title: Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles.
abstract: In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7-32.9) for JoRRPs and 4.0 years (IQR 0.8-11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or -11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs.
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Oslo University Hospital, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
authors.forename: Turid
authors.initials: T
authors.lastname: Omland
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Oslo University Hospital, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
authors.forename: Harriet
authors.initials: H
authors.lastname: Akre
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Kathrine A
authors.initials: KA
authors.lastname: Lie
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Peter
authors.initials: P
authors.lastname: Jebsen
authors.affiliation: Department of Biostatistics, Oslo University Hospital, Oslo, Norway; University of Oslo, Faculty of Dentistry, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Oslo University Hospital, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
authors.forename: Kjell
authors.initials: K
authors.lastname: Brøndbo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D015331:Cohort Studies; D005838:Genotype; D054884:Host-Pathogen Interactions; D052140:Human papillomavirus 11 / Q000235:genetics; D052163:Human papillomavirus 6 / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000502:physiology*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D015995:Prevalence; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D012307:Risk Factors