed novel criteria to assess performance of the TNM stage grouping schemes based on parametric modeling adjusting on important clinical factors. These criteria evaluate the TNM stage grouping scheme in five different measures: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. The novel criteria were applied to evaluate newly developed TNM stage grouping schemes on HPV+ OPC patients and a few existing TNM stage grouping schemes. The new HPV+ OPC TNM stage outperforms all existing schemes on prognosis and stability.