Recurrent respiratory papillomatosis (RRP)–time for a reckoning?

Abstract

ObjectivesRecurrent respiratory papillomatosis (RRP) is a rare disease, but one with severe morbidity and occasional mortality. The aetiological agent is human papillomavirus (HPV), and HPV types 6 and 11 account for over 90% of all cases. In the active phase of the disease, patients require multiple hospital admissions for surgical removal or ablation of these benign tumors, which are likely to obstruct the airways if left unchecked. Long‐term sequelae include scarring of the vocal cords, change in voice timbre, or even muteness if a tracheostomy is required. The aim of this study was to determine if adjuvant vaccination with the quadrivalent HPV L1 vaccine (Gardasil™) would decrease numbers of surgical treatments post‐vaccination.MethodsA prospective pilot study following a cohort of 12 RRP patients, all of whom gave fully informed consent to participate. All patients had their papillomas typed and if they were found to have types 6 or 11, were vaccinated at the time of first surgical treatment in the hospital, according to the manufacturer's protocols. Patients were followed up closely with 3 or 6 month follow‐up visits. Standard surgical treatments were given and were not affected by whether they participated in the study.ResultsWe found a >7‐fold decrease in the incidence rates of papillomatosis requiring surgical intervention from the pre‐vaccination period (47.44/1000 patient‐months) compared to the post‐vaccination period (6.71/1000 patient‐months).DiscussionSurgical treatments for RRP are robust markers for papillomata which require treatment because of the dangers of obstruction of the airway. Despite the small size of this cohort (due to the rarity of this disease), the data suggests that adjuvant use of quadrivalent HPV L1 vaccine imparts significant benefit to this group of patients. A large multi‐center randomized placebo controlled trial is required to definitively establish whether this hypothesis is true and can become the new standard of therapy.Level of Evidence3b

In RRP, serologic response to HPV is frequently absent and slow to develop

“…Some surgeons have conducted such interventions under a research protocol and have published their observations. Several showed a serologic response [36,37] to the vaccine and an increase in the time between surgeries [5,6,38,39]. Hermann et al [7] and Milner et al [8]found no such difference.…”

“…Several years have passed since the study was executed and the preliminary results were communicated via poster and oral presentation. Since then there has been interest in the feasibility of using the quadrivalent HPV (qHPV) vaccine as a treatment modality for RRP [5][6][7][8][9][10].…”

Therapeutic Use of the Human Papillomavirus Vaccine on Recurrent Respiratory Papillomatosis: A Systematic Review and Meta-Analysis

“…Patient subgroups not relevant to our study were excluded from the study population before statistical analysis along with patients with any malignant disease or pre-malignant laryngeal lesions (n=3) [13]. In the meta-analysis, we further excluded seven patients with less than 24 months of follow-up after vaccination (four patients from Hočevar-Boltežar et al [28] and three patients from Goon et al [31])…”

“…Only a few original studies addressing the therapeutic use of the HPV vaccine as treatment for RRP have been published [13,16,[25][26][27][28][29][30][31][32] along with a small number of case reports [33][34][35][36][37][38][39]. The reported outcomes vary, and a proposed large-scale multicenter study has not yet been undertaken.…”

Papillomatosis of the larynx in children: the current state of the problem

“…Известно, что в определенных клеточных системах гены ВПЧ, кодирующие структурные белки вириона L1 и L2, способны осуществлять не только синтез соответствующих белков, но и формирование так называемых вирусоподобных частиц (VLP-viruslikeparticles). Эти частицы, не содержащие в своем составе ДНК вируса, обладают очень выраженной иммуногенной активностью [48].…”