Juvenile-Onset Recurrent Respiratory Papillomatosis: The Benefits of Quadrivalent Human Papillomavirus Vaccination Continue to Accrue

In this issue of the Journal of Infectious Diseases, Novakovic et al [1] provide the first report of a decline in juvenile-onset recurrent respiratory papillomatosis (JoRRP) attributable to a national quadrivalent human papillomavirus (qHPV) vaccination program in Australia. So eagerly was this outcome anticipated that it led to the establishment of new surveillance strategies [2, 3]. The decline also effectively confirms, as has been long suspected, that JoRRP is a consequence of the transmission of HPV type 6 or 11 from mother to child around the time of birth. A mother would need to be infected with HPV 6 or 11 to transmit the infection to her child. None of the mothers of the children with JoRRP had received the qHPV vaccine before the pregnancy [1]. Recurrent respiratory papillomatosis (RRP) comes in 2 forms distinguished by the age groups affected and probably the mode by which HPV is aquired [4]. Adult-onset RRP typically emerges in early adulthood, which is around the most common time that HPV is acquired by sexual transmission. By contrast, JoRRP appears in early childhood and usually runs a more aggressive clinical course, perhaps in part because infants have smaller airways or because of immune compromise [4]. Juvenile-onset recurrent respiratory papillomatosis has been attributed to vertical transmission in the mother’s birth canal and sometimes in utero during labour. The resultant wart-like lesions of RRP can be very recurrent and typically involve the larynx, but it can extend to the lower respiratory tract including the lungs, compromising the airway in a manner that is occasionally fatal [4]. In a clinical audit of Australian hospitals, 30 children with JoRRP required 375 admissions over an average of 40 months, mainly for ablative treatment of lesions via endoscopy. Surgical complications were common [2]. Australia has the highest coverage and had the quickest uptake of qHPV vaccination of any country in the world [5]. Therefore, it is not surprising that it is the first country to document a decline in the incidence of JoRRP. Since 2007, publically funded qHPV vaccine has been offered to all schoolgirls age 12–13 years, with a catch-up program for older schoolgirls and all women up to age 26 years. Nationally, coverage of schoolgirls was 83% for the first dose and 70% for the third dose [6]. Schoolboys were added to the vaccination program in 2013. The qHPV vaccine targets HPV types 6 and 11—the causes of anogenital warts and RRP—in addition to the oncogenic types 16 and 18. Benefits of Australia’s national qHPV vaccination program were evident early on: (1) declining HPV prevalence in young women, sufficient to provide herd protection to unvaccinated women [5, 7]; (2) declining high-grade cervical lesions in the youngest women [5, 8]; and (3) genital warts approaching elimination in young people [5, 9]. Given the long natural history of HPV-related cancers, however, it will take many more years to document and understand the full benefit of the vaccination program for cervical, vulval, anal, and oropharyngeal cancers attributable to HPV types 16, 18, and others. Because the median age at presentation is 36 months (range, 6 months to 14.5 years) [2], JoRRP can be described as a HPV-related disease with an intermediate incubation period. Thus, it was timely for Novakovic et al [1], working with the Australian Paediatric Surveillance Unit, to document a national decline in the incidence of JoRRP from 2012 to 2016. It is notable that despite the high qHPV vaccination coverage in young Australian women, none of the mothers of the 15 JoRRP-affected children in this study had received the vaccine before their pregnancies, and the 7 JoRRP cases subjected to genotyping were all positive for HPV 6 or 11. These findings are consistent with and reinforce other observations of the effect of the vaccination program on the prevalence of HPV 6 and 11 [7] and the incidence of anogenital warts [5]. Novakovic et al [1] E D I T O R I A L C O M M E N T A R Y