Abstract
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.
Highlights
Recurrent respiratory papillomatosis (RRP) is a rare condition characterized by recurrent growth of benign papillomas in the respiratory tract (Figure 1), most commonly in the larynx. [1,2] The disease is categorized as juvenile-onset (JoRRP) if it develops before the age of 18, and adult-onset (AoRRP) for cases that develop after the age of 18
[14] Women with a history of genital warts have an increased risk of cervical intraepithelial neoplasia (CIN) and cervical carcinoma, most likely due to co-infection with ‘high-risk’ human papillomavirus (HPV) genotypes (HR-HPV). [15,16] Anogenital tract carcinomas and their precursors are linked to infection with HR-HPV, primarily HPV 16 and 18. [17,18] The proportion of HPV related head and neck carcinomas (HNSCC), oropharyngeal carcinomas, has been rising in recent decades among young adults and in non-smokers. [19,20,21,22,23] Similar to all other HPV related cancers, HPV 16 is the most common genotype identified in HNSCC
All HPV-positive patients were infected by HPV 6 or HPV 11, which is in line with similar studies with the prevalence of HPV 6 or HPV 11 infection to be in the range of 70–98%. [4,5,6] Comparable to RRP, more than 90% of the genital warts contain HPV type 6 (55–90% of cases) or type 11 (5–42%). [45,46,47] In the immunosuppressed individuals, the presence of HPV 11, multiple HPV infections and HR- HPV is higher
Summary
Recurrent respiratory papillomatosis (RRP) is a rare condition characterized by recurrent growth of benign papillomas in the respiratory tract (Figure 1), most commonly in the larynx. [1,2] The disease is categorized as juvenile-onset (JoRRP) if it develops before the age of 18, and adult-onset (AoRRP) for cases that develop after the age of 18. [4,5,6,7,8] These ‘low risk’ HPV genotypes (LR-HPV) cause anogenital condylomas. [24] RRP is a benign neoplasm, progression to carcinoma can occur in 3–7% of cases. LR-HPV may, in rare cases, be associated with malignancy, including carcinoma in the anogenital region. [15,16] Anogenital tract carcinomas and their precursors are linked to infection with HR-HPV, primarily HPV 16 and 18. Many of these publications are more than 20 years old and based on small series or case reports. Many of these publications are more than 20 years old and based on small series or case reports. [25,26,27,28,29,30,31,32] The mechanisms of malignant transformation in RRP, and whether it is preceded by HPV driven precursor lesions, are not clear. [33]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
