Recurrent respiratory papillomatosis (RRP) is a benign condition predominantly affecting the larynx and trachea (and occasionally bronchi and lung parenchyma). It is characterised by papillomatous (wart‐like) growths in the upper airway. These papillomata may cause life‐threatening airway obstruction or voice change (Derkay 2001). It is a potentially devastating disease with significant morbidity although it is rarely fatal. RRP has a bimodal age distribution, presenting commonly in children younger than five years or in adults between 20 and 30 years (Shykhon 2002). Yearly incidence has been reported as 4.3 per 100,000 in children and 1.8 per 100,000 in adults (Shykhon 2002).

The primary causative agent is Human Papilloma Virus (HPV) (Gissman 1982), a small, non‐enveloped, 20‐sided, capsid virus with double‐stranded circular DNA. The virus targets epithelial cells and can exist within its host in an active or latent form. HPV is the same virus associated with skin warts, genital condyloma, and cervical cancer. Although around 90 different types of HPV have been identified thus far (Menzo 2001), two types are thought to cause the majority of RRP, namely HPV‐6 and HPV‐11 (Corbitt 1988). Type 11 appears to be the more virulent of the two types, associated with earlier presentation, longer disease activity, more surgical procedures, higher mortality rate, and more frequent malignant transformation (Rabah 2001). Co‐infection of HPV with other viruses has been demonstrated (including Herpes Simplex virus, Cytomegalovirus, and Epstein‐Barr virus) and this can be predictive of an aggressive clinical course (Pou 1995). In juvenile‐onset RRP, transmission is usually secondary to direct contact with papillomata in an infected birth canal from maternal cervical HPV infection (Dillner 1999; Silverberg 2003). In the case of adult‐onset RRP, modes of disease transmission have not been well established. Postulated mechanisms include activation of a latent virus present since birth, or infection acquired in adolescence or adult life as a result of oral or sexual contact (Kashima 1992).

The common symptoms of RRP include progressive hoarseness, stridor and respiratory distress. Less commonly RRP can present with a chronic cough, recurrent pneumonia, failure to thrive, dyspnoea and dysphagia (Derkay 2001). Diagnosis is made by visualisation with flexible nasolaryngoscopy or direct laryngo‐bronchoscopy. Biopsy of the lesions is useful for histologic confirmation of respiratory papillomatosis and to exclude malignant transformation. Derkay and Coltrera have established a staging system based upon area of involvement, severity of involvement, and observational data such as the patient's voice quality and/or extent of respiratory distress (Derkay 1998). Inter‐observer reliability has now been demonstrated for this staging system (Hester 2003). The primary purpose of this system is to standardise the evaluation of RRP patients so that established and emerging treatments can be evaluated.

The goals of therapy are to relieve airway obstruction, improve voice quality, and facilitate remission. Treatment usually involves repeated surgical debulking of the papillomata under a general anaesthetic. Paediatric patients can need several procedures over many years. Several agents have been proposed as adjuvants to surgical debulking. These include antiviral agents, alpha‐interferon, indole 3‐carbinol, and photodynamic therapy. A variety of antiviral therapies have been used to treat RRP. These include systemically administered agents such as aciclovir (formerly called acyclovir) and ribavirin, and others injected into the lesions such as cidofovir. The mechanism of action of antiviral compounds is predominantly inhibition of viral nucleic acid synthesis. Direct action against the viruses involved in RRP is the likely mechanism for antiviral therapy efficacy. Various side effects have been associated with the use of available antiviral agents. These have included nausea, vomiting, abdominal pain, acute renal impairment, hepatitis, and neutropenia (BNF 2003).

There have been no systematic reviews of the effectiveness and safety of using antivirals as adjuvant therapy in the treatment of RRP. Although an uncommon condition, RRP carries significant morbidity, and any medical therapy that has proven benefits could be usefully applied to this population. This review sets out to consider the current evidence for using antivirals in RRP.