Human papillomavirus and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis

Abstract

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 consecutive papillomas excised from 47 children between 1981 and 1996 at The New Children's Hospital in Sydney, Australia, were tested for human papillomavirus (HPV) DNA by PCR. PCR products from the viral upstream regulatory region (URR) enhancer were sequenced, and variation was related to clinical variables. Forty-four of the 47 children had HPV-induced papillomas, with type 11 accounting for 24 (55%) and type 6 accounting 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 significant association between HPV type and disease aggressiveness. One novel, large-scale URR duplication was identified in an HPV type 11 isolate in the last of a series of six papillomas examined and the first from the bronchus. However, the duplication was not found in HPV type 11 isolates from the associated pulmonary carcinoma and its metastases in other organs. Three of 14 URR point mutations coincided with transcription factor binding sites, but there were no obvious associations with clinical course. Chi-square and multiple linear regression analyses of clinicopathological variables revealed early age at diagnosis (less than 4 years) as an independent predictor of aggressive disease (P < 0.001). A bimodal distribution of the age at diagnosis was noted, with peaks at 2 and 11 years of age.

Juvenile respiratory papillomatosis: Risk factors for severity

“…Severe forms of recurrent respiratory papillomatosis were defined as any of the following: Derkay anatomical score ≥10, more than 10 surgeries overall or any tracheal involvement. This definition was selected to incorporate both the objective Derkay anatomical scale and the number of surgical procedures mostly used in the literature [Gabbott et al, ; Rabah et al, ; Draganov et al, ; Buchinsky et al, ].…”

“…There is a paucity of good quality data on risk factors associated with disease severity [Pou et al, ; Gabbott et al, ; Rimell et al, ; Armstrong et al, ; Rabah et al, ; Reeves et al, ; Bonagura et al, ; Wiatrak et al, ; Gerein et al, ; Draganov et al, ; Maloney et al, ; Leung et al, ; Buchinsky et al, ; Bonagura et al, ; Carvalho et al, ]. In most of the studies, HPV11 was associated with a worse prognosis [Rimell et al, ; Rabah et al, ; Gerein et al, ; Draganov et al, ; Maloney et al, ].…”

“…In most of the studies, HPV11 was associated with a worse prognosis [Rimell et al, ; Rabah et al, ; Gerein et al, ; Draganov et al, ; Maloney et al, ]. Other risk factors associated with increased severity included: young age of the children at diagnosis and maternal history of condylomas [Gabbott et al, ; Reeves et al, ; Silverberg et al, ; Wiatrak et al, ]. Due to the relatively rare incidence of recurrent respiratory papillomatosis compared to the high HPV prevalence in young women, genetic factors of the host were suspected to play a role in disease outcome.…”

Recurrent Respiratory Papillomatosis: A Longitudinal Study Comparing Severity Associated With Human Papilloma Viral Types 6 and 11 and Other Risk Factors in a Large Pediatric Population

“…The subtypes of HPV-6 were distinguished by restriction endonuclease digestion patterns, which may identify viral types less accurately than polymerase chain reaction (PCR). Gabbott et al 96 demonstrated no significant difference in disease severity in a population of 47 children with RRP over a 15-year period, with an equal distribution of HPV-6 (55%) and HPV-11 (43%). Padayachee and Prescott 97 reported more severe disease in children with HPV-6 versus HPV-11.…”

Recurrent respiratory papillomatosis

“…HPV types 6 and 11 account for most cases of RRP. HPV-11 occurs most commonly (50%-100% of isolates) [9][10][11][12][13][14] and runs the most aggressive clinical course, followed by HPV-6. HPV types 16, 18, 31, and 33 have also been reported in RRP, albeit rarely.…”