HUMAN-PAPILLOMAVIRUS AND WEST VARIABLES AS PREDICTORS OF CLINICAL COURSE IN PATIENTS WITH JUVENILE-ONSET RECURRENT RESPIRATORY PAPILLOMATOSIS

This study provides the first systematic evaluation of papillomavirus type and viral mutation occurring during the course of juvenile-onset recurrent respiratory papillomatosis. One hundred ninety-nine consecut ive papillomas excised from 47 children between 1981 and 1996 at The N ew Children's Hospital in Sydney, Australia, were tested for human pap illomavirus (HPV) DNA by PCR, PCR products from the viral upstream reg ulatory region (URR) enhancer were sequenced, and variation was relate d to clinical variables, Forty-four of the 47 children had HPV-induced papillomas, with type 11 accounting for 24 (55%) and type 6 accountin g for 19 (43%); one (2%) was positive for either type 6 or 11, Overall , 183 (98%) of the 186 samples with amplifiable DNA were HPV positive, There was no change in HPV type over time and no statistically signif icant association between HPV type and disease aggressiveness, One nov el, large-scale URR duplication was identified in an HPV type 11 isola te in the last of a series of six papillomas examined and the first fr om the bronchus, However, the duplication was not found in BPV type 11 isolates from the associated pulmonary carcinoma and its metastases i n other organs, Three of 11 URR point mutations coincided with transcr iption factor binding sites, but there were no obvious associations wi th clinical course, Chi-square and multiple linear regression analyses of clinicopathological variables revealed early age at diagnosis (les s than 4 years) as an independent predictor of aggressive disease (P < 0.001), A bimodal distribution of the age at diagnosis was noted, wit h peaks at 2 and 11 years of age.