In Situ Hybridization Signal Patterns in Recurrent Laryngeal Squamous Papillomas Indicate That HPV Integration Occurs at an Early Stage
E Brooks, MF Evans, CSC Adamson, Z Peng, V Rajendran, R Laucirica, K Cooper. University of Vermont/Fletcher Allen Health Care, Burlington, VT; Baylor College of Medicine, Houston, TX
Background: Laryngeal papillomas are histologically benign tumors that frequently recur. They may spread throughout the respiratory tract and can compromise airways. Children have a higher incidence than adults (4.3 vs. 1.8 per 100,000). The overall prevalence of HPV (mostly low-risk HPV genotypes 6 and 11) in these papillomas has been estimated at 76 percent; HPV11 may be associated with a more aggressive disease course. This study investigates HPV genotype, physical status, and protein expression, in relation to papilloma recurrence in children and adults.
Design: Forty-seven archival laryngeal papilloma specimens were obtained from nine children (ages 1 16 years) and fourteen adults (ages 16 82 years). In cases of recurrent respiratory papillomatosis (6 children, 10 adults), the first and last papillomas were assayed. HPV type was determined by GP5+/6+ PCR of sample DNA extracts followed by dot blot hybridization. In situ hybridization (ISH) was performed on thirty-eight specimens; the data were recorded in terms of diffuse (episomal HPV) and punctate (integrated HPV) signal patterns. Immunohistochemistry for the HPV L1 capsid protein, a marker of HPV productive status, was performed on thirty-four samples.
Results: All forty-seven samples tested HPV positive: overall, HPV11 was identified in 2/9 (22.2%) children and in 7/13 (53.9%) adults with single infections [p=0.2]; 7/9 children and 6/13 adults tested HPV6 positive; a recurrent HPV6/11 double infection was noted in one adult. HPV11 was identified in 1/6 (16.7%) children and in 6/9 (66.7%) adults with recurrent papillomas [p=0.12]. ISH signals (punctate diffuse) were detected among 6/9 (66.7%) child and 11/13 (84.6%) adult patients. Among patients with recurrent papillomas, punctate signals ( diffuse) were found in the first as well as the most recent sample. L1 staining was detected in 1/9 (11.1%) children and in 6/10 (60%) adults [p=0.057].
Conclusions: These data support the idea that integration of low-risk HPV types into the cell genome is an early and important event in the etiology of recurrent laryngeal papillomas of both children and adults. Larger studies are required to investigate the apparent abrogation of the productive HPV life-cycle (due to integration) in children. Further studies are also warranted to examine whether HPV11 is more prevalent in adulthood than childhood laryngeal papillomas.
Category: Head & Neck
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 168, Monday Morning