Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Farrel J Buchinsky,Brian J Wiatrak,Fen Z Hu,John E Mcclay,Steven E Sobol,Charles M Myer,Garth D Ehrlich,Stephen F Conley,Sukgi S Choi,Craig S Derkay,Domingos H Tsuji,John M Schweinfurth,Joseph Donfack,J Christopher Post,Howard E Rockette,Paolo Campisi,Esper Georges Kallas

doi:10.1371/journal.pone.0002263

Abstract

BackgroundRRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course.Methodology/Principal FindingsPapilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age.Conclusions/Significance The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Highlights

It is well established that human papilloma virus (HPV) causes recurrent respiratory papillomatosis (HPV) [1]
By using both allele specific PCR and RFLP typing on all cases we were able determine whether human papillomavirus (HPV) 6 versus HPV 11 was present in the papilloma
For many years investigators have explored the relationship between the clinical course, and whether the patient was infected by HPV type 6 or type 11, but many studies suffered from small sample size

Summary

Introduction

It is well established that human papilloma virus (HPV) causes recurrent respiratory papillomatosis (HPV) [1]. The most common types associated with the vast majority of RRP are HPV 6 and 11[2,3]. While millions of children and adults are exposed, relatively few develop clinical evidence of the disease. The age of disease onset is highly variable and so is the clinical course [4]. While the presence of HPV is necessary to develop RRP it is not sufficient by itself. RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course

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Conclusion