Intralesional cidofovir vs. bevacizumab for recurrent respiratory papillomatosis: a systematic review and indirect meta-analysis

Background Specific HPV types cause recurrent respiratory papillomatosis (R.R.P.). When administered intralesionally, cidofovir, an antiviral agent, has shown favorable outcomes in reducing papilloma. Bevacizumab, an angiogenesis inhibitor, has demonstrated improved R.R.P. However, both treatments lack FDA approval for R.R.P. Our study aims to evaluate the efficacy and safety of intralesional Cidofovir and Bevacizumab for R.R.P. and compare the two interventions.Methods We searched five electronic databases to find relevant studies. After the screening, data were extracted from the included studies. Pooled ratios with 95% confidence intervals (CIs) were used for categorical outcomes, and mean difference (MD) was used for continuous outcomes. Statistical heterogeneity was evaluated using the chi-squared test for I2 statistics. The Cochrane Risk of Bias assessment tool was used to assess the methodological quality of randomized controlled trials (RCTs), while the National Institutes of Health's tool was used for observational studies. Analysis was done by Review Manager software.Results In our comprehensive meta-analysis of 35 articles involving 836 patients, cidofovir demonstrated an overall remission ratio of (0.90 [95% CI: 0.83, 0.98], p = 0.01), while bevacizumab (0.92 [95% CI: 0.79, 1.07]), p = 0.3). The complete remission ratio for cidofovir was (0.66 [95% CI: 0.57, 0.75], p > 0.0001), while bevacizumab was (0.29 [95% CI: 0.12, 0.71], p = 0.07). In partial remission, Bevacizumab showed a higher ratio than Cidofovir 0.74 [0.55, 0.99] vs. 0.40 [0.30, 0.54]. Bevacizumab had a pooled ratio of 0.07 [95% CI: 0.02, 0.30] in terms of no remission, indicating better outcomes compared to Cidofovir with a ratio of 0.28 [95% CI: 0.16, 0.51]. Additionally, Cidofovir showed a favorable decrease in the Derkay Severity Score (DSS) with a mean difference (MD) of 1.98 [95% CI: 1.44, 2.52].Conclusion Cidofovir had a higher impact on complete remission compared to Bevacizumab. Both showed partial remission, with Bevacizumab having a higher ratio. Moreover, Cidofovir showed a significant decrease in DSS. Bevacizumab had lower rates of no remission and recurrence and fewer adverse events compared to Cidofovir. However, the difference between the two treatments was not significant, except for partial remission.