Demographic and Anatomic Features of Early-onset Oral Cavity Squamous Cell Carcinoma

Introduction: Oral cavity squamous cell carcinoma (OCSCC) is most commonly diagnosed in males aged 65-84; however, recent population-based studies have described increased incidence of OCSCC in young females. This study aims to examine the phenotypic profile of early OCSCC in a large, contemporary cohort.

Methods: A group of participants with OCSCC diagnosed 1983-2023 was generated from the National Institutes of Health All of Us database using standardized condition concept codes. Non-smoker/non-drinker (NSND) status was determined using lifestyle survey responses: non-smokers reported < 100 lifetime cigarettes, and non-drinkers reported alcohol consumption no more than 2-4 times per month.

Results: Of 1095 patients with OCSCC, 11.7% were diagnosed ≤45 years old, 44.4% were female, and 32.8% were NSND. Patients diagnosed ≤45 were 69.5% female while those diagnosed >45 were 37.3% female (p < 0.001). White patients comprised 51.6% of young-onset cases, compared to 72.7% of cases >45 (p < 0.001). Patients diagnosed ≤45 were 55.5% NSND, while older onset cases were 30% NSND (p < 0.001). In a multivariable logistic regression, OCSCC diagnosis ≤45 was associated with female patients (aOR=3.583, CI: 2.384, 5.386), Black patients (aOR=1.987, CI: 1.112, 3.548), and individuals with NSND status (aOR=1.572, CI: 1.155, 2.141). Oral tongue anatomic subsite was less common in patients diagnosed ≤45 (aOR=0.485, CI: 0.301, 0.843).

Conclusions: In this cohort, odds of early-onset rather than late-onset OCSCC were increased for female patients, Black patients, those without traditional risk factors, and those with non-oral tongue subsite. While prior population-level studies have emphasized the increasing incidence of OCSCC among white females, our findings suggest that Black individuals with OCSCC are more likely to present at a young age. The inverse association between tongue subsite and early-onset OCSCC contrasts with literature noting an increased proportion of tongue-site disease in early onset groups. Our findings highlight heterogeneity in early OCSCC that may inform future risk stratification and etiologic studies.