BackgroundThe study aimed to analyze the relationship between the dynamic systemic immune inflammation index (SII), human papillomavirus (HPV) infection, and the prognosis of oropharyngeal cancer patients.MethodWe retrospectively obtained the data for 131 patients treated with curative treatments and calculated their SII values based on results acquired approximately 9 months after the first treatment. The entire cohort was divided into groups according to dynamic SII and HPV infection, and their prognoses were compared.ResultsThe high SII group, particularly the persistently high SII group, had a poor prognosis, and static SII levels cannot fully reflect the prognosis of patients with oropharyngeal cancer. In HPV− patients, unfavorable dynamic SII and the site of tumor locating at the tongue base were all significantly associated with decreased disease-free survival. In contrast, no characteristic was presented as a poor prognostic factor for disease-free or overall survival in HPV+ patients.ConclusionDynamic SII values are more comprehensive prognostic indicators for oropharyngeal cancer patients, particularly HPV− patients. It could imply that an HPV− oropharyngeal cancer patient who experienced unfavorable dynamic changes in SII should receive more frequent tests or more advanced therapies.