Objectives: This study aimed to compare the imaging findings associated with the recurrence of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Methods: In total, 68 patients (51 men; mean age, 64.4 years; age range, 41–86 years; 48 HPV-positive patients and 20 HPV-negative patients) with histopathologically proven OPSCC who underwent CT, MRI, and 18F-FDG-PET/CT before treatment between October 2014 and July 2022 were enrolled in this study. The imaging findings were retrospectively evaluated and statistically compared. Results: HPV-positive OPSCC had a significantly lower recurrence rate compared with that of HPV-negative OPSCC (p < 0.01). Among HPV-positive OPSCCs, patients with recurrence were considerably older than those without recurrence (p < 0.05); however, the T and N categories did not differ between the two groups. Meanwhile, among HPV-negative OPSCCs, the T and N categories were associated with recurrence (p < 0.05). Furthermore, the attenuation on contrast-enhanced CT (p < 0.05) and signal intensity on contrast-enhanced T1-weighted images (p < 0.05) of nodal metastases were significantly lower in recurrence patients compared to those in nonrecurrence patients. Cystic change in nodal metastases in HPV-positive and HPV-negative OPSCCs were similar in patients with and without recurrence. Conclusions: The T and N categories were associated with recurrence in HPV-negative OPSCC but not in HPV-positive OPSCC. Prognostic factors differed significantly between HPV-positive and HPV-negative OPSCC.
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