Squamous cell carcinoma associated with intralesional injection of cidofovir for recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis is a common neoplasm of the larynx that may lead to severe, recurrent lesions. Intralesional injection of cidofovir has shown promise as an adjuvant therapy. There is concern for possible malignant transformation with its use but, to our knowledge, this has not been documented in the literature. We report a case of invasive squamous cell cancer arising from squamous papilloma in a patient treated with multiple injections of cidofovir. Although causation is not shown, we believe the association presented is a valuable addition to the literature and an important consideration in the use of cidofovir. Laryngoscope, 119:567–570, 2009     

Long-term follow-up of pediatric recurrent respiratory papillomatosis managed with intralesional cidofovir

OBJECTIVE: Cidofovir is an acyclic nucleotide phosphonate antiviral medication that has been used intralesionally for the treatment of severe respiratory papillomatosis (RRP) in pediatric patients. The long-term efficacy of this medication was assessed in 11 children with severe RRP who previously required operative debulking every 2 to 6 weeks to maintain airway patency. STUDY DESIGN: Clinical case series. RESULTS: Ten of these children have completed therapy. Five are disease free over a mean follow-up period of 51.6 months. Five other patients with active RRP decreased their mean severity scores from 17.8 (range 11-26) to 4.0 (range 2-6) and no longer require cidofovir. One patient continues to receive cidofovir for recurrent disease after an initial favorable response. Throughout the 6-year observational period, no patients demonstrated any adverse effects, laboratory abnormalities, or evidence of carcinogenesis. CONCLUSION: Intralesional cidofovir is a useful adjunct for managing children with tenuous airways caused by previously uncontrolled papilloma.     

Safety of paediatric day-stay laryngeal surgery for recurrent respiratory papillomatosis

ObjectivesSafety assessment of day-stay laryngeal surgery in a cohort of children with recurrent respiratory papillomatosis (RRP). Recurrent respiratory papillomatosis is a chronic debilitating disease which usually requires multiple recurrent interventions under general anaesthesia. Day-stay surgery is an attractive option as it allows avoiding the inconvenience and costs of routine overnight admissions while recovering in the safe environment of the family home. This is the first study to assess the safety of day-stay laryngeal surgery in this cohort of patients.MethodsRetrospective cohort study of all consecutive RRP procedures performed between December 1998 and May 2015 in a single paediatric tertiary-level hospital.ResultsA total of 465 surgical procedures were performed in 20 patients. Average age on diagnosis was 4.5 years. 415 (89.25%) of the procedures were done as day cases without overnight admission. Average number of procedures per patient was 20 and 25 for Children positive to HPV6 and HPV11, respectively. Only one patient after one single procedure (presenting 0.21% of total procedures, 0.24% of day-stay procedures) represented after discharge.ConclusionsDay-stay surgery for children with RRP has a favourable safety profile in selected cases.     

Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) is a chronic and difficult to treat disease of the larynx. In 1998, the first article was published that described the use of the antiviral substance cidofovir to treat this disease. Although the results are promising, there remains some concern about the potential carcinogenicity of cidofovir. There is a demand for a qualitative review of the side-effects of this medicine. In this review, the side-effects of cidofovir are investigated. Special attention was given to the potential carcinogenicity of cidofovir. For this review a search is performed in PubMed and EMBASE for relevant articles in which the use of intralesional cidofovir for patients with RRP is described. Eventually, 31 articles could be included for this review. In these articles a total of 188 patients with RRP were described who underwent therapy with intralesional cidofovir. Five of these patients have developed dysplasia of the larynx during the treatment with cidofovir. This is a percentage of 2.7. This percentage is concurrent with the incidence of spontaneous malignant degeneration of RRP (2-3%). Based on this review, it can be concluded that the use of intralesional cidofovir does not increase the risk of laryngeal dysplasia. Apart from the articles that describe the intralesional administration of cidofovir, some articles have been published in which the use of intravenous cidofovir is described as a therapy for RRP. Therefore, a summary is given on the side-effects of intralesional cidofovir as well as a summary on the reported side-effects of the intravenous administration of cidofovir. Based on the outcomes of this review, recommendations are given for a safe use of cidofovir for treatment of recurrent respiratory papillomatosis in the future.     

Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: A systematic review

Objectives

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare yet aggressive disease caused by human papillomavirus (HPV). Although many newborns are likely exposed to HPV, few develop JoRRP and the clinical course of the disease varies from one child to another. This systematic review seeks to provide an up-to-date understanding of the risk factors for acquisition and severity.

Methods

We conducted a comprehensive literature search in EMBASE, MEDLINE and EBMR databases using various combinations of keywords related to JoRRP etiology, risk factors and severity. We also searched Google Scholar and the reference lists of eligible studies. Our search was limited to original studies published in French or English between 1995 and July 2012 and to patients under 20 years of age.

Results

Of 1362 citations, we retrieved 102 articles and found 14 additional studies. We retained 32 studies meeting inclusion criteria. All were observational and together included 2296 JoRRP cases. Risk factors could be classified mainly as maternal and birth history, viral genotype, and host factors. A history of genital warts during pregnancy and delivery was strongly linked to the development of JoRRP. Depending on ethnicity, specific human leukocyte antigen class II alleles and immune response factors were important determinants of JoRRP acquisition and severity. HPV-11 genotype and younger age at onset of JoRRP were important predictors of severity.

Conclusions

Genetic and immunological profiles underlying the acquisition and clinical course are not readily modifiable. Thus, preventing condylomas in women of childbearing age could reduce the burden of this life-threatening disease.     

CO2激光手术治疗复发性呼吸道乳头状瘤

复发性呼吸道乳头状瘤是呼吸道最常见的良性上皮性肿瘤,术后极易复发,频繁的手术干预,给患者及家属乃至整个社会带来了巨大的经济负担。目前手术仍为最主要的治疗方法,CO₂激光本身具有损伤小、术野出血少、精准度高、切割深度可控特点,有利于完整切除肿瘤;采取CO₂激光行黏膜下剥离实现完整切除复发性呼吸道乳头状瘤,其临床疗效显著,具有广阔的应用前景。     

Current advances in the basic research and clinical management of juvenile-onset recurrent respiratory papillomatosis

Juvenile-onset recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma viruses type 6 and 11 are important in the etiology of the papillomata and are most probably transmitted from mother to child during childbirth. Although spontaneous remission is frequent, a rare fatal course because of pulmonary spread or malignant transformation has occurred. CO₂ laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid α-interferon are the most common treatment modalities at present. However, several other treatment modalities have been tried with varying success. Recent advances in basic research and different therapeutic approaches are reviewed. Received: 13 October 1999 / Accepted: 3 December 1999     

Scientific and clinical aspects of the use of cidofovir in recurrent respiratory papillomatosis

OBJECTIVE: Cidofovir is the most contemporary adjuvant treatment for recurrent respiratory papillomatosis (RRP) and its use is increasing. Cidofovir is potentially harmful. Otolaryngologists should understand the science of cidofovir and review the current published data on the effects of this therapy. METHOD: Pubmed was searched using the terms cidofovir and papillomatosis. Comparisons were made between published articles. RESULTS: Thirteen articles were identified between 1998 and 2006, representing the treatment of 142 patients. Cidofovir did result in a significant improvement of papillomatous lesions in the majority (60%) of patients despite the use of different regimes of cidofovir administration. There was no unifying protocol in use. A partial response was demonstrated in 29% of patients. 7.5% had no response however, an additional 3.5% patients were lost to follow-up. No malignant change was reported. CONCLUSION: Cidofovir does appear to be effective in improving the outcome of patients with RRP. There are no reports of malignant transformation despite concerns raised by toxicology studies.