Gardasil-4® as adjuvant therapy in Juvenile Onset Recurrent Respiratory Papillomatosis at Red Cross War Memorial Children's Hospital, South Africa: A retrospective review

Frank, Shavina

Gardasil-4® as adjuvant therapy in Juvenile Onset Recurrent Respiratory Papillomatosis at Red Cross War Memorial Children's Hospital, South Africa: A retrospective review

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Division of Otorhinolaryngology

Faculty

Faculty of Health Sciences

Abstract

Juvenile onset recurrent respiratory papillomatosis (JoRRP) is a benign disease of the upper aerodigestive tract that affects children 12 years and under (1). The incidence is 4 in 100 000 cases per annum in children (2). It is predominantly caused by the Human Papillomavirus (HPV) with subtypes 6 and 11, accounting for over 90% of cases. The most common sites for these papillomata are the larynx and trachea (3). Age at onset, specifically under the age of 5 years was found to be an independent risk factor for a more aggressive clinical course (4,5). HPV subtype 11 is reportedly also associated with a more aggressive form of the disease (6,7). There is no cure, and surgical clearance of the obstructed airway is the current standard of treatment. JoRRP has a varied course, but those with aggressive disease require multiple surgical interventions and, in some cases, a tracheostomy. There is also an associated malignancy risk of 7% (8). The repeated visits to hospital results in a high-cost burden to the patient, their family, and the health care system, with an estimated cost recorded to be between $120-$150 million annually in the United States(2,9), notwithstanding the associated significant morbidity and decreased disease-free quality of life years(9). There are various off-label adjuvant therapies under review. Historically, alpha-interferon, an immunomodulatory cytokine, was popular and used by many institutes world-wide (10). It fell out of favour during the early 2000s, due to its negative side effect profile on patients and its increased risk of malignant transformation (11). This allowed the opportunity for many other adjuvant therapies to be tested. Cidofovir®, an acyclic nucleoside phosphonate that inhibits viral replication and transcription was one such therapy (12–14). As HPV is a DNA virus, it was specifically selected because of its inhibitory effect on viral DNA replication and transcription. Cidofovir® showed a positive effect in reducing disease recurrence in other viral studies(15). In earlier publications, Cidofovir® was administered intra-lesionally for recurrent respiratory papillomas (12,13). Elective cyclo-oxygenase (COX)-2 inhibitors also showed promise by theoretically reducing the growth of papillomas and enhancing apoptosis of HPV-infected cells (16). This was thought to work by indirectly reducing epidermal growth factor receptors, which are commonly overexpressed in HPV infected cells, through the COX-2 pathway (16). However, studies have shown no improved clinical outcome.