Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis

Abstract

Abstract Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil ) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPVspecific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries

Introduction

Infection with a subset of human papillomaviruses (HPV) can cause anogenital cancer, oropharyngeal cancer, condylomata acuminata and recurrent respiratory papillomatosis (RRP) [1, 2]. Since 2006 many national vaccination programs have started with the bivalent HPV vaccine (Cervarix , GlaxoSmithKline Biologicals s.a., Rixensart, Belgium) or the quadrivalent HPV vaccine (Gardasil, Merck & co, Whitehouse Station, USA) targeting high-risk oncogenic HPV types 16 and 18. Papillomavirus vaccines are generally safe and highly effective [3]. The quadrivalent HPV vaccine is a subunit vaccine composed of the major capsid protein L1 primarily in the form of virus-like particles (VLPs) of low-risk HPV6 and 11 and high-risk HPV16 and 18. HPV6 and 11 cause 90 % of genital warts [4]. It is expected that preventive global use of this HPV vaccine against cervical cancer will decrease the incidence of HPV6 and HPV11 related disease worldwide [5]. Recurrent respiratory papillomatosis (RRP) is a wartlike disease characterized by its unpredictable clinical course. It is associated with HPV6 and 11 for 80–100 % of cases [6–10]. Therapy focuses on repeated surgical removal of exophytic lesions. Some patients may need over a 100 surgical interventions to keep the airway open and the voice sufficient [6]. Antibody response after vaccination with the quadrivalent HPV vaccine is higher than after natural infection in patients with high-risk HPV [3, 11]. Little is known about the antibody response for low-risk HPV. Increased seroreactivity after vaccination in RRP patients was only addressed in two case reports [12, 13]. After vaccination with the quadrivalent HPV vaccine, HPV seropositive women were protected against cervical and anogenital diseases from the corresponding HPV type [3]. Therefore, vaccination of RRP patients could be a potential treatment against HPV re-infection or auto-inoculation. In this independent exploratory study we investigated whether vaccination with the quadrivalent HPV vaccine results in increase of antibodies against the associated viruses.