Recurrent Respiratory Papillomatosis: HPV Genotypes and Risk of High-Grade Laryngeal Neoplasia

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.

Impaired T Cell-dependent Humoral Immune Response Associated with Juvenile-onset Recurrent Respiratory Papillomatosis Progression

“…While persistent Human Papillomatosis Virus (HPV) type 6 or 11 virus infection is often associated with JORRP development5, emerging evidences showed that immune responses against HPV type 6 or 11 virus infection are the determinants of JORRP outcome6. It has been suggested that impaired cellular immune response in patients with JORRP support sustained HPV-6/11 infection and prevent HPV virus from clearance.…”

Cáncer de laringe y Virus del papiloma humano en adultos del Hospital Escuela Universitario, Honduras

“…En diferentes estudios reportan este dato como muy influyente en la infección por el VPH, sobre todo la práctica del sexo oral y la tenencia de múltiples parejas sexuales; (Omland et al, 2014), con respecto al antecedente de papilomatosis respiratoria recurrente, solamente en una (1) de las pacientes (femenina) existía el antecedente dudoso de esta afección, incluso con traqueotomía previa 20 años antes a la revisión del caso. Como fue mencionado antes, existe evidencia científica en la cual se considera a la papilomatosis laríngea recurrente como factor de riesgo para la carcinogénesis.…”

Prevalence of human papillomavirus-related diseases in the Republic of Korea: a cross-sectional study

“…According to international studies, the following percentages of disease cases are attributable to HPV: 100% for cervical cancer, 88.0% for anal cancer, 39.7% for vulvar cancer, 78.0% for vaginal cancer, 50.0% for penile cancer, 30.8% for oropharyngeal cancer, 2.2% for oral cavity cancer, 2.4% for laryngeal cancer,4 18 19 90% for genital warts1 and 90% for benign neoplasms of the larynx (ie, RRP) 2. As data on HPV-attributable percentages of CIS cases were unavailable, we assumed that these percentages were equal to those previously reported for cancer cases of corresponding anatomical sites.…”

“…Twelve high-risk types of HPV are associated with cancers of the cervix, vagina, vulva, anal canal, penis, oropharynx, oral cavity, larynx and oesophagus (online supplementary reference w1) while the low-risk HPV types (mainly types 6 and 11) chiefly cause genital warts in men and women1 and recurrent respiratory papillomatosis (RRP) 2…”