Radiogenomics examines associations between imaging phenotypes and underlying biological characteristics across cancer types. This structured narrative review focuses on oropharyngeal squamous cell carcinoma (OPSCC) and evaluates how genomic programs characteristic of HPV-positive and HPV-negative tumors have been investigated across computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) as variations in heterogeneity, diffusion patterns, perfusion and metabolic activity. A structured literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science to identify studies on radiomics and radiogenomics in OPSCC and related head and neck cancers. After screening and eligibility assessment, 81 studies were included in the narrative synthesis. The reviewed literature indicates that imaging-derived features have been associated with HPV status, hypoxia-related signatures, extranodal extension and treatment outcomes. However, the current evidence base remains heterogeneous and is largely composed of retrospective, single-institution studies with relatively small cohorts. Methodological challenges, including variability in imaging acquisition, segmentation and feature harmonization, limit reproducibility and generalizability. Although cone-beam computed tomography (CBCT) is not used for primary OPSCC staging and no CBCT-based radiogenomic studies in OPSCC have been reported, existing radiomics research in dentomaxillofacial imaging suggests its potential as a hypothesis-generating modality for future investigation. Overall, current evidence supports the biological plausibility of radiogenomic imaging signatures in OPSCC, while emphasizing the need for larger multicenter datasets, standardized imaging protocols and prospective validation before clinical implementation.
Barioni et al. (Tue,) studied this question.