Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles.

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.

Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

Epidemiological aspects of recurrent respiratory papillomatosis: a population-based study.

OBJECTIVES/HYPOTHESIS: The incidence of genital infections, cervical cancer, and oropharyngeal cancer induced by human papillomaviruses (HPV) is increasing in Western countries. Primarily, this study was conducted to estimate the incidence rate of recurrent respiratory papillomatosis (RRP) in juveniles and adults in two Norwegian subpopulations for each year between 1987 and 2009. The secondary objective of the study was to investigate whether there are trends in the incidence rates of RRP in the study period similar to what we have seen for HPV-related cancer. STUDY DESIGN: Population-based study. METHODS: Two Norwegian subpopulations with 2.6 million and 1.1 million inhabitants were investigated for the juvenile and adult forms of RRP, respectively, between the years of 1987 and 2009. Patients treated for RRP were identified in all ear/nose/throat departments located in the two areas. RESULTS: The overall incidence rates of RRP in juveniles and adults were 0.17 (95% confidence interval [CI], 0.10-0.25) and 0.54 (95% CI, 0.44-0.65) per 100,000, respectively. We found a preponderance of males in both groups (P = .000 for adults and P = .038 for children). There was no significant change in the yearly incidence rate during the study period, for either adults or children, even when stratifying for gender in each group. The median age at onset was 4 years for children and 34 years for adults, with no significant difference between genders, nor significant changes during the study years. CONCLUSIONS: This study does not support our hypothesis of an increasing incidence of RRP, for either children or adults. The estimated incidence rates in the Norwegian subpopulations are consistent with former population-based studies. Male preponderance in children was an unexpected finding. Further studies are warranted.

Paradoxical vocal cord movement in newborn and congenital idiopathic vocal cord paralysis: two of a kind?

The second most common cause of stridor reported in the newborn is bilateral vocal cord paralysis (BVCP) and one-third of the cases have been categorized as idiopathic. During the last year four children with stridor since birth were referred to our department for examination. Videotaped flexible laryngoscopy, carried out with the patient awake or under general anaesthesia with a spontanous respiration, revealed instead of abduction of the vocal cords during inspiration, rather an active adductory movement. Consequently instead of BVCP, we made the diagnosis paradoxical vocal cord movement (PVCM). One of the twins required a tracheostomy, the three other patients have been observed without the need of further treatment. No previous publications have described PVCM in newborn. However, our observations and video recordings clearly show that the stridor in our four patients is due to PVCM. This is possibly the same condition as earlier reported as congenital, idiopathic BVCP where incoordinated vocal cord movement or dyskinesia has been a part of the laryngoscopic findings. The mechanism behind PVCM in this age group or site of lesion is unclear.