Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection: A systematic review and meta-analysis of randomized clinical trials

Abstract

Background: We sought to conduct a systemic review and meta-analysis of randomized clinical trials to assess the efficacy and safety of photodynamic therapy (PDT) in cervical intraepithelial neoplasia (CIN) and cervical human papilloma virus (HPV) infection.

Methods: The Medline, EMBASE, and Cochrane Central Register databases were searched using relevant keywords for entries up to May 1, 2017, irrespective of year of publication. The language was restricted to English. Randomized clinical trials and qualitative studies comparing PDT and placebo for CIN or HPV-positive patients were included. We assessed the evidence quality using a risk of bias graph in RevMan V5.3 and the Grading of Recommendations Assessment, Development, and Evaluation scoring system.

Results: Of the 168 studies identified, only 4 RCTs met the inclusion criteria for meta-analysis. In all, 292 and 141 patients received PDT or placebo, respectively. PDT significantly increased the complete remission rate (CRR) among those with CIN (odds ratio [OR]: 2.51 [1.23-5.12]; P = .01) and HPV infection (OR: 3.82 [1.91-7.65]; P = .0002). The adverse events rate (AER) for PDT was greater than that for placebo (OR: 13.32 [4.44, 40.02]; P < .00001). The overall evidence quality was very low. Similarly, in a systematic review including 21 qualitative records, the CRRs for CIN patients with PDT and cervical HPV infection patients with PDT were 82.0% and 77.5%, respectively. The AER for PDT was 31.6%, which was lower than that observed in our meta-analysis (74.6%).

Conclusions: PDT that targets CIN or cervical HPV infection improves the CRR, but slightly compromises safety. Further studies are necessary to identify the most effective and least toxic photosensitizer.

Figure 1

Risk of bias. We evaluated the risk of bias by using RevMan V5.3. A, Risk of bias for individual studies determined using the Cochrane tool for assessment of risk of bias. B, Risk of bias graph: summary of risk of bias is presented as percentage across all included studies.

Figure 2

GRADE scores. Three reviewers evaluated the quality of the studies with GRADE profiler 3.6.1 to assess evidence quality. A, GRADE score for CRR of CIN with PDT. B, GRADE score for CRR of cervical HPV infection with PDT. C, GRADE score for AER of CIN or cervical HPV infection with PDT.

Figure 3

Forest plot of comparison of RCTs: CRR in CIN patients receiving PDT vs. patients receiving placebo. We used RevMan V5.3 for data processing. The data were analyzed by using the Mantel–Haenszel method and random effects model and presented as odds ratio (OR) with 95% confidence interval (CI). I² = 0 implies that there was no heterogeneity, P < .05 indicates statistical significance.

Figure 4

Forest plot of comparison of RCTs: CRR in cervical HPV infection patients receiving PDT vs. patients receiving placebo. Data processing was performed using RevMan V5.3. The data were analyzed by Mantel–Haenszel method and random effect model and presented as odds ratio (OR) with 95% confidence interval (CI). I² = 0 indicates the absence of heterogeneity, P < .05 indicates statistical significance.

Figure 5

Forest plot of comparison of RCTs: AER in patients receiving PDT vs. patients receiving placebo. We performed data processing through RevMan V5.3. Data were analyzed by Mantel-Haenszel method and random effects model and presented as odds ratio (OR) with 95% confidence interval (CI). I² = 0 indicates the absence of heterogeneity, P < .05 indicates statistical significance.