(701) Aggression and Incidence: An IPD Meta-Analysis of Age-Related Severity in Recurrent Respiratory Papillomatosis

Introduction: The epidemiology of RRP is described as having a trimodal incidence pattern with peaks at ages 7, 35, and 64. Here we present an individual participant data (IPD) meta-analysis which examines the relationship between age of onset and disease aggression, as measured by surgical frequency. Unlike juvenile-onset RRP, where younger age at diagnosis is a recognized predictor of more aggressive disease, the relationship between age of onset and clinical severity in adult-onset RRP (AoRRP) remains poorly characterized.

Methods: A systematic review was performed to identify studies reporting IPD for AoRRP. A one-stage IPD meta-analysis was conducted using a linear mixed-effects model with restricted maximum likelihood (REML) estimation. The approach controlled for study-level heterogeneity using each paper as a random effect. The primary outcome was surgical frequency (surgeries/year). Age of onset was analyzed using both decade binning and stratification into ages 18-29 (young adult), 30-59 (middle age), and 60+ (senior).

Results: 14 studies meeting inclusion criteria yielded 196 adult patients. Incidence peaked at 30-39 years of age, reinforcing the existing epidemiologic peak. Onset in the young adult group was associated with more aggressive treatment at a surgical frequency of 1.69 surgeries per year. Onset in middle age had a surgical frequency of 1.16 surgeries per year, a statistically significant reduction of 31% (p=0.04). Onset in the senior age group had a surgical frequency of 1.57 surgeries per year but did not significantly differ from either of the other age groups. In analysis of different decades, the 20s and the 60s had the highest surgical frequencies of 1.68 and 1.71, respectively. The decrease from the 20s to the 30s was statistically significant (p=0.02), but other decades did not differ amongst themselves.

Conclusions: This IPD meta-analysis identifies a severity curve in AoRRP distinct from the incidence. Clinical aggression peaks in the 20s and 60s, and patients in these age brackets should be counseled on potentially more frequent surgical treatment compared to those who present in middle age.