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

https://doi.org/10.1016/j.ijporl.2013.11.036Get rights and content

Abstract

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.

Introduction

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare yet aggressive disease caused by the human papillomavirus (HPV). The wart-like growths in the upper airway are mostly due to HPV genotypes 6 and 11 [1], [2]. Several observational studies have associated the JoRRP to maternal vaginal condylomas [3], [4], [5], [6].

The incidence and prevalence of JoRRP vary from one country to another. The incidence has been estimated at 0.24–4.3 per 100,000 children, the prevalence at 1.11–2.59 per 100,000 children [7], [8], [9], [10]. Although the disease is rare, morbidity is notoriously high. Recurrent proliferative lesions in the respiratory tract can spread to the trachea, bronchi or pulmonary parenchyma and compromise local function such as vocalization, breathing and swallowing [11], [12], [13], [14], [15].

The course of the disease can vary from mild to severe. Some children experience minor symptoms with spontaneous and complete remission at puberty, while others require multiple surgeries throughout childhood [13] at great physical, emotional, and financial burden to the individual, the family, and society [16], [17]. In rare yet severe progression, the disease may transform into malignant lesions [14], or in 1–3% of cases, may spread to the lower respiratory tract, entailing high mortality [11].

Individual studies have analyzed the risk factors associated with the occurrence and severity of JoRRP but findings have not been consistently replicable. Various published reviews have described the clinical manifestations and treatment options [12], [16], [18], [19], [20], [21], [22], [23], [24], [25], [26]. None, however, has focused systematically on etiology and prognosis. This systematic review, by summarizing recently published data, seeks to provide an up-to-date understanding of the risk factors for acquisition and severity.

Section snippets

Search strategy

We conducted a comprehensive systematic review of studies investigating risk factors associated with the acquisition and severity of JoRRP. We searched EMBASE, MEDLINE and Evidence-Based Medicine Reviews (EBMR) databases using the OvidSP interface with the following combinations of keywords and Boolean operators: (Laryn$ OR respiratory) AND (HPV OR papilloma or Papillomaviridae OR Papillomavirus Infections) AND (Disease* OR lesion* OR infection*) OR (Juvenile onset recurrent papillomatosis OR

Description of included studies

Our initial search identified 1362 citations. Of these, we retrieved 102 unduplicated full-text articles that conformed to eligibility criteria (Fig. 1). We found 14 additional studies from the reference lists. We retained 32 studies altogether, of which three [30], [31], [32] focused on risk factors for both acquisition and severity of disease.

All 32 studies were observational and together reported on a total of 2287 JoRRP cases. Seven studies included both JoRRP and adult-onset recurrent

Discussion

JoRRP is a relatively rare disease. Prospective studies are therefore difficult to undertake. In this comprehensive systematic review, we found that most (24/32) of the studies on JoRRP were indeed retrospective, corresponding to a low-moderate level of evidence as determined by the Oxford Center for Evidence-based Medicine [28]. Some had limitations such that results had to be interpreted with caution: some simply described JoRRP cases without controls [49], [51]; others used a case–control

Conclusions

Many children are exposed to HPV, but few develop JoRRP. Maternal genital condylomas during pregnancy and delivery (vertical transmission) are the major risk factors for JoRRP acquisition, while the HPV-11 genotype and younger age at which a child develops JoRRP lesions are important determinants of severity and prognosis. Genetic and immunological profiles play a role in the incidence and aggressiveness of JoRRP. Most of the underlying factors for disease acquisition and clinical course are

Acknowledgements

The authors are grateful to Danielle Buch, medical writer/editor at the Applied Clinical Research Unit of the CHU Sainte-Justine Research Center, for critical revision and substantive editing of the manuscript. HT received a salary award from the Fonds de la recherche du Québec-Santé.

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      Citation Excerpt :

      Clinically, two forms of RRP are recognized: juvenile onset RRP (JoRRP) and adult onset RRP (AoRRP), with 18 generally being the cut-off age for the JoRRP [5]. HPV transmission with RRP development at pediatric age is still unclear, but it is believed to occur vertically through the birth canal from a mother carrying genital condyloma during vaginal delivery [6]. However, the cesarean does not show a protective effect and the indication of this procedure only occurs in cases of bleeding or obstruction of the birth canal by the genital lesions.

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