Genetic dysregulation in recurrent respiratory papillomatosis

Abstract

Objectives/Hypothesis Recurrent respiratory papillomatosis (RRP) is a devastating disease, caused by infection of the upper aerodigestive tract with human papillomavirus types 6 and 11. There is no cure for RRP, and surgical removal is the mainstay of treatment. The purpose of this project was to compare genes of cell cycle, apoptosis, and inflammatory cytokines in laryngeal papilloma versus normal tissue for a better understanding of the molecular mechanisms of the disease to discover novel therapies. Study Design Basic science research study. Methods Papilloma tissue was obtained from patients requiring surgical debridement. For comparison, normal mucosa was obtained from the excised uvula of patients undergoing uvulopalatopharyngoplasty. Total RNA was extracted from both groups and then probed using customized reverse transcriptase real time polymerase chain reaction gene arrays. Results The custom arrays examine expression of 84 separate genes within the cell cycle, apoptosis, and inflammatory cytokine pathways. Our findings based on 11 papilloma samples run in comparison to normal mucosa shows that the MCL–1 gene of the apoptosis pathway is significantly downregulated. cytokine genes IL1-A, IL-8, IL-18, and IL-31 are also significantly dysregulated. Conclusions Genes of cell cycle and apoptosis are generally upregulated and downregulated, respectively, as expected in papilloma tissue, with MCL-1 achieving significance when compared to normal tissue. The finding of particular interest is that inflammatory cytokine genes were significantly downregulated, including IL1-A, IL-18, and IL-31. This finding may explain why patients infected with the virus are unable to mediate a T-cell immune clearance of their disease.

Comprehensive multiomic characterization of human papillomavirus-driven recurrent respiratory papillomatosis reveals distinct molecular subtypes

“…We observed the expression of angiogenic chemokines such as CXCL8 (IL-8) and VEGF within papillomas, consistent with previous findings 22 – 24 . The expression of IL-8 and VEGF was increased within the differentiated subgroup samples.…”

Concurrent oral human papilloma virus infection in patients with recurrent respiratory papillomatosis: A preliminary study

“…The current investigation does not deal with issues of immune clearance, which may also play a role in the persistence of HPV infection in the larynx and oral cavity of these patients. It has been suggested that RRP patients may have an inherent immune deficiency that prevents them from clearing the HPV infection . If true, this deficiency could explain the increased presence of HPV in the oral cavity of these patients.…”

Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1

“…High-risk HPVs are known to suppress apoptosis in infected cells [ 28 ], and apoptosis may play a role in vocal fold epithelial diseases [ 29 ]. However, evidence for changes in apoptosis in human RRP lesions is equivocal [ 30 , 31 , 32 , 33 ]. Cell–cell junctions in vocal folds are primarily tight junctions; adherens junctions and gap junctions are also present [ 20 , 34 ].…”