| Objectives1. To evaluate the efficacy of MMR vaccine in the treatment of juvenile-onset recurrent respiratory papillomatosis as adjuvant therapy by clinical and experiment researches, and analyze the distribution of HPV type and its relation with the severity of the disease.2. To assess the efficacy of cidofovir on recurrent respiratory papillomatosis by Meta-analysis.Methods1. Thirty-one children with RRP aged1-15were enrolled between January2010and December2011in Eye and ENT Hospital of Fudan University, which were assigned randomly to intervention group or control group. Fifteen subjects in intervention group were treated with local application MMR vaccine on the lesion after surgery; sixteen subjects in the control group were treated with surgical excision alone. The staging assessment sheet for RRP was used on every patient. The relapse time, initial and final staging scores and the amount of affected sites were compared between two groups using Cox regression model of multivariate analysis, paired-samples T testing or independent-samples T testing by the SPSS17.0software.2. Thirty-three laryngeal specimens of patients with JORRP, including twenty-five patients enrolled in clinical trail and eight patients out of trial, were taken and detected HPV genotype using DNA hybridization technique. The quantity of virus of positive specimens was measured by fluorescence quantitative polymerase chain reaction. The relation between HPV genotype and severity of RRP was analyzed in six aspects:onset age, the total number of surgery and surgery times per year, tracheotomy, Derkay scores, affected sites, and viral load. The differences of distribution of HPV genotype and viral load between two groups were evaluated. All the statistical analyses were performed using paired-samples T testing, independent-samples T testing or nonparametric two independent-samples Wilcoxon rank-sum testing by the SPSS17.0software.3. Clinical controlled trials which assessed the efficacy of cidofovir in the treatment of recurrent respiratory papillomatosis were searched through Pubmed, EMBASE, Web of science datebase, Cochrane library, CNKI and Weipu Chinense Journal Database. After screening literatures using inclusion and exclusion criteria and performing quality assessment, related data were extracted from included literatures. The efficacy of cidofovir was Meta analyzed using random effects models, and verified the results by sensitivity analysis and funnel plot. All the statistical analyses were performed using Review Manage4.2software.Results1. Before the comparison between the intervention group and control group, seven patients aged more than ten or performed tracheotomy and one patient lost to follow-up were excluded. Twenty-three patients were analyzed. The remission time of control group had extended90.08days compared with intervention group, the interval between operations of intervention group had extended27.01days compared with control group; scores and the number of affected sites of two groups were decreased, but there were no significant difference between two groups. Multivariate analysis showed that there was significant relevance between scores and relapse time(P=0.031), but the age and group were not significantly relevant with relapse time. In addition, among the patients aged more than ten or performed tracheotomy, their severity of disease and the number of affected sites in intervention group were decreased, while those of control group were increased. No patient showed drug-related adverse effect.2. All the specimens of JORRP were tested positive for HPV-6or HPV-11, and the main genotype was HPV-11(72.7%). No significant difference of the onset age, total number of surgery and surgery times per year, tracheotomy, Derkay scores, affected sites and viral load was found between HPV-6group and HPV-11group. After treatment with MMR vaccine, viral load of intervention group was (9.56±11.03)×108copies per milliliter, that of control group was (22.01±17.78)×108copies per milliliter, there was significant difference between two groups(P=0.040).3. Three clinical controlled trials were included in the Meta analysis, which were retrospective studies and the data were from published English literatures. No significant difference of remission rate was found between the cidofovir group and control group(Total RR=0.79, Z=0.91, P>0.05). The result of sensitivity analysis(Total RR=0.76, Z=1.84, P>0.05) coincided with the Meta analysis, and funnel plot indicated the figure was asymmetry.Conclusions1. Compared with surgical excision alone, local application MMR vaccine as adjuvant therapy shows some benefit in treating recurrent respiratory papillomatosis to a certain degree. It may extend the interval between operations and decrease the severity of disease and the amount of affected sites, but the curative effect needs further confirmation. 2. The pathogen that causes JORRP is HPV-6or HPV-11, and the most of them is HPV-11(72.7%). There is no relation between HPV type and severity of JORRP, but the results show that MMR vaccine can reduce HPV viral load significantly. It is suggested that the MMR vaccine may inhibit replication of HPV DNA.3. Based on the present research, there is no sufficient evidence suggested that cidofovir has alleviating effect on recurrent respiratory papillomatosis. The result is reliable due to sensitivity analysis, but there are many factors that may influence the results, further multicentre, large sample and high quality cilinical reasearch is needed to confirm the efficacy of cidofovir in the treatment of recurrent respiratory papillomatosis. |
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