Proposed classification system for oral squamous cell carcinoma - "integrated histologic-molecular scoring system"...

Oral squamous cell carcinoma (OSCC) is a biologically heterogeneous disease with marked variability in clinical, radiographic, histological, and molecular behavior. Tumoral cellular differentiation and the degree of keratinization exhibited by the cells form the main criteria of the current histopathological grading system for OSCC. However, these provide a weak predictive value, because other histopathological characteristics utilized in other grading systems, such as invasion pattern, tumor budding, perineural and lymphovascular invasion, and tumor-stroma ratio have also been found to be independent predictors determining the diagnosis, as has tumoral behavior in a number of investigations over the last 10 years. This has been backed by the expression of certain molecular biomarkers, pertaining specifically to the lesion.

The proposed 'integrated histologic-molecular scoring system' (IHMSS) incorporates key histopathological parameters - including tumor differentiation, depth of invasion, pattern of invasion, lymphovascular invasion, perineural invasion, and tumor budding - alongside molecular and immunohistochemical markers implicated in OSCC pathogenesis, tumor progression, and invasiveness. Each parameter is assigned a weighted score based on biological relevance and evidence from existing literature. Cumulative scores are used to stratify tumors into distinct risk categories. The system is designed to be applicable to routine formalin-fixed paraffin-embedded tissue sections, and adaptable for both retrospective and prospective validation studies.

The total histologic invasion scores ranged from 4 to 7. Based on predefined cutoffs, 33.3% of cases were classified as low risk, while 50% were categorized as intermediate risk; no cases fell into the high-risk group. Tumor budding, pattern of invasion, and cancer-associated fibroblast (CAF) density were the primary contributors to score variability, whereas perineural and lymphovascular invasion were absent in all cases. Notably, well-differentiated tumors demonstrated variable risk stratification, highlighting the added value of composite scoring over conventional grading.

The IHMSS represents a novel, multidimensional classification approach that bridges histopathology and molecular oncology in OSCC. By incorporating tumor morphology and molecular alterations into a unified scoring model, the system addresses limitations of existing grading schemes and aligns with the principles of precision oncology. Validation through large-scale, multicentric studies is warranted to establish its prognostic and predictive utility.

The proposed IHMSS has the potential to enhance individualized risk assessment, guide treatment planning, and optimize follow-up strategies in patients with OSCC. Its application may aid clinicians in identifying biologically aggressive tumors at an early stage, thereby improving therapeutic decision making and patient outcomes.