Photodynamic therapy for recurrent respiratory papillomatosis

Background

Recurrent respiratory papillomatosis is a condition of the mucosal lining of the upper airway, which leads to multiple benign, wart-like growths (papilloma). Although not cancerous, it can lead to serious problems, including hoarseness and airway obstruction. The main treatment is repeated surgical removal of the papilloma using a laser or cutting instrument. However, multiple surgical procedures carry the risk of complications and can also result in long-term scarring. Photodynamic therapy works through the application of a light-sensitising substance, which is then activated by light of a specific wavelength. A chemical reaction creates powerful active molecules that destroy the papilloma locally. It can be used on its own or as an additional treatment together with surgical removal. It has been proposed that photodynamic therapy slows the growth of the papilloma and results in fewer recurrences and therefore fewer surgical procedures.

Study characteristics

We found one randomised controlled trial with a total of 23 participants for inclusion in this review. The study took place at two centres in the USA. Six of the 23 patients did not complete the study (dropped out). Participants who completed the study were outpatients, their age range was four to 60 years and 76% were men and 24% women. The study did not measure any of the outcomes important to patients (symptom improvement - respiratory distress/dyspnoea and voice quality, quality of life improvement and recurrence-free interval). It did measure the reduction in the volume of disease (assessed with an endoscope).

Key results

We found insufficient evidence from the included study that photodynamic therapy has a benefit on its own or in combination with surgery in recurrent respiratory papillomatosis. There was no clear evidence that effects observed in the treatment group were different to those in the control group. Adverse effects reported included airway swelling in a child with severe disease a few hours after photodynamic therapy, which required insertion of a breathing tube and a prolonged stay in hospital.

Quality of the evidence

The overall quality of the evidence is very low: there was no blinding of treatment and a high rate of drop-out. This evidence is up to date to January 2014.

Authors' conclusions: 

There is insufficient evidence from high-quality randomised controlled trials to determine whether photodynamic therapy alters the course of disease or provides an added benefit to surgery in patients with recurrent respiratory papillomatosis. Multicentre randomised controlled trials with appropriate sample sizes and long-term follow-up are required to evaluate whether photodynamic therapy is of benefit. Outcomes such as improvement in symptoms (respiratory function and voice quality) and quality of life should be measured in future trials.

Read the full abstract...
Background: 

Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP.

Objectives: 

To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults.

Search strategy: 

We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014.

Selection criteria: 

Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.  

Data collection and analysis: 

We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively.

Main results: 

We included one trial with a total of 23 participants. This study was at high risk of bias. None of our primary outcomes and only one of our secondary outcomes (reduction in volume of disease, assessed endoscopically) was measured in the study. There was no significant difference between the groups (very low-quality evidence). Adverse effects reported included airway swelling requiring intubation in a child with severe RRP a few hours after photodynamic therapy.

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