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.
A retrospective epidemiological study of patients treated for idiopathic subglottic stenosis (ISS) during 2003–2013 at Oslo University Hospital, Rikshospitalet, was undertaken to assess its incidence, management and treatment outcomes. Out of a total of 123 patients with subglottic stenosis (84 female, 39 men), 38 patients were diagnosed with ISS, all of whom were female. Of these, 23 lived in the South-Eastern Norway Regional Health Authority, representing an incidence of 0.2 per 100,000 (95% CI 0.13–0.3) in this region of 2.9 million inhabitants. Mean age at diagnosis was 54 years (range 20–85 years), and the mean interval between symptom onset and diagnosis was 3.1 years. The 38 patients with ISS underwent a total of 132 operations between 2003 and 2013. All patients were managed endoscopically using laser surgery, with or without corticosteroids and Mitomycin C, with dilatation by balloon or bougie. Eight patients (21.1%) required only one procedure, while 30 patients (78.9%) had multiple operations. The median follow-up for all patients from the first operation was 5.3 years. The mean interval between procedures was 1 year for patients aged 20–48 years, 1.3 years for patients aged 49–61 years and 3.0 years for patients aged 62–85 years. No clinically significant complications were observed. In conclusion, the symptoms of ISS can be treated effectively with laser surgery and dilatation but the recurrence rate remains high and the time interval between operations does not increase with time, making ISS a continuing challenge.
Since 1995 patients with T1a glottic carcinomas have been treated with laser surgery at the Department of Otorhinolaryngology, Rikshospitalet in Oslo. During this period we have in many cases noticed an inconsistency between the clinical outcome and the histopathological report describing that the resection margins were not free. We wanted to investigate this discrepancy, and the charts with the histopathological reports of 171 patients treated between 1995 and 2005 have been reviewed. Seventeen patients (10%) experienced a recurrence of the initial disease and were treated by repeated laser surgery, radiotherapy, or radiotherapy and laryngectomy. Two patients (1%) had died from the disease. In 36% of the cases (62 patients) the histopathological report indicated "not free" or "probably not free" resection margins. The discrepancy between the histopathological reports and the clinical outcome reflects the pathologist's difficulty in orienting and determining resection margins in laser-resected specimens. Because of the low number of recurrences or metastases, the verdict of a violated resection margin should probably not be crucial for further treatment. The surgeon's peroperative judgement may be trusted, however, with very close follow-up in order to detect early recurrences.
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