Background: Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics‐based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients.Methods: We searched bibliographic databases (MEDLINE, Embase, Web of Science) from 2010 to 2021 and considered 31 studies with pre‐defined inclusion criteria. We followed the CHARMS checklist for data extraction and performed quality assessment using the PROBAST tool. We conducted a meta‐analysis to estimate the accuracy of the prediction and prognostic models using the diagnostic odds ratio (DOR) and average C‐statistic, respectively.Results: Manual segmentation method followed by 40% of the maximum standardised uptake value (SUV_max) thresholding is a commonly used approach. The area under the receiver operating curves of externally validated prediction models ranged between 0.60–0.87, 0.65–0.86 and 0.62–0.75 for overall survival, distant metastasis and recurrence, respectively. Most studies highlighted an overall high risk of bias (outcome definition, statistical methodologies and external validation of models) and high unclear concern in terms of applicability. The meta‐analysis showed the estimated pooled DOR of 6.75 (95% CI: 4.45, 10.23) for prediction models and the C‐statistic of 0.71 (95% CI: 0.67, 0.74) for prognostic models.Conclusions: Both prediction and prognostic models using clinical variables and PET radiomics demonstrated reliable accuracy for detecting adverse outcomes in HNSCC, suggesting the prospect of PET radiomics in clinical settings for diagnosis, prognosis and management of HNSCC patients. Future studies of prediction and prognostic models should emphasise the quality of reporting, external model validation, generalisability to real clinical scenarios and enhanced reproducibility of results.

High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck squamous cell carcinoma (HNSCC). Using 124 PET radiomics features and clinical variables (age, sex, stage of cancer, site of cancer) from a cohort of 232 patients, we evaluated four survival models—penalized Cox model, random forest, gradient boosted model and support vector machine—to predict all-cause mortality (ACM), locoregional recurrence/residual disease (LR) and distant metastasis (DM) probability during 36, 24 and 24 months of follow-up, respectively. We developed models with five-fold cross-validation, selected the best-performing model for each outcome based on the concordance index (C-statistic) and the integrated Brier score (IBS) and validated them in an independent cohort of 102 patients. The penalized Cox model demonstrated better performance for ACM (C-statistic = 0.70, IBS = 0.12) and DM (C-statistic = 0.70, IBS = 0.08) while the random forest model displayed better performance for LR (C-statistic = 0.76, IBS = 0.07). We conclude that the ML-based prognostic model can aid clinicians in quantifying prognosis and determining effective treatment strategies, thereby improving favorable outcomes in HNSCC patients.