OBJECTIVE: The relationship between the worst pattern of invasion (WPOI) and the prognosis of oral squamous cell carcinoma (OSCC) remains controversial. This systematic review and meta-analysis was performed to determine the impact of the WPOI on the prognosis of OSCC.
METHODS: Studies from six databases were assessed for quality using the Newcastle-Ottawa Scale, and data were analyzed using Stata software.
RESULTS: Eighteen studies involving 3954 patients showed that patients with a WPOI of 4 to 5 had significantly worse overall survival, disease-specific survival, and disease-free survival than patients with a WPOI of 1 to 3. Significant associations of the WPOI with locoregional recurrence and mortality were found.
CONCLUSIONS: A higher WPOI was significantly associated with a worse prognosis of OSCC across various outcomes. Incorporating the WPOI into standard histopathological assessments may guide personalized treatments and improve outcomes.

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin-eosin-based histopathologic markers. Our meta-analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40-3.84; p < 0.01) and disease-specific survival (DSS) (1.89; 95% CI 1.13-3.15; p = 0.02). Worst pattern of invasion was associated with disease-free survival (DFS) (1.95; 95% CI 1.04-3.64; p = 0.04). Tumor-stroma ratio was also associated with DFS (1.75, 95% CI 1.24-2.48; p < 0.01) and DSS (1.69; 95% CI 1.19-2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor-stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost-effective and can be incorporated in daily practice.