Prognostic Factors in Young Patients With Oral Cavity Cancer: A Systematic Review and Meta-analysis of 24 Studies

Rami Saade^1*Rita Khoury¹Jana Hassan²Gibran Atwi¹Hady Ghanem¹Caroline Jabbour¹Annoir Shayya¹

• ¹Lebanese American University Medical Center Rizk Hospital, Achrafieh, Lebanon
• ²Lebanese American University School of Medicine, Byblos, Lebanon

Background Young-onset oral cancer is increasingly recognized as a distinct clinical entity, yet prognostic determinants in this population remain poorly defined. This systematic review and meta-analysis aimed to identify and synthesize prognostic factors associated with overall survival among young patients with oral and tongue cancers. Methods A comprehensive search of PubMed, Scopus, and Web of Science was conducted on September 23, 2024. Eligible studies included observational cohorts reporting regression-derived prognostic estimates in young patients with oral cancer. Adjusted hazard ratios (aHRs) were pooled using random-effects models with restricted maximum likelihood, whereas unadjusted estimates were narratively summarized. Risk of bias was assessed using the NIH Quality Assessment Tool. Subgroup analyses were not feasible due to limited stratified reporting, and publication bias was not evaluated because all pooled analyses contained fewer than ten studies. Results Twenty-four studies encompassing 6,965 young patients were included. Several demographic factors showed no significant association with survival, including age and sex, while Black race was associated with worse outcomes (aHR = 2.79, 95% CI 1.40–5.56). Tumor characteristics linked to poorer prognosis included larger tumor size (aHR = 1.01 per cm, 95% CI 1.00–1.03) and greater depth of invasion (aHR = 1.03, 95% CI 1.01–1.05). High-grade tumors (grade 3–4) (aHR = 2.15, 95% CI 1.52–2.77) and poorly differentiated histology (aHR = 7.75, 95% CI 2.61–23.01) demonstrated strong adverse prognostic associations. Nodal disease significantly increased risk, including higher N stage (aHR = 1.24, 95% CI 1.11–1.37) and N+ status (aHR = 2.05, 95% CI 1.24– 2.85). Single-study findings—such as TERTp mutation (aHR = 3.00), PRKCA mutation (aHR = 3.57), Stage IVB, disease recurrence, and several treatment-related variables—suggest possible associations but remain inconclusive. Conclusions Among young patients with oral and tongue cancer, nodal involvement, high-grade or poorly differentiated tumors, increased depth of invasion, and larger tumor size were the most consistently associated with poorer survival. Evidence for molecular and treatment-related factors is limited and requires further validation. These findings highlight the need for standardized reporting and prospective studies tailored to young-onset disease.