Long-term predictors of recurrence in pediatric recurrent respiratory papillomatosis

To identify predictors of recurrence in pediatric recurrent respiratory papillomatosis (RRP) using a 10-year prospective cohort, evaluating traditional factors (HPV type, lesion characteristics) and novel patient- and disease-specific variables, and their association with Speech-Quality-of-Life (SQOL).

We conducted a multicenter, prospective cohort study of 740 patients (629 pediatric, 111 adult) with histologically confirmed RRP from 2014 to 2023 at five high-volume ENT centers in Pakistan. The primary cohort comprised pediatric patients (onset < 18 years); while adult-onset cases were analyzed as a secondary comparative cohort to evaluate pediatric onset as an independent predictor of recurrence. Data included demographics, HPV type (6, 11, 16, 18), lesion number/location, surgery type, adjuvant therapy, tracheostomy history, age at onset, prior surgery intervals, lesion growth rate, socioeconomic status (SES), comorbidities, and immunodeficiency. The primary outcome was time to first recurrence requiring surgical intervention. Patients without recurrence were censored at their last follow-up visit. Time-to-event outcomes were analyzed using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression adjusting for all covariates. Standardized lesion assessment demonstrated high inter-rater reliability (kappa = 0.78).

Recurrence occurred in 65.0% of pediatric patients versus 45.9% of adult-onset patients (p < 0.001)Independent predictors included pediatric onset, HPV types 11, 16, 18, multiple lesions, tracheal involvement, younger age at onset, faster lesion growth, low SES, immunodeficiency, and shorter prior surgery intervals. Adjuvant therapies were associated with reduced recurrence (Cidofovir HR 0.62; Interferon HR 0.66; Bevacizumab HR 0.53). Surgery type did not independently predict recurrence. Median follow-up was 6.8 years. Lower SQOL scores correlated with higher recurrence frequency (Pearson r = - 0.52, p < 0.001).

Recurrence in pediatric RRP is multifactorial. Novel predictors-lesion growth rate, SES, and immunodeficiency-enhance risk stratification. Adjuvant therapies show associative benefit, and SQOL correlates with recurrence, highlighting the clinical importance of functional outcomes.