Overexpression of Hypoxia-Inducible Factor-1α Is a Predictor of Poor Prognosis in Cervical Cancer A Clinicopathologic Study and a Meta-analysis

Background Published data on the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in cervical cancer are conflicting and heterogeneous. We aimed to derive a more precise estimation of them. Methods We conducted a clinicopathologic study in 74 patients with early-stage cervical cancer treated through surgery and performed a meta-analysis among patients with cervical cancer of all stages to estimate the prognostic importance of HIF-1 expression for disease-free survival (DFS) and overall survival (OS). Expression of HIF-1 was evaluated through immunohistochemistry. Results A positive nuclear expression of HIF-1 was found in 94.6% of all specimens. There were significant associations between HIF-1 expression and International Federation of Gynecology and Obstetrics stage (P = 0.024), tumor size (P = 0.003), and anemia (P = 0.010), respectively. Log-rank tests revealed significant correlations between HIF-1 expression, International Federation of Gynecology and Obstetrics stages, tumor grade, tumor size and DFS/OS, respectively. The multivariate Cox regression analyses revealed HIF-1 overexpression and high tumor grade to be independent predictors for impaired DFS (HIF-1 overexpression: hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.10-6.47; high tumor grade: HR, 5.56; 95% CI, 1.47-21.13) and OS (HIF-1 overexpression: HR, 2.57; 95% CI, 1.06-6.23; high tumor grade: HR, 6.23; 95% CI, 1.49-25.97). The results of 10 studies indicated that HIF-1 overexpression predicted poor DFS (HR, 1.98; 95% CI, 1.22-3.21) and OS (HR, 2.58; 95% CI, 1.86-3.56) for cervical cancer. Conclusions The present clinicopathologic study and meta-analysis showed that HIF-1 overexpression is associated with poor survival of cervical cancer and emphasized the importance of HIF-1 alpha as a predictor for cervical cancer.