Therapeutic use of the HPV vaccine in recurrent respiratory papillomatosis: A case report


Recurrent Respiratory Papillomatosis (RRP) is a condition characterized by recurring squamous papillomas in the aerodigestive tract due to Human Papilloma Virus (HPV) infection. Treatment includes surgical debridement of the lesions often with adjuvant therapy. A newer adjuvant agent being tested is the HPV vaccine. The case report includes a child with RRP who underwent 10 surgeries in a year with an average inter-surgical interval (ISI) of 46 days. The patient then received the scheduled regimen of 3 doses of 9 valent HPV vaccine. Since beginning the vaccination, her average ISI increased to 113 days and as of writing of this paper only 1 surgery in the last 340 days. It is theorized that the increase in humoral response to the virus can slow the course of the disease, lengthen the ISI, and decrease morbidity. The results of this case report lends evidence to the use of the HPV vaccine as a therapeutic adjuvant therapy for RRP.


Recurrent Respiratory Papillomatosis (RRP) is a condition more commonly observed in the pediatric population than in adults and results in the growth of squamous papillomas in the aerodigestivetract [1]. It most commonly affects the larynx and often recurs by spreading through the aerodigestive tract [2]. These growths can cause airway compromise, leading to dysphonia, respiratory distress, and complete occlusion. This condition is generally caused by Human Papilloma Virus (HPV) infection, with the vast majority caused by HPV serotypes 6 and 11 [3]. While the mode of transmission isn’t fully understood, it is theorized that vertical transmission of HPV from mother to baby occurs by ascending infection due to exposure to HPVþ papillomas in the genital tract by the newborn or intrauterine transplacental infection. Sexual intercourse, self-inoculation, and horizontal transmission through saliva have also been described and more commonly affect older children and adults. This disease has an incidence of 4.3 cases in 100,000 in children, and 1.8 cases in 100,000 in adults [2]. The treatment of these cases results in over $150 million a year [1]. In children who were born to women with active condyloma there was a 231-times increased risk of RRP, and a 2-fold risk for children born from extended labor [4]. While the strong association between the presence of maternal condyloma with extended labor indicates perinatal exposure to HPV in the genital tract during the birth process as a major risk factor, C-section is not indicated as intrauterine transplacental infection may also play a role in transmission of the virus and only 1 in 400 children with perinatal exposure to HPV condyloma went on to develop RRP [5].

The majority of cases involve frequent and recurrent treatments. The mainstay of treatment involves surgical removal of the papillomas to maintain the patency of the airway. Surgery is done using cold microsurgery, laser microsurgery, or removal using a microdebrider. These surgeries rarely prevent recurrence of the papillomas and these patients frequently require multiple surgeries [6]. On average, a child with RRP will require 4.9 debridement surgeries per year. The number of procedures per year significantly increases if the child was diagnosed with RRP under the age of 2 years old [7]. These surgical procedures do not completely eliminate the HPV, so the use of adjuvant therapy can help reduce the recurrence of papillomas. Adjuvant therapies commonly used include cidofovir and bevacizumab, but many other treatments have been tried including methotrexate, interferon, cimetidine, mumps vaccine, ribavirin, acyclovir, photodynamic therapy, and indole-3-carbinol [6,8,9]. Some adjuvant therapies, especially cidofovir, have provided good response against RRP. However, significant side effects of these adjuvant therapies most significantly including nephrotoxicity with cidofovir alongside uncertain long term effectiveness of many adjuvant therapies drives the development of newer therapies. One new adjuvant therapy that has been used more recently as a treatment is the HPV vaccine. There are several case studies that show good results from and a case series showing no benefit from the HPV vaccine, however there are no randomized clinical trials outlining its efficacy [10e16]. The purpose of this paper is to discuss an individual case of pediatric RRP treated with the HPV vaccine and review the current literature in regards to its treatment role.