Objectives To perform systematic review and meta‐analysis on correlations between cancer‐associated fibroblasts (CAFs) and the risk of death for patients with oral squamous cell carcinoma. Subjects and methods English literature (1966–2018) was systematically analyzed for studies that immunohistochemically assessed CAF density by alpha‐smooth muscle actin and presented 5 year survival rates by Kaplan–Meier plots. Mean age of patients, proportion of male/female patients, and male/female majority (>50% male/female patients) per study were also collected. Significance level for statistical models was p < 0.05. Results Meta‐analysis comprised 11 studies/1,040 patients. Univariate Cox regressions showed that high CAF density was a negative prognostic factor in studies with female and male majority [OR 5.329 (95% CI 3.223–8.811), p < 0.001, and OR 2.208 (95% CI 1.717–2.839), p < 0.001, respectively]. High CAF density with male majority was associated with a more favorable prognosis [OR 0.996 (95% CI 0.979–1.013), p < 0.001]. Multivariate Cox regressions showed that death risk was significantly higher among patients with high CAF density compared to low CAF [OR 2.741 (95% CI 2.220–3.384) p < 0.001]. High mean age and male proportion were significantly protective [OR 0.940 (95% CI 0.925–9.955), p < 0.001, OR 0.125 (95% CI 0.018–0.867), p = 0.035), respectively]. Conclusions CAFs increased death risk, male majority, and higher mean age were protective. A clinically validated cutoff for CAF density could serve as a reliable prognostic tool.

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