University of Oulu

Dolens EdS, Dourado MR, Almangush A, Salo TA, Gurgel Rocha CA, da Silva SD, Brennan PA and Coletta RD (2021) The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis. Front. Oncol. 11:784924. doi: 10.3389/fonc.2021.784924

The impact of histopathological features on the prognosis of oral squamous cell carcinoma : a comprehensive review and meta-analysis

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Author: da Silva Dolens, Eder1,2; Dourado, Mauricio Rocha3; Almangush, Alhadi4,5;
Organizations: 1Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, Brazil
2University of Western São Paulo (UNOESTE), Presidente Prudente, Brazil
3Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil
4Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
5Department of Pathology, University of Helsinki, Helsinki, Finland
6Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
7Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil
8Department of Propaedeutics, School of Dentistry, Federal University of Bahia, Bahia, Brazil
9Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Faculty of Medicine, McGill University, Montreal, QC, Canada
10Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Department of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, QC, Canada
11Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, United Kingdom
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link:
Language: English
Published: Frontiers Media, 2021
Publish Date: 2021-12-17


Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.

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Series: Frontiers in oncology
ISSN: 2234-943X
ISSN-E: 2234-943X
ISSN-L: 2234-943X
Volume: 11
Article number: 784924
DOI: 10.3389/fonc.2021.784924
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3122 Cancers
Funding: This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2018/16077-6) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (407814/2018-3 and 303589/2019-1). MD was research fellow supported by FAPESP (2017/26764-8).
Copyright information: © 2021 Dolens, Dourado, Almangush, Salo, Gurgel Rocha, da Silva, Brennan and Coletta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.