Prognostic and clinicopathological significance of cyclin D1 expression in oral squamous cell carcinoma: A systematic review and meta-analysis

Objectives: To evaluate the prognostic significance of cyclin D1 (CD1) overexpression in OSCC. Material and methods: We searched studies published before August 2017 (Pubmed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (Quality in Prognosis Studies [QUIPS] tool). The impact of CD1 overexpression on overall survival and disease-free survival, T status, N status, stage, and histological degree was meta-analyzed. We analyzed heterogeneity among studies, conducted sensitivity analyses, analyzed small-study effects, and conducted subgroup analyses. Results: 31 studies (2942 patients) met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that CD1 overexpression had a strong statistical association with worse overall survival (HR=2.00, 95% CI=1.59-2.51, p < 0.001), worse disease-free survival (HR=1.46, 95% CI=1.13-1.87, p=0.003), higher T status (OR=1.51, 95% CI=1.07-2.13, p=0.02), N+ status (OR=2.16, 95% CI=1.60-2.92, p < 0.001), advanced stage (OR=1.44, 95% CI=1.15-1.81, p=0.002), and high histological grade (OR=1.60, 95% CI=1.12-2.29, p=0.010). We observed heterogeneity in all parameters except for disease-free survival and clinical stage. We found effect of small studies on T and N status. The tonguel SCC subgroup showed the strongest association between CD1 overexpression and worse development. In addition, application of a cutoff point >= 10% tumor cells with nuclear CD1 expression maintained most of the significant associations reported. Conclusions: These findings indicate that immunohistochemical assessment of CD1 overexpression may be useful as a prognostic biomarker for OSCC.