"A systematic literature review of the epidemiology, clinical, economic and humanistic burden in recurrent respiratory papillomatosis"

Abstract

Introduction: Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV), characterized by recurrent papillomas in the respiratory tract. Presenting as either juvenile-onset RRP (JoRRP) or adult-onset RRP (AoRRP), the severity of the disease is subjective and unpredictable. Lack of curative therapies necessitates disease management involving repeated surgical removal of lesions. The review aimed to assess the clinical, humanistic and economic burden associated with RRP.

Methods: Systematic literature reviews of Embase^®, MEDLINE^® and Cochrane databases were conducted for epidemiology, clinical, humanistic, and economic burden, from database inception to November 30, 2022. Conference abstracts were also searched (2019-2022). Key inclusion criteria consisted of juveniles or adults with RRP/laryngeal papillomatosis, with no restriction on study country, interventions, or comparators. Outcomes of interest included incidence, prevalence, risk factors, symptomatic presentation, HPV genotype, cost burden, resource use and health related quality of life (HRQoL).

Results: In JoRRP, the incidence rate ranged from 0.2-2.1 per 100,000 and the prevalence rate ranged from 0.8-4.3 per 100,000. Incidence and prevalence of AoRRP were 0.2-3.9 and 0.4-8.4 per 100,000, respectively. Limited studies reported the subsequent impact of introducing national prophylactic HPV immunisation programs on JoRRP epidemiology, but where available, they were associated with significantly reduced incidence rates. Symptomatic presentations were diverse, with voice impact and breathing difficulties commonly reported. More aggressive disease was linked to earlier age of onset and HPV11 genotype. Healthcare utilisation was largely driven by surgical interventions, due to lack of curative treatments. Cost burden was substantial, with JoRRP associated with triple the costs of AoRRP in the US. Patients with JoRRP and AoRRP experienced considerable HRQoL impairment, particularly relating to voice disorder.

Conclusion: Extensive clinical, humanistic and economic disease burden was reported for both JoRRP and AoRRP, as it is a chronic condition, with propensity to recur and spread. Feasibility of improving HPV prophylactic vaccination coverage against HPV6/HPV11 should be explored to reduce incidence, alongside efforts to improve treatment of JoRRP and AoRRP patients. Despite the existing literature, RRP remains a poorly understood disease, and future research on risk factors and medical options are needed.

Keywords: AoRRP; Clinical burden; Economic burden; Epidemiology; Health related quality of life (HRQoL); Human papillomavirus (HPV); Humanistic burden; JoRRP; Recurrent respiratory papillomatosis (RRP); Treatment patterns.