Risk-tailored approaches are the backbone of contemporary clinical research and treatment in oncology. Attention to risk-stratification model development, especially concerning the choice and emphasis of prognostic factors to include in a model, is essential to understanding prognosis and implementing strategies to advance treatment, e.g. selecting patients for differing treatments or strategies for exploration in clinical trials, including defining eligibility for trials and determining useful stratifications in the design of randomised controlled trials. Prognostic factors can be classified as pre-treatment factors and dynamic factors. Pre-treatment baseline factors refer to those factors that exist prior to any intervention or treatment for the setting under consideration. The outcomes of HPV-positive oropharyngeal carcinoma (HPV+ OPC) patients can be stratified based on a number of parameters, that usually include some description of smoking status, patient characteristics such as age, performance status, and conventional TNM disease stage. Emerging areas that may be considered now or in the future also include extranodal extension (ENE), baseline circulating HPV DNA (HPV-ctDNA), and TME (tumour micro-environment) among others. Dynamic factors refer to those emerging during and post-treatment. The latter concept is obviously not new and has traditionally influenced post-initial management approaches of head and neck cancer for many years, such as when making decisions based on pathological findings after surgery (e.g. pathological size, tumour extension, resection margin status and the presence of ENE status in the resected specimen). However, the current discussion will focus on important emerging strategies within the same paradigm, e.g. response to induction therapy, and changes in HPV-ctDNA. Compared to traditional smoking-related HPV-negative OPC, HPV+ OPC is a different disease with very different biological and clinical behaviour and it is important to re-appraise traditional prognostic factors as well to appreciate the clinical relevance of emerging biomarkers. This chapter summarizes updates concerning prognostic factors and risk stratification in HPV+ OPC that may realistically influence management or investigation of the disease in the short term.