Relationship between inflammation and the severity of Recurrent Respiratory Papillomatosis

Highlights

• There is difference between inflammatory cell population in juvenile and adult recurrent respiratory pappilomatosis.

• Adults showed significantly higher quantities of CD3+, CD8+ and MUM1+ cells than the juvenile patients.

• MUM-1+ cells were correlated with lower Derkay index.

Abstract

Objective

To characterize inflammatory cells in Recurrent Respiratory Papillomatosis (RRP) and to correlate it with severity using the Derkay laryngoscopic scale.

Materials and methods

The data and biopsies from 36 patients with Juvenile (JRRP) and 56 patients with Adult (ARRP) were collected and analyzed under light microscopy. The patients were separated into groups according to the Derkay index: ≥20 for the most severe and < 20 for the less severe cases. Immunohistochemical analysis using CD3, CD4, CD8, CD15, CD20, CD68, FoxP3 and MUM-1 antibodies was performed, and the inflammatory cells were quantified. All the clinicopathological characteristics and the results of the immunohistochemical analysis were compared among the groups proposed using the Chi-Square test and correlated through the Spearman correlation test.

Results

The ARRP showed significantly higher quantities of CD3+, CD8+ and MUM1+ cells (p < .05) than the JRRP samples. The presence of CD15+ cells showed positive correlation with the Derkay index (p < .05), while the MUM-1+ cells showed an inverse correlation (p = .01).

Conclusion

There are differences between the inflammatory cells population in the juvenile and adult groups and it can be related to disease severity.

Introduction

Recurrent Respiratory Papillomatosis (RRP) is a serious disease that occurs in two clinical forms: juvenile (JRRP) and adult (ARRP); the former occurs predominantly before 5 years of age and affects both females and males equally; the latter is prevalent in male patients between 20 and 40 years of age [1].

Human papillomavirus (HPV) infection is responsible for the development of the disease, primarily the low-risk types HPV 6 and 11 [1,2]. HPV type 6 is the most common [3,4] and type 11 is predominant in the most aggressive cases [1,5].

There are scales that assist in therapeutic decision-making and in the identification of aggressive cases, including: Voice Handicap Index-10 (VHI-10) [6], Roughness, Breathiness, Asthenia, Strain (GRBAS) [7] and the laryngoscopic scale of Derkay et al. (1998) [8].

The immune system is important in preventing lesion progression and encouraging HPV-infection clearance [9]. There are few studies correlating the aggressiveness of RRP to inflammation and the results are not uniform [10,11]. The severity of RRP has been correlated with greater numbers of CD83+ mature dendritic cells (DC) in the epithelium and there is evidence of the involvement of migration of these cells and their retention in the epithelial layer [11]. In RRP, the imbalance between Th1 and Th2 immune responses may contribute to the persistence of infection and recurrence of this disease [10].

Noting the important role of inflammation, or its absence, related to the above-mentioned disease, the present study aims to identify possible differences in the population of inflammatory cells secreting pro-inflammatory cytokines and chemokines between patients with low and high Derkay indexes.

The results may detect prognostic factors that lead to the early recognition of aggressive cases, and also determine possible causes that lead to the varied behavior of this disease that may occur in isolated cases, multiple relapses or spontaneous remission.