Radiological Features of Human Papillomavirus (HPV)-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma...

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative OPSCC in its molecular, biological, and clinical characteristics. We reviewed the literature on radiological differences between HPV-positive and HPV-negative OPSCC across ultrasound, CT, MRI, and PET-CT as this appears to be a critical gap in the literature. Methods: We performed a narrative review of studies reporting imaging findings in OPSCC by HPV status. Two reviewers independently searched PubMed, Ovid MEDLINE, Ovid EMBASE, and the Cochrane Library, from inception to February 2026, supplemented by searching major radiology journals and the grey literature. Eligible English-language studies included patients with OPSCC of known HPV status, assessed at least one imaging modality, and reported imaging findings stratified by HPV status. After title, abstract, and full-text screening, 66 studies were included. Results: HPV(+) OPSCC was more commonly associated with well-defined primary tumours and a higher prevalence of nodal metastases, particularly cystic nodal metastases and extranodal extension. These findings were broadly concordant with reported radiomic signatures. MRI studies suggested lower apparent diffusion coefficient values, while PET-CT studies suggested higher entropy and smaller primary lesions in HPV-positive disease. Conclusions: Selected imaging features may help distinguish HPV(+) from HPV(-) OPSCC, but current evidence remains insufficient for reliable standalone clinical application. Prospective multicentre validation and integration of multimodal imaging, radiomics, and radiogenomics are needed to improve non-invasive HPV stratification and support future precision diagnostics.