Prognostic biomarkers in oral cancer: a systematic review

Over the years, several tumor biomarkers have been suggested to foresee the prognosis of oral squamous cell carcinoma (OSCC) patients. Here, we present a systematic review to identify, evaluate and summarize the evidence for OSCC reported markers. Eligible studies were identified through a literature search of MEDLINE/PubMed until January 2016. We included primary articles reporting overall survival, disease-free survival and cause-specific survival as outcomes. Our findings were analysed using REporting recommendations for tumor MARKer prognostic studies (REMARK), QuickGo tool and SciCurve trends. We found 41 biomarkers, mostly proteins evaluated by immunohistochemistry. The selected studies are of good quality, although, any study referred to a sample size determination. Considering the lack of follow-up studies, the molecules are still potential biomarkers. Further research is required to validate these biomarkers in welldesigned clinical cohort-based studies.


César Rivera, Ana Karina de Oliveira, Rute Alves Pereira e Costa, Tatiane De Rossi and Adriana Franco Paes Leme.

Research highlights

  • Systematic review performed to identify published prognostic OSCC biomarkers.
  • Evaluation of oral cancer biomarkers related to clinical outcomes as: overall survival, disease-free survival or cause-specific survival.
  • Forty-one potential biomarkers are awaiting for validation in cohort-based studies.
Prognostic biomarkers in oral cancer

Figure 1. Prognostic biomarkers in oral cancer: a systematic review.


Mouth neoplasms; oral cancer; oral squamous cell carcinoma; biomarkers, tumor; review, systematic.

Research conclusion

Recent research in OSCC has identified a multitude of potential markers that have a significant role in prognosis. In this systematic review, despite the inherent limitations, we identified several potential biomarkers of particular interest that appear to carry prognostic significance. Considering the validation step as a process of assessing the biomarker and its measurement performance characteristics, and determine the range of conditions under which
this biomarker can provide reproducible data1
, our results show biomarkers in the discovery phase, thereby leading us to call them OSCC ‘‘potential biomarkers”. Nevertheless, it is urgent to apply validation methods to provide clinically useful oral cancer biomarkers.

Full access at 

Prognostic biomarkers in oral squamous cell carcinoma: A systematic review
Rivera, César et al. Oral Oncology , Volume 72 , 38 – 47. Link:


J. Hunter D, Losina E, Guermazi A, Burstein D, N. Lassere M, Kraus V. A Pathway and Approach to Biomarker Validation and Qualification for Osteoarthritis Clinical Trials. Current Drug Targets. 2010;11(5):536-545. doi: 10.2174/138945010791011947 [Source]
Rivera C, Oliveira AK, Costa RAP, De Rossi T, Paes Leme AF. Prognostic biomarkers in oral squamous cell carcinoma: A systematic review. Oral Oncology. 2017;72:38-47. doi: 10.1016/j.oraloncology.2017.07.003 [Source]
Prognostic biomarkers in oral cancer: a systematic review
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