Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis

Abstract

Background Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. Methods A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. Results We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. Conclusion In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

<p>Juvenile-Onset Recurrent Respiratory Papillomatosis Diagnosis and Management – A Developing Country Review</p>

“…1 HPV types 6 and 11 are responsible for most cases of JoRRP, although other types, including high risk types have also been identified. [3][4][5]9,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Transmission of HPV is believed to occur during birth from the mother as the fetus passes through an infected genital tract. Although a minority of mothers of children with RRP have a history of previous genital condylomata, most have histologic evidence of HPV infection.…”

“…36 The triad of a firstborn child born by vaginal delivery to a teenage mother was first described by Kashima and has subsequently been found in a number of other studies. 4,21,29,37 Primigravid mothers are more likely to have a long second stage of labor with prolonged exposure to HPV in the birth canal, leading to a higher risk of infection in the first-born child.…”

“…2,4,7,16,[30][31][32][33][38][39][40] Patients with HPV11 disease present at a significantly younger age than those with HPV6 disease. 2,20,21,27 The initial presenting symptom is progressive dysphonia, followed by stridor and respiratory distress. 4,29,30,[38][39][40][41] Patients may be aphonic with respiratory distress on presentation.…”

“…29,31,62 However, younger age at diagnosis has been found to be associated with more aggressive disease, and has also been found to be a more significant marker of disease aggressiveness than HPV type. 16,20,21,63 Intratypic variants of high risk HPV types have been shown to have characteristic geographical distribution patterns and to have differing pathogenic potential. 64 Intratypic variants of HPV6 and HPV11 have been also been shown to vary by geographic area, but not to be as geographically restricted.…”

“…69 A maternal history of condyloma acuminata may be associated with aggressive RRP. 7,21,35 Management There is no cure and treatment consists of repeated microlaryngoscopic procedures to remove the papillomas until the patient goes into remission. Papilloma removal is either with a cupped forceps, laser (CO 2 , KTP, or flash dye), microdebrider or coblation, depending on the surgeon's preference and availability of equipment.…”