Association of HPV/p16 status with post-test disease risk after [18F]FDG PET/CT in oropharyngeal squamous cell carcinoma: A systematic review and meta-analysis

Post-treatment [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) guides response assessment after definitive (chemo)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC), but its clinical meaning may differ by human papillomavirus (HPV)/p16 status. PubMed/MEDLINE, Scopus, and Web of Science were searched through 14 July 2026 for studies reporting post-treatment PET/CT outcomes with HPV/p16 information. Early residual disease, later failure or recurrence, equivocal findings, second-look PET/CT, and later surveillance were analysed separately. Internal HPV/p16-stratified comparisons were pooled as random-effects risk ratios with Hartung-Knapp-Sidik-Jonkman confidence intervals. Thirty-three reports, representing approximately 24 cohort families, were included; three predominantly OPSCC cohorts contributed to the primary comparison. After a positive or less-than-complete first PET/CT, subsequent disease risk was not demonstrably different between HPV/p16-positive and HPV/p16-negative disease (risk ratio 0.53, 95 % confidence interval 0.08–3.38; I 2 = 75.8 %). After a negative or complete-response scan, risk was lower in HPV/p16-positive disease (risk ratio 0.23, 95 % confidence interval 0.07–0.74; I 2 = 0 %). Early studies consistently reported high negative predictive values but heterogeneous positive predictive values. Event rates after equivocal findings ranged from 11.8 % to 72.7 %. In selected cohorts, 30.7–70.7 % of incomplete responses converted to complete metabolic response on second-look PET/CT. HPV/p16 status appeared to modify post-test risk more consistently than intrinsic PET discrimination. Negative scans were associated with lower subsequent disease risk in HPV/p16-positive OPSCC. Given the few direct comparisons and heterogeneous methods, positive or equivocal findings require cautious, context-specific interpretation; fixed HPV/p16-specific management algorithms are not supported.