Prognostic factors in young patients with oral cavity cancer: a systematic review and meta-analysis of 24 studies

TL;DR

This study reviews 24 studies to identify factors affecting survival in young oral cancer patients, finding that tumor size, nodal involvement, and tumor grade are key predictors.

Contribution

The study systematically identifies and quantifies prognostic factors specific to young-onset oral cancer patients through a meta-analysis of 24 studies.

Findings

Nodal involvement, high-grade tumors, and larger tumor size are strongly associated with poorer survival in young oral cancer patients.

Black race and poorly differentiated histology are also linked to worse outcomes.

Molecular and treatment-related factors show possible associations but require further validation.

Abstract

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.

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.

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.

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.

Figures