Subsite-specific benefit of induction chemoimmunotherapy in HPV-negative oropharyngeal squamous cell carcinoma

To evaluate whether the addition of immune checkpoint inhibitors (ICIs) to induction chemotherapy improves outcomes in HPV-negative oropharyngeal squamous cell carcinoma (OPSCC), and whether efficacy differs by primary tumor subsite.

We retrospectively analyzed 99 patients with newly diagnosed HPV-negative OPSCC treated with induction therapy followed by definitive chemoradiotherapy. Patients received induction chemotherapy alone (IC; n = 73) or IC plus ICI (n = 26). Progression-free survival (PFS) was the primary end point and overall survival (OS) was secondary. Propensity score matching (PSM) was used to adjust for baseline imbalances. Subgroup analyses were performed for base-of-tongue (BOT) and non-BOT tumors.

In the overall cohort, IC+ICI was associated with numerically improved PFS and OS, but differences were not statistically significant before or after PSM. In the non-BOT cohort, IC+ICI was associated with significantly improved PFS both before and after PSM. Before matching, 24- and 36-month PFS rates were 100% and 100% with IC+ICI versus 74.0% and 68.9% with IC; after matching, the corresponding rates were 100% and 100% versus 77.0% and 72.9%, respectively. OS did not significantly differ, although outcomes consistently favored IC+ICI. In the BOT cohort, neither PFS nor OS differed significantly between groups.

In HPV-negative OPSCC, adding ICI to induction chemotherapy showed numerically favorable but statistically non-significant PFS and OS differences in the overall cohort. Exploratory subgroup analyses suggested a potential immunotherapy-related benefit in patients with non-BOT primary tumors, warranting prospective validation.