Prognostic Value of Perineural Invasion in Oral Tongue Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

ObjectivesA significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell carcinoma (OTSCC), but some results remain conflicting. This study aimed to determine whether patients with OTSCC with PNI have a worse prognosis than those without PNI.Materials and MethodsPubMed, Embase, and the Cochrane Library were queried for potentially eligible articles published up to December 2020. The primary outcomes were the hazard ratio (HR) for locoregional recurrence, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). The random-effect model was used in all analyses.ResultsSeventeen studies (4445 patients) were included. Using adjusted HRs, the presence of PNI was associated with a higher risk of locoregional recurrence (HR=1.73, 95%CI: 1.07-2.79, P=0.025, I2 = 33.1%, Pheterogeneity=0.224), worse OS (HR=1.94, 95%CI: 1.39-2.72, P<0.001, I2 = 0.0%, Pheterogeneity=0.838), worse DFS (HR=2.13, 95%CI: 1.53-2.96, P<0.001, I2 = 48.4%, Pheterogeneity=0.071), and worse CSS (HR=1.93, 95%CI: 1.40-2.65, P<0.001, I2 = 25.5%, Pheterogeneity=0.251). PNI had an impact on locoregional recurrence in early-stage OTSCC but not in all stages, and on OS, DFS, and CSS in all-stage and early-stage OTSCC. The sensitivity analyses showed that the results were robust.ConclusionThe presence of PNI significantly affects the locoregional recurrence and survival outcomes among patients with OTSCC.

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

“…In such contextual disagreement, a meta-analysis is important to settle controversies arising from conflicting results due to its ability to disregard bias posed by individual studies. With a moderate to high quality of evidence, the results of this metaanalysis showed that the presence of PNI was strongly associated with increased risk of mortality and recurrence, confirming two previous meta-analyses on PNI (54,55). Although there are some overlap among the meta-analyses, the first included head and neck squamous cell carcinomas (54) and the second included only oral tongue carcinomas (55), whereas we performed our meta-analysis with studies that reported a Cox multivariateadjusted HR in oral cavity cancers, which brings refinement for the conclusion.…”

“…With a moderate to high quality of evidence, the results of this metaanalysis showed that the presence of PNI was strongly associated with increased risk of mortality and recurrence, confirming two previous meta-analyses on PNI (54,55). Although there are some overlap among the meta-analyses, the first included head and neck squamous cell carcinomas (54) and the second included only oral tongue carcinomas (55), whereas we performed our meta-analysis with studies that reported a Cox multivariateadjusted HR in oral cavity cancers, which brings refinement for the conclusion. Therefore, studies on PNI should focus on formulating a clear definition, considering an objective and more reproducible criteria for histopathologic assessment.…”

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][11][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.…”

Prognostic role of primary tumor metabolic-volumetric parameters of 18F-fluorodeoxyglucose positron emission tomography in tongue squamous cell carcinoma

“…Nevertheless, the prognosis of patients within the same TNM stage may vary (4). In addition to TNM staging system, various histopathological risk factors (depth of invasion, perineural invasion [PNI], surgical margin status, lymphovascular invasion [LVI],) in resectable TSCC can be used to predict patient prognosis (5)(6)(7)(8)(9). However, histopathological prognostic markers can only be obtained after surgical resection.…”