Clinicopathological significance of survivin expression in patients with cervical cancer: A systematic meta-analysis

Abstract

Background: Survivin has been shown to play an important role in cancer pathogenesis. However, its role in cervical cancer development is still controversial. This study was performed to evaluate the clinical significance of survivin expression in cervical cancer.

Methods: Search of some online electronic databases was conducted to identify available studies. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were calculated and analyzed.

Results: Finally, 18 eligible studies with 791 cervical cancer patients, 1,013 cervical intraepithelial neoplasia (CIN) lesions, 199 normal cervical tissues, and 95 samples with chronic cervicitis were identified in this analysis. The pooled OR of survivin expression was found to be significantly higher in the samples from cervical cancer than in those from CIN lesions, normal cervical tissues, and chronic cervicitis. When cervical cancer was compared to CIN lesions, the subgroup analysis by ethnicity showed that survivin expression was associated with a risk of cervical cancer in Asians (P < 0.001), but not in Caucasians (P = 0.659). In addition, survivin was significantly more overexpressed in high-grade cervical cancer than in low-grade cervical cancer. Its expression was also more elevated in advanced-stage patients than in early-stage patients, in lymph node metastasis than in lymph node without metastasis, and in squamous cell carcinoma (SCC) than in adenocarcinoma (AC).

Conclusions: The expression of survivin may play a key role in the carcinogenesis, progression, and metastasis of cervical cancer. However, survivin expression may be involved in the progression of CIN lesions only in the Asian population. Survivin expression is associated with an increased risk of SCC. Additional studies with larger sample sizes are needed in the future to confirm our findings.

Keywords: CIN lesions; cervical cancer; clinicopathological features; expression; survivin protein.

Figure 1.

Flow chart of the literature search strategy for eligible studies.

Figure 2.

Forest plot of the correlation between survivin expression and cervical cancer in 16 studies with 732 cervical cancer patients and 1,013 CIN lesions: OR = 3.01, 95% CI = 1.60–5.68, P = 0.001, 13 studies with 664 patients with cervical cancer and 199 normal cervical tissues: OR = 51.72, 95% CI = 22.83–117.20, P < 0.001, 5 studies with 210 cervical cancer patients and 95 samples with chronic cervicitis: OR = 26.55, 95% CI = 7.20–97.95, P < 0.001.

Figure 3.

Forest plot of the correlation between survivin expression and tumor grade in 8 studies including 106 high-grade patients with cervical cancer and 307 low-grade patients with cervical cancer: OR = 2.13, 95% CI = 1.13–3.98, P = 0.019.

Figure 4.

Forest plot of the correlation between survivin expression and clinical stage in 8 studies including 122 advanced-stage patients with cervical cancer and 287 early-stage patients with cervical cancer: OR = 2.96, 95% CI = 1.51–5.80, P = 0.002.

Figure 5.

Forest plot of the association between survivin expression and histological subtype in 7 studies involving 302 squamous cell carcinoma (SCC) and 55 adenocarcinoma (AC) patients: OR = 1.99, 95% CI = 1.02–3.88, P = 0.045.

Figure 6.

Forest plot of the association between survivin expression and lymph node status, 7 studies involving 200 lymph node positive patients with cervical cancer and 201 lymph node negative patients with cervical cancer: OR = 8.20, 95% CI = 4.09–16.45, P < 0.001.

Figure 7.

Forest plot of the associations based on sensitivity analyses in cancer vs. CIN lesions and chronic cervicitis, cancer vs. CIN lesions: OR = 5.94, 95% CI: 4.30–8.19, P < 0.001, I² = 19.4%; cancer vs. chronic cervicitis: OR = 13.79, 95% CI: 6.26–30.34, P < 0.001, I² = 0.0%.