Dolens Eder da Silva, Dourado Mauricio Rocha, Almangush Alhadi, Salo Tuula A, Gurgel Rocha Clarissa Araujo, da Silva Sabrina Daniela, Brennan Peter A, Coletta Ricardo D
Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, Brazil.
University of Western São Paulo (UNOESTE), Presidente Prudente, Brazil.
Front Oncol. 2021 Nov 10;11:784924. doi: 10.3389/fonc.2021.784924. eCollection 2021.
Over 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.
A 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.
The 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.
Our 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.
International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.
几十年来，关于组织病理学特征的研究不仅为口腔鳞状细胞癌（OSCC）的治疗方向和预后提供了高水平的证据，也存在不一致之处，给临床应用带来困难。OSCC的第8版TNM分期系统已经认识到一些组织病理学特征的重要性，将浸润深度（DOI）纳入T分类，将结外扩展（ENE）纳入N分类。本系统评价及荟萃分析的目的是确定OSCC风险评估和治疗计划中最具临床相关性的组织病理学特征，并阐明文献中的差距。
按照PRISMA指南进行系统评价，纳入标准基于人群、暴露因素、对照、结局和研究类型（PECOS）。在PubMed、Cochrane、Scopus和Web of Science中检索探索组织病理学特征对OSCC结局影响并采用Cox多变量分析的文章。汇总数据采用随机效应或固定效应模型的逆方差法进行分析，采用预后研究质量（QUIPS）评估偏倚风险。采用推荐分级的评估、制定和评价（GRADE）标准评估证据质量。
该研究纳入了1999年至2021年发表的172篇文章。荟萃分析证实了DOI、ENE、神经周围浸润、脉管浸润和手术切缘受累的预后潜力，并为骨浸润、肿瘤厚度和浸润模式与不良生存风险增加之间的关联带来了有前景的结果。尽管研究数量较少，结果也显示肿瘤芽生和肿瘤-间质比在预测OSCC患者生存方面具有临床意义。大多数研究被认为偏倚风险低或中等，证据的确定性从极低到高不等。
我们的结果证实了许多组织病理学特征潜在的预后价值，并突出了其他特征的有前景的结果；然而，建议进一步研究采用一致的设计，填补OSCC预后组织病理学标志物相关性方面的文献空白。
国际前瞻性系统评价注册库（PROSPERO），标识符CRD42020219630。
