Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

OBJECTIVES/HYPOTHESIS: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma. STUDY DESIGN: An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed. METHODS: DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome. RESULTS: HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients. CONCLUSIONS: HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.

HLA-DQ alleles in white and African American patients with juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To determine HLA-DQalpha and -DQbeta1 allele associations in juvenile-onset recurrent respiratory papillomatosis (RRP) for risk, disease course, and human papillomavirus type. DESIGN: A nonrandomized controlled study was performed on DNA extracted from papilloma specimens of children with a history of RRP, and from peripheral blood of African American and white children without RRP. The frequencies of DQalpha and DQbeta1 alleles were compared between patients and ethnically matched controls. SUBJECTS: Records of 48 children treated for RRP at Children's Hospital of Michigan in Detroit (26 African American and 22 white) were reviewed. Control subjects consisted of 80 African American and 80 white children seen at the hospital for conditions other than RRP. RESULTS: African American and white patients with DQbeta1*050X (not *0501, *0502, *0503, *0504, or *0505) were at higher risk to develop RRP than controls (P =.01 and.03, respectively). DQbeta1*0402 was protective for African Americans (P =.01). Whites with DQalpha*0102 were at risk for RRP (P =.03). This allele was associated with disease remission in African Americans (P =.03). DQalpha*0101/0104 conferred protection in whites (P =.047). No association was seen for allele frequency and human papillomavirus type. Whites with haplotype DQalpha*0501/DQbeta1*0201 were at high risk for RRP (P =.002). No relationships were seen for African Americans or whites between haplotype frequencies and disease course or human papillomavirus type. CONCLUSIONS: HLA-DQalpha and -DQbeta1 alleles occur at different frequencies in African American and white children with RRP than controls. Specific alleles influence risk for RRP. Allele and haplotype frequencies have some influence on disease course, but were independent of human papillomavirus type.

Laryngeal effects of antigen stimulation challenge with perennial allergen Dermatophagoides pteronyssinus.

OBJECTIVE: We conducted a pilot study to assess the effects of antigen stimulation on the appearance and function of the larynx. STUDY DESIGN AND SUBJECTS: The prospective, double-blind, randomized study included 9 adult patients with a skin-prick test positive for Dermatophagoides pteronyssinus. MAIN OUTCOME MEASURES: Subjects were blindly challenged via nebulizer with either an active antigenic suspension or placebo. Baseline and 30-minute evaluations of the larynx were performed. Assessments included subjective voice and videostroboscopic assessments, acoustic analysis of voice, speech aerodynamic testing, and allergy and voice handicap questionnaires. RESULTS: Although both inflammation and increased mucus were noted, there were no significant differences between the antigen- and placebo-exposed subjects on any of the measures obtained. CONCLUSIONS: Our preliminary investigation was not successful in demonstrating a direct causal relationship between antigen exposure and physical or functional changes in the larynx. Future studies will involve modifications to our current methodology, including increasing the concentration of antigen, prolonging the exposure time, and observing for late phase responses.

Effects of sequential Dermatophagoides pteronyssinus antigen stimulation on anatomy and physiology of the larynx.

The goal of this investigation was to study the effects of sequential dust mite antigen stimulation on the appearance and function of the larynx. To that end, we designed a randomized, placebo-controlled, double-blind, prospective analysis of adults who had tested positive for perennial dust mite allergy. The larynx of patients who received the active antigen was challenged directly with a low (1:100) and a high (1:40) concentration of the dust mite allergen via an oral nebulizer. Voice laboratory assessment tools included voice and allergy questionnaires, videostroboscopic examination of the larynx, acoustic and speech aerodynamic analyses, and digital audio voice recordings. The study was prematurely terminated after 2 patients had been treated with the highest concentration of the antigenic suspension because of adverse effects, including chest tightness, coughing, and voice difficulties. Both of these patients had demonstrated viscous endolaryngeal secretions and vocal fold edema on videostroboscopy. No reactions were noted at the lower concentration of antigen exposure or in 1 control patient who completed the study. We believe that our findings, as preliminary as they are, may serve as an initial template for the differential diagnosis and treatment of other patients with inhalant allergies who present with chief complaints suggestive of allergic laryngitis.

Physiological change in nasal patency in response to changes in posture, temperature, and humidity measured by acoustic rhinometry.

BACKGROUND: Acoustic rhinometry has been used to assess nasal patency and to calculate nasal cavity volume. This study used acoustic rhinometry to assess changes in nasal patency after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. METHODS: Eight healthy adult volunteer subjects underwent acoustic rhinometry during the following conditions: (1) sitting position (control), (2) supine position, (3) left lateral recumbent position, (4) nostril unilaterally mechanically blocked, (5) ice pack on neck, (6) drinking cold water, (7) drinking hot water, (8) nasal nebulizer, and (9) oxymetazoline decongestant. RESULTS: Two distinct patterns emerged based on the total nasal cavity volumes in response to the decongestant. Subjects with initial unilateral nasal cavity volumes near the mean had an expected increase in total volume after the topical decongestant administration. There were two subjects with initial volumes of 1 SD above the mean that had a paradoxical decrease in total volume in response to the decongestant. In all subjects, there was a significant decrease in the volume of each of the nasal cavities in response to ingestion of hot water at 1 minute. There was a significant decrease in the volume of the smaller of the two nasal cavities in response to nebulizer treatment and hot water ingestion at 5 minutes. Total nasal cavity volume changes were not significant for any of the variables. CONCLUSION: Changes in nasal cavity volumes were detected by acoustic rhinometry after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. Nebulizer treatment and hot water ingestion caused a significant decrease in nasal volume. The nose of a healthy patient was able to adapt to environmental and physiological changes to maintain a consistent total nasal volume within 15 minutes.