Laryngopharyngeal Reflux Is a Potential Risk Factor for Juvenile-Onset Recurrent Respiratory Papillomatosis

Abstract

Introduction. Human papillomavirus (HPV) causes juvenile-onset recurrent respiratory papillomatosis (JORRP). Although HPV is common in children, the prevalence of JORRP is low. It is likely that other factors contribute to the pathogenesis of JORRP, during either activation or reactivation of a latent HPV infection. There is evidence that laryngopharyngeal reflux (LPR) might be such a risk factor for adult-onset recurrent respiratory papillomatosis. This study investigated if LPR might also be a risk factor for JORRP. Materials and Methods. Children with JORRP of the larynx that required microlaryngoscopy at a tertiary referral hospital were included in this prospective case-series study from November 2015 to November 2017. Using immunohistochemistry, HPV infection and pepsin associated with LPR were diagnosed from laryngeal biopsies. Results. Eleven children (aged 4-14 years) were analyzed. No patient had a history of immunodeficiency or tobacco smoke exposure. All patients underwent at least three previous surgeries due to JORRP and had been vaccinated against HPV in the past. Five children were treated using antivirotics and immunomodulators. The only known maternal risk factor was that three mothers were primiparous. All 11 samples were infected with HPV (type 6 or 11). Pathologic LPR was diagnosed in 5/11 children (45.5%). Conclusion. LPR may be a risk factor for JORRP, contributing to its development by activating or reactivating a latent HPV infection. Results are in accordance with those from our previous study in adults.

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

“…87 Pepsin has been detected inside the mucosal cell cytoplasm of 45.5% of children with RRP, suggesting that laryngopharyngeal reflux may be a risk factor for JoRRP, contributing to its development by activating or reactivating latent HPV infection. 88 Patients with clinical features suggestive of GERD should therefore be treated with a H2-antagonist or proton pump inhibitor. 56 Of the three currently available HPV vaccines, the bivalent vaccine (Cervarix ® ), quadrivalent vaccine (Gardasil ® ), and nonavalent vaccine (Gardasil ® 9), two (Gardasil ® and Gardasil ® 9) protect against HPV6 and HPV11.…”

Involvement of Laryngopharyngeal Reflux in Select Nonfunctional Laryngeal Diseases: A Systematic Review

“…From these, 64 were related to VF granuloma, 129 to laryngotracheal stenosis, 100 to laryngeal infections, and 48 to leukoplakia. Among these articles, 31 met our inclusion criteria and were kept for analysis ( Figure 1 ): 8 related to VF granuloma ( Table 1 ), 20-27 4 to laryngeal infections ( Table 1 ), 28-31 5 to leukoplakia ( Table 2 ), 7,32-35 and 10 to laryngotracheal stenosis ( Table 3 ). 36-45 Four additional basic research studies were identified concerning the relationship between reflux and the development of laryngotracheal stenosis.…”

“…Four studies focused on the relationship between LPR and chronic laryngeal infections—namely, laryngeal papillomatosis 28,30,31 and methicillin-resistant Staphylococcus aureus (MRSA). 29 The papillomatosis articles are described in Table 1 .…”

“…7,32,39,42,45 The objective approaches used for the reflux diagnosis included x-ray 20 ; gastrointestinal endoscopy findings 20,34 ; single-probe, 20,43 dual-probe, 21-23,28 triple-probe, 36,40 or oropharyngeal 41 pH monitoring; manometry 20 ; and pepsin detection. 30,31,35 Impedance pH was used in 1 study, but the authors did not consider the nonacid data. 44 Among the group of studies using pH monitoring without impedance, the criteria used for diagnosing LPR varied substantially.…”

“…28 This potential association was supported by the studies of Formanek et al, who identified pepsin in 25% to 45% of excised laryngeal papillomatosis tissue. 30,31 The proportion of pepsin was significantly higher in their patients as compared with the VF biopsies of healthy individuals. 30…”