Evaluation of Safety of Intralesional Cidofovir for Adjuvant Treatment of Recurrent Respiratory Papillomatosis

Abstract

ecurrent respiratory papillomatosis (RRP) is a disease characterized by benign papillomatous lesions of the upper airway that often cause debilitating dysphonia and may result in airway obstruction. Because of its recurrent nature, multiple surgical excisions are required to manage RRP, resulting in patient morbidity and high health care use. 1,2 Intralesional injections of the antiviral medication cidofovir have been used in an attempt to decrease the frequency of excisions and reduce the burden of disease for the patient 3,4 ; however, there have been concerns that cidofovir may produce adverse effects, including increased risk of malignant transformation. 5 Although several studies have found no increased risk of cancer in patients with RRP who are treated with cidofovir, [6][7][8][9][10][11] the safety profile of intralesional cidofovir injection in patients with RRP is not fully understood. Understanding the safety of intralesional cidofovir is essential for otolaryngologists treating patients with RRP with a high burden of disease who may be seeking adjuvant therapies. This study aims to provide further data on the safety of intralesional adjuvant cidofovir to inform physicians in their decision to offer this treatment to patients.Recurrent respiratory papillomatosis results from human papillomavirus infection, most commonly with subtypes 6 and 11. 12,13 Human papillomavirus is thought to infect the stem cells within the basal layer of the epithelium and either cause active disease or remain dormant. 14 The lesions of RRP IMPORTANCE The use of intralesional cidofovir injections for recurrent respiratory papillomatosis (RRP) remains controversial owing to concern regarding the risks of its use, including increased risk of dysplasia or carcinogenesis.OBJECTIVE To describe the rates of dysplasia, development of malignant lesions, and adverse events associated with use of intralesional cidofovir injections as adjuvant treatment for RRP compared with patients treated without adjuvant cidofovir. DESIGN, SETTING, AND PARTICIPANTSIn this case series performed at a tertiary care referral center, review of electronic medical records on all adult and pediatric patients (N = 154) treated for RRP with adequate follow-up from January 1, 2000, to December 31, 2016, was performed. Data were collected on the use of cidofovir, development and presence of dysplasia or malignant lesions, complications, and intersurgical interval.EXPOSURES Adjuvant intralesional cidofovir or surgical excision only. MAIN OUTCOMES AND MEASURESThe main outcomes measured were the development of dysplasia, malignant lesions, and complications from treatment. These outcomes were determined before collection of data. RESULTSOf the 154 patients included in the analysis, 83 patients (53.9%) received adjuvant intralesional cidofovir and 71 patients (46.1%) underwent surgical excision only. One hundred patients (64.9%) were male; mean age was 27.7 (95% CI, 24.3-31.2) years. Patients were followed up for a median (interquartile range) of 70 (24-118) mont...

Assessment of immunomodulation and regulation of cell cycle in epithelium and stroma after Cidofovir injection in patients with recurrent respiratory papillomatosis—Pilot study

“…The intraoperative supply of Cidofovir is a safe procedure as it is not associated with an increased risk of dysplasia or carcinoma or a statistically significant increase in complications 6 . Other side effects of Cidofovir treatment enlisted by Broekema and Dikkers 14 : cutaneous rash, headache, local inflammatory response, vocal cord scarring, compromised airway, disorders of hematologic, and chemical parameters in blood were not reported in our research group.…”

“…13 The intraoperative supply of Cidofovir is a safe procedure as it is not associated with an increased risk of dysplasia or carcinoma or a statistically significant increase in complications. 6 Other side effects…”

Intralesional cidofovir for the management of refractory cutaneous verrucae: a review of applications and opportunities

“… 25 However, a more recent study demonstrated that IL cidofovir use in patients with RRP did not increase rates of dysplasia or carcinoma development compared with control RRP patients. 26 …”

“…25 However, a more recent study demonstrated that IL cidofovir use in patients with RRP did not increase rates of dysplasia or carcinoma development compared with control RRP patients. 26 Large-scale studies addressing the need for laboratory monitoring of patients undergoing treatment with IL cidofovir are lacking. Regardless of administration route, one should consider close monitoring for possible nephrotoxicity through serum creatinine levels in patients who have preexisting renal dysfunction, require a large dose of cidofovir, or are on other medications that modify rates of renal excretion.…”

How Enhancing Immunity to Low‐Risk HPV Could Cure Recurrent Respiratory Papillomatosis

“…Use of adjuvant intralesional cidofovir remains controversial given the paucity of controlled clinical data yet continued widespread use. Continued use of cidofovir is supported by some retrospective studies suggesting a clinical benefit and evidence that there is little chance of harm with repeat administration 32 . Until more definitive and convincing clinical evidence emerges for other forms of adjuvant treatment for RRP, use of intralesional cidofovir will likely continue in select practices.…”