Intralesional Cidofovir: A Systematic Review of Administration Protocols and Long-term Recurrence Rates in Adult and Juvenile Recurrent Respiratory Papillomatosis

Abstract

This is a systematic review aimed to explore Cidofovir administration protocols, recurrence rates, and long-term effectiveness for severe cases of recurrent respiratory papillomatosis (RRP). The primary goal was to identify current practices, determine the preferred protocol, and assess the adjuvant therapy's ability to prevent long-term papilloma recurrence in juvenile and adult-onset disease. The following databases were searched: Pubmed, Google Scholar (pages 1-10), EMBASE, Scopus, ISI (clarivate), Cochrane Library, and Journal Storage from 1996 to June 2022. Articles that reported the use of intralesional Cidofovir in RRP and reported remission/recurrence rates with follow-up were included in the review. The systematic review was registered through PROSPERO and contains the detailed protocol for the conduction of the review. A total of 389 records were identified, 126 titles and abstracts screened, 45 studies fully read, and 30 studies met the inclusion criteria. Two hundred and fourteen adult-onset RRP (AORRP) and 126 juvenile-onset RRP (JORRP) cases were treated with Cidofovir across the included studies. There was no universal protocol for administering Cidofovir, with variations in concentration, treatment period, number and interval of injections, and follow-up duration. Most lesions showed human papilloma virus types 6 and 11. Recurrence rates varied, and other outcomes reported included remission rates, lesion reduction, surgical intervals, and side effects. Some studies demonstrated significant improvements in disease severity and extended intervals between recurrences after Cidofovir administration. The analysis of 30 studies reveals the need for greater consistency in reporting treatment parameters and outcomes. The use of recurrence-free period as an outcome measure and the potential benefits of a concentration of 7.5mg/mL are identified. Additionally, the importance of viral typing within papilloma lesions is emphasized. To further enhance understanding and establish optimal protocols, future research should focus on uniform reporting, including severity, dosage, interval, treatment duration, functional outcome, and related procedures. PROSPERO CRD42022299549.