ABSTRACT Objective To determine whether adolescent and young adult (AYA) oral cancer represents a clinically recognizable subset and to explore age-associated differences in tumor-infiltrating T-cell states. Methods We retrospectively compared clinicopathologic characteristics between AYA and non-AYA patients with oral cancer treated at our institution, focusing on primary tumor subsite, gross growth pattern, and clinically recognizable leukoplakic change around the primary lesion. Tumor-infiltrating T-cell populations were also examined by immunofluorescence, with attention to CD4 + and CD8 + cell infiltration, GZMK + CD8 + cytotoxic T lymphocytes, and PD-1/LAG-3 expression within the CD8 + compartment. Results A total of 754 patients were included, comprising 43 AYA and 711 non-AYA patients. The tongue was markedly overrepresented in the AYA group (79.1% vs. 52.2%), whereas stage distribution was similar between groups. Although overall survival was not worse in AYA patients, disease-free survival tended to be poorer in the AYA group. Among tongue cancers, endophytic growth was more frequent in AYA patients, and AYA tumors more often presented with little surrounding leukoplakic change. Non-AYA tumors tended to show greater CD4 + and CD8 + T-cell infiltration. GZMK + CD8 + cells were detected in both groups, whereas PD-1 and LAG-3 expression appeared more prominent in non-AYA tumors. Conclusions AYA oral cancer appears to constitute a clinically recognizable subset characterized by tongue predominance and an endophytic, non-leukoplakic presentation, without inferior overall survival. At the same time, the tendency toward poorer disease-free survival suggests that AYA oral cancer may differ from older-onset disease in recurrence-related clinical behavior. Age-associated differences may also extend to the local immune microenvironment and may have implications for age-stratified immune profiling in oral cancer.
Zhang et al. (Mon,) studied this question.