Global epidemiology of HPV-associated recurrent respiratory papillomatosis and effect of vaccination

By RY Seedat & FG Dikkers

Recurrent respiratory papillomatosis (RRP), caused by human papillomavirus (HPV), results in the development of papillomas in the respiratory tract [1]. The larynx is the most frequently affected site, with the trachea being the most common site of extralaryngeal involvement [2]. Other extralaryngeal sites that may be involved include the nose, nasopharynx, oral cavity, oropharynx and lungs.

Patients initially present with progressive dysphonia, but stridor and respiratory distress occur as upper respiratory tract obstruction develops [2]. Other symptoms may include chronic cough, recurrent upper respiratory tract infections and hemoptysis.

RRP is classified into two clinical types based on age at diagnosis: juvenile-onset RRP (JoRRP) and adult-onset RRP (AoRRP). JoRRP is believed to be acquired during birth from themother’s infected genital tract, while AoRRP is believed to be sexually transmitted [1]. RRP has been shown to have a trimodal distribution in the age at diagnosis in Europe, with peaks in the age at diagnosis of 7, 35 and 64 years [3]. However, this trimodal age at diagnosis has not been demonstrated in sub-Saharan Africa, where a bimodal distribution has been found, with peaks in the age at diagnosis at 5 and 45 years, and the overwhelming majority of patients are in the juvenile-onset group [4]. There is no difference in the sex distribution between males and females with JoRRP, while AoRRP occurs more commonly in males.

There is no cure, and treatment consists of repeated microlaryngoscopic procedures to remove the papillomas while attempting to preserve normal laryngeal tissue, until the patient goes into remission [2]. Repeated surgical procedures frequently lead to complications, such as anterior laryngeal synechiae, anterior glottic stenosis, posterior glottic stenosis and granuloma formation. Patients with airway obstruction may require a tracheostomy. Adjuvant treatments that have been used in the treatment of RRP including indole-3-carbinol, vaccination with mumps, MMR or HPV vaccines, IFN-α, cidofovir, programmed cell death protein 1 (PD-1) inhibitors and bevacizumab.