ABSTRACT
OBJECTIVES/HYPOTHESIS: To determine oral human papilloma virus (HPV) colonization in patients with adult-onset recurrent respiratory papillomatosis (AO-RRP) and their long-term partners. STUDY DESIGN: Prospective, cohort study METHODS: Patients with pathology-confirmed AO-RRP and a small cohort of their long-term partners were subjected to a standardized oral rinse and swab protocol to obtain oral epithelial cells. DNA from these samples was extracted and subjected to both qualitative analyses via multiplex polymerase chain reaction as well as to a commercially available linear array assay for the determination of specific HPV subtypes. RESULTS: Samples were collected from 27 patients with AO-RRP and six long-term sexual partners. Qualitative analysis of agarose gel products using a multiple genotype primer cocktail suggested the presence of HPV DNA in oral rinse or swabs in 26 patients (96%) and four partner samples (67%). A subset of these positive patient samples was then subjected to genotyping; a spectrum of HPV subtypes was observed. Interestingly, HPV81 was identified in many samples. CONCLUSION: Recent data suggest that less than 7% of the general population is HPV positive in the oral cavity. Our data suggest that the oral colonization rate is much higher in patients with AO-RRP. Additionally, long-term sexual partners of patients with RRP had a much higher rate of HPV positivity. These preliminary data may have implications for viral transmission and provide a framework for enhanced patient education as well as further investigation. LEVEL OF EVIDENCE: 4.
Subject(s)
DNA, Viral/genetics , Mouth Diseases/virology , Mouth Mucosa/virology , Papillomaviridae/genetics , Papillomavirus Infections/virology , Respiratory Tract Infections/virology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Genotype , Humans , Male , Middle Aged , Mouth Diseases/diagnosis , Mouth Diseases/epidemiology , Mouth Mucosa/pathology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Polymerase Chain Reaction , Prevalence , Prospective Studies , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Risk Factors , United States/epidemiologyABSTRACT
OBJECTIVES/HYPOTHESIS: To determine the efficacy of small interfering RNA (siRNA) targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal regulation of Smad3 following vocal fold (VF) injury, and to determine the local and distal effects of Smad3 siRNA VF injection. STUDY DESIGN: In vitro and in vivo. METHODS: In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA ± transforming growth factor ß (TGF-ß). Collagen transcription was also examined. In vivo, Smad3 messenger RNA (mRNA) expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites. RESULTS: Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-ß-mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites. CONCLUSIONS: These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally delivered siRNA for challenging fibrotic conditions of the VF.
Subject(s)
Gene Expression Regulation , Laryngeal Diseases/genetics , RNA, Messenger/genetics , Smad3 Protein/genetics , Vocal Cords/pathology , Animals , Blotting, Western , Cells, Cultured , Electrophoresis, Polyacrylamide Gel , Fibrosis/genetics , Fibrosis/metabolism , Fibrosis/pathology , Genetic Therapy/methods , Humans , Immunohistochemistry , Laryngeal Diseases/metabolism , Laryngeal Diseases/pathology , Male , RNA, Small Interfering/pharmacology , Rabbits , Reverse Transcriptase Polymerase Chain Reaction , Smad3 Protein/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta1/genetics , Vocal Cords/drug effects , Vocal Cords/metabolismABSTRACT
OBJECTIVES/HYPOTHESIS: We hypothesize that the KTP laser has the potential to augment wound healing in a rat model, and this modality may serve as a therapeutic tool for the management of vocal fold fibrosis. STUDY DESIGN: Prospective, laboratory animal study. METHODS: Rats were subjected to either vocal fold injury ± KTP laser treatment at low energy to simulate clinically relevant endpoints. In addition, cohorts were subjected to therapeutic KTP laser alone. Endpoints included the analyses of gene expression data related to the acute inflammatory response and extracellular matrix deposition and organization. RESULTS: Therapeutic KTP treatment was associated with an additive effect on inflammatory gene expression in the context of the injured rat vocal fold mucosa. A similar additive effect was observed for matrix metalloproteinase gene expression, similar to data previously reported in the dermatology literature. However, histologically, the KTP had little effect on established vocal fold fibrosis. CONCLUSIONS: These data are the first to attempt to provide mechanistic insight into the clinical utility of angiolytic lasers for vocal fold scar. Similar to previous data obtained in the skin, it appears that these effects are mediated by MMPs.
