The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

Abstract

ObjectiveOver many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.MethodsA systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.ResultsThe study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.ConclusionOur results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.

Emerging histopathologic markers in early‐stage oral tongue cancer: A systematic review and meta‐analysis

“…Histological characteristics of the tumor and its surrounding tissues play an important role in the diagnosis of tumor biopsies, and are becoming increasingly important in prognostication. Such features include depth of invasion and perineural invasion, which are currently included in the pathology report 10 and have been recently reviewed in studies of heterogenous subsites of oral squamous cell carcinoma 10–12 . Furthermore, many HE‐related prognostic markers have been introduced in recent studies.…”

“…Such features include depth of invasion and perineural invasion, which are currently included in the pathology report 10 and have been recently reviewed in studies of heterogenous subsites of oral squamous cell carcinoma. [10][11][12] Furthermore, many HE-related prognostic markers have been introduced in recent studies. Although these have shown good prognostic value for early-stage OTSCC, they are not included in clinical implementation.…”

Surgical tumour margins and their significance in oral squamous cell carcinoma

“…A recent meta-analysis, the largest of its kind to date, has found a strong association between the positive tumour margin and the risk of overall survival (OS), disease-specific survival (DSS) and recurrence. 10 50 eligible studies with pooled analyses of surgical margins were considered. These included 63 470 patients (31 studies), with OS data, 20 680 patients 19studies with DSS data and 15 300 patients (25 articles) with data for disease-free survival (DFS).…”

“…Most published studies have compared clear margins (>5 mm of normal tissue) against a combination of close (1–4 mm of normal tissue) and involved (<1 mm of normal tissue) margins. In the recent large meta‐analysis, 10 20 studies did not define the margin distance but instead grouped tumour resections as those with either clear margins or close/involved margins. Pooled analyses confirmed that one or more involved resection margins were significantly associated with worse OS, DSS and DFS, irrespective of the amount of normal tissue from the tumour edge in the rest of the specimen 10 …”

“…Pooled analyses confirmed that one or more involved resection margins were significantly associated with worse OS, DSS and DFS, irrespective of the amount of normal tissue from the tumour edge in the rest of the specimen. 10…”