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Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 19-23

Pediatric laryngeal papillomatosis: A review

1 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Department of Oral Pathology and Microbiology, IDS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India

Date of Submission26-May-2019
Date of Decision13-Jan-2021
Date of Acceptance14-Jan-2021
Date of Web Publication19-Feb-2021

Correspondence Address:
Prof. Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aiao.aiao_11_19

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Laryngeal papillomatosis in pediatric age is an uncommon disease caused by the human papillomavirus which presents as warty, exophytic growths in the larynx. Child suffering from laryngeal papillomatosis frequently present with hoarseness of voice. In aggressive form laryngeal papillomatosis, it can lead to severe airway obstruction. Papillomas in the larynx often appear as exophytic nodules and this disease unpredictable in nature with spontaneous regression to aggressive persistent or recurrent disease. Fiberoptic laryngoscopy is helpful for identification of the lesions, whereas helical computed tomography is highly accurate for identification and of the disease and assessing the laryngeal airway. The definitive diagnosis is made by biopsy with histopathological examination. Surgical excision is the treatment of choice using microdebrider, CO2, or potassium titanylphosphate laser and coblation or cold steel instruments. The surgical complications may lead to vocal fold scarring, granulation tissue, webbing, and laryngeal stenosis. Coblation and Microdebrider are safe and cost effective than laser and coblation. Only maternal risk factor was primparous. Children with laryngeal papillomatosis associated with multiple surgeries in the past due to recurrence and aggressive nature of the diseases. Very young child and patients with tracheostomy need strict follow-up in case of sever diseases. In this review article, we disczuss the epidemiology, etiopathology, clinical presentations, diagnosis, and current treatment options of pediatric laryngeal papillomatosis.

Keywords: Cidofovir, coblator, laryngeal papillomatosis, microdebrider, pediatric

How to cite this article:
Swain SK, Das A, Sahoo L, Debta P. Pediatric laryngeal papillomatosis: A review. Ann Indian Acad Otorhinolaryngol Head Neck Surg 2020;4:19-23

How to cite this URL:
Swain SK, Das A, Sahoo L, Debta P. Pediatric laryngeal papillomatosis: A review. Ann Indian Acad Otorhinolaryngol Head Neck Surg [serial online] 2020 [cited 2023 Apr 2];4:19-23. Available from: https://www.aiaohns.in/text.asp?2020/4/2/19/309783

  Introduction Top

Laryngeal papillomatosis is usually seen in otolaryngology practice where small benign tumors grown in the larynx and sometimes adjacent structures. Human papillomaviruses (HPV 6 and HPV 11) are associated with this disease in a causal relationship.[1] Laryngeal papillomatosis in pediatric patients is rare clinical entity with unpredictable nature. These lesions have predilection for obstructing the laryngeal airway. Papilloma may be seen anywhere in the larynx but are most often found around the free edge and surface of the vocal folds, especially the anterior commissure.[2] They rarely extend into the trachea and bronchi apart from in very aggressive disease which need repeated and frequent debulking. In severe cases, treacheostomy may be required for getting patent airway although this is rare. Laryngeal papillomatosis was first described by Marsellus Donalus as warts in the throat in the 17th century.[3] Pediatric cases of laryngeal papillomatosis are often associated with first born; young prime gravid mothers and low socioeconomic standard.[4] The principal treatment of laryngeal papillomatosis is still surgical and aiming to clear the airway and improve the voice quality. There is no cure of recurrent laryngeal papillomatosis, but surgical excision is an accepted method for controlling of the disease and so prevent airway blockage. This review article focuses on the epidemiology, etiopathogenesis, clinical presentations, diagnosis, and current treatment of pediatric laryngeal papillomatosis.

  Method of Literature of Search Top

Research articles regarding pediatric laryngeal papillomatosis were searched through a multisystemic approach. First, we conducted an online search of the PubMed, Scopus, and Medline databases with the word pediatric laryngeal papillomatosis. There is a limited research work on pediatric laryngeal papillomatosis in comparison to other laryngeal pathology among children.

  Epidemiology Top

The laryngeal papillomatosis has bimodal presentations, i.e., seen among children and young adults. The juvenile form of laryngeal papillomatosis usually seen in patients of <20 years of age.[5] The pediatric form is often aggressive and found as multiple papillomatosis lesions and has high recurrence rate.[6] The approximate incidence of laryngeal papillomatosis in pediatric age is 4/100,000.[7] The incidence of laryngeal papillomatosis varies according to factors such as socioeconomic status, educational status, and age of the appearance.[8] It is higher among the children with lower socioeconomic status and low educational levels.[8] The incidence of laryngeal papillomatosis is higher among girl child or female.[8] HPV infections in pediatric patients often occur during birth at birth canal of contaminated mothers. Transmission of this virus can also occur through placenta in approximately 12% of cases.[8] Anogenital warts of mother are a risk factor of pediatric laryngeal papillomatosis during pregnancy. Around 0.7% of infants exposed to anogenital warts may give rise to laryngeal papillomatosis.[9]

  Etiopathology Top

Laryngeal papillomatosis is chronic viral disease caused by HPV mostly type-6 and 11. HPV is a DNA virus of the papillomaviridae family having propensity to infect epithelial cells. It has a nonencapsulated, double chain icosahedra structure and consists of 72 capsomered around 55 nm in diameter.[10] The risk factor for HPV transmission is higher for children with young, primiparous mothers with condylomas. HPV infection occurs often at birth during passage through birth canals of infected mothers. Before birth, transmission may occur through placenta. The presence of maternal anogenital warts during pregnancy period is considered as primary risk factor for pediatric laryngeal papillomatosis. Laryngopharyngeal reflux may be risk factor for laryngeal papillomatosis among pediatric patients by activating or reactivating a latent HPV infection.[11] HPV initially affects the basal epithelial layer of the larynx through minor excoriation. Then, it activates the epidermal growth factor receptor pathway and inhibits tumor-suppressing proteins. These mechanisms lead to cauliflower-like exophytic growth lesions in larynx, i.e., laryngeal papillomatosis.[9] Histopathologically, laryngeal papillomas appear as multiple fronds or projections with central fibrovascular cores covered with stratified squamous epithelium. The typical pictures are hyperplasia of basal cells and large vacuolated epithelial cells with clear cytoplasm. HPV often leads to delay in epithelial maturation causing thickened basal layer and increased nucleated cells in suprabasilar layer of the stratified epithelium. These lesions seen most often in transitional zone between the squamous epithelium and the ciliated columnar epithelium.[12] Papillomatosis growth in larynx may appear as exophytic, sessile, or pedunculated lesions and often limited to the larynx but often involving vocal folds, ventricles, subglottis, and laryngeal surface of the epiglottis.[13] However, it can be seen in any part of the aerodigestive tract. It is less seen in distal airway. Although laryngeal papillomas are benign in nature histologically, it may lead to dysplasia and malignant transformation.[6] In case of malignant transformation, pathological changes are sheets of polygonal tumor cells with abundant eosinophilic cytoplasm and vesicular nuclei, keratinization atypia, focal of necrosis, and variable mitotic rate with microinvasion growth.

  Clinical Presentations Top

Laryngeal papillomatosis is a rare lesion in the larynx with unpredictable nature of this disease. If it left untreated, child with laryngeal papillomatosis may present with hoarseness of voice and aggressive presentations often lead into stridor or sometimes transforms into malignant changes.[14] Infants or young children presenting with symptoms of voice change along with obstructive airway symptoms or recurrent croup warrants laryngoscopic examination. Glottic and supraglottic regions of the larynx are commonly affected by papillomatosis [Figure 1]. The progression of this disease is unpredictable. Although spontaneous resolution may happen, there is tendency toward recurrence and progression despite all types of treatment. Pediatric patients of laryngeal papillomatosis diagnosed before 3 years have worse prognosis than older children.[15] Death occurs in laryngeal papillomatosis due to complications of frequent surgical procedures or by respiratory obstruction or respiratory failure by distal disease progression. Macroscopically, laryngeal papilloma may be pedunculated or sessile which spreads over the mucosal lining of the larynx. These lesions are not friable so can be grasped by microlaryngeal forceps and excised for histopathological examination. The clinical presentations of laryngeal papillomatosis are variable. It often presents with nonspecific symptoms such as chronic cough, hoarseness, stridor, and rarely dysphagia. Because of this nonspecific clinical presentations, this disease can mimic to common laryngeal diseases such as laryngitis, asthma, bronchitis, and croup and so easily misdiagnosed, especially in children.[13] The differential diagnosis of laryngeal papillomatosis is different granulomatous lesions such as Wegner's granulomatosis, amyloidosis, tuberculosis, and sarcoidosis.[16]
Figure 1: Fiberoptic laryngoscopic picture showing laryngeal papilloma in vocal folds

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  Diagnosis Top

The diagnosis of laryngeal papillomatosis is usually done by direct laryngoscopy or fiberoptic nasopharyngolaryngoscopy. Bronchoscopy can be done to find out any lesions at the tracheobronchial tree below the larynx. Laryngeal papillomas appear as whitish polypoidal mass with clean and smooth surface, localized to the larynx.[1] Histopathological examination of the mass give definite diagnosis of the laryngeal papillomatosis.[6] The microscopic picture shows papillomas seen as exophytic projections of keratinized squamous epithelium overlying a fibrovascular core [Figure 2]. Koilocytes (vacuolated cells with clear cytoplasmic inclusions) are often found indicating viral infections. Helical computed tomography (CT) scan is the standard imaging for the assessment of laryngeal papillomatosis and assesses the laryngotracheal airway. Virtual bronchoscopy is an alternative method for CT scan where it visualizes the airway on three dimensional images. Chest X-ray is rarely done to diagnose this disease. In case of pulmonary involvement by laryngeal papillomas, chest X-ray may show solid or cavitated pulmonary nodules.
Figure 2: Microphotograph showing histopathological picture of laryngeal papillomatosis

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  Treatment Top

The mainstay of treatment is by surgical debulking. The aim of the treatment in laryngeal papillomatosis is removal of papillomas and restoration of patent and safe airway with minimal trauma to the mucosa and vocal folds. The chance of scarring and web formation can be reduced by avoiding two opposing raw surfaces, particularly at the anterior commissure. Extensive laryngeal papillomatosis of pediatric patients often requires repeated extirpations but often impossible to achieve normal voice.[17] Coblation is a minimally invasive low heat method which delivers a plasma layer for dissolution of the target tissues. The wands of the coblation are designed to function at 40°C–70°C, so minimize heating, charring, or burning. Introduction of powered microdebrider is relatively newer development in surgical removal of laryngeal papillomas and now becoming the gold standard for removal of laryngeal papillomas.[18] A nonserrated laryngeal blade is usually used with a setting of 300–700 rpm which make papillomas to be suctioned into the debrider with minimal trauma to surrounding normal tissues. The laryngeal blades help comprehensive and gentle removal of papillomas with minimal contamination of the lower respiratory tract with blood or papillomas. Use of endoscope makes it more precise with minimal damage to the mucosa. There is no thermal trauma to the surrounding tissues. One study demonstrated that laryngeal papilloma debridement has better disease clearance with shorter procedure and less postoperative pain in comparison to the CO2 laser.[19] Light amplification by stimulated emission of radiation (LASER) in the form of CO2 or potassium titanylphosphate has been used for debulking of laryngeal papillomas. However, LASER causes thermocoagulation damage to the underlying laryngeal tissue of the child,[20] whereas use of microdebrider in laryngeal papillomas is not associated with thermocoagulation damage to the underlying laryngeal tissues. In cold steel surgery, laryngeal papilloma is removed with the help of microlaryngeal instruments by the use of a microflap technique. It minimizes injury to the vocal fold while satisfying disease clearance. In cold steel method, thermal damage to the adjacent tissues is also avoided. It has distinct disadvantage of having no hemostasis when removing a vascular lesion. Surgery cannot prevent the recurrence of the disease, so different adjuvant therapies are often given to the patients. The complete removal of the lesions may lead to recurrences in many patients due to latent virus. In pediatric patients, approximately five surgeries a year needed to prevent recurrences.[5] The type of surgery often decides the surgical outcome. There is high chance of recurrence or complications after surgery due to repeated manipulation of the larynx. There is increased chance of anterior glottic synechia and is frequently encountered complications.[21] Posterior glottic and anterior commissure synechia also occur in 0.8%–12% and 3.6%–11.9% of the patients, respectively.[14],[22] Laryngeal or tracheal stenosis is seen in up to 14% of cases.[21] Other less common complications seen such as granulations and laryngoceles.[23] Adjuvant treatment can be divided into antiviral therapies and medications with antiproliferative or immunomodulatory properties.[5] The adjuvant therapies such as interferon alpha, photodynamic therapy, indol-3-carbinol, cis-Retinoic acid, acyclovir, ribovarin, cidofovir, and therapeutic vaccines are often expensive to be adopted routinely in Indian perspective.[24] Cidofovir is a cytosine nucleotide analog which selectively inhibit viral DNA polymerase during replication of virus. In recurrent respiratory papillomatosis, it can be administrated intravenously or through nebulization or by intralesional injection. Adjuvant intralesional cidofovir is helpful for partial or total regression of the lesions and reduce the frequency of surgical treatment.[25] Intralesional injection has advantage for maintaining low plasma level so that toxicity will be minimized without any side effects.[25]

Interferon is one of the adjuvant medications in laryngeal papillomatosis which give positive results in terms of disease evolution by causing reduction of the lesion growth.[26] The limitation of the interferon when given in intravenous route lead to systemic toxicity with reversible rise in serum transaminase level and possibility for thrombocytopenia and leukopenia.[2] Common side effects of interferon are fatigue, transient fever, nausea, arthralgia, headache, and spastic diplegia in infants. At present, topical application of interferon alpha is tried, but it needs further studies in patients with laryngeal papillomatosis.[27] The development of vaccines against HPV provides potential for the future eradication of the diseases by decreasing the incidence and so that prevent transmission of the virus. The quadrivalent vaccine is often given for the prevention of cervical and anogenital malignancies and precarcinogenetic lesions due to HPV subtype 6, 11, 16, and 18.[9] Currently, HPV vaccines are not approved for the use in neonates, so it needs further research.[28] Tracheostomy may be needed for extensive disease with a serious risk of obstruction at laryngeal airway, especially when several interventions have failed.[29] In comparison to HPV subtype 6, infection with HPV11 appears to be more likely to result in extensive disease with tracheostomy.[1] When tracheostomy done in laryngeal papillomatosis, decannulation must be performed as soon as airway is adequate and disease is controlled as tracheostomy site provides an additional site for rapid colonization of virus and serves as a conduit for spread of the disease to distal airway.[1]

The decreasing incidence of cases remains unexplained may be due to limited epidemiological data. The present protocol for increasing immunization (better antenatal care) may possibly be a few of the important factors involved. The present management protocols for Indian patients are governed by norms of the Western world. It may be possible to have racial, ethnical, and biological difference in the behavior of the disease in Indian subcontinent.

  Conclusion Top

Laryngeal papillomatosis is a viral disease, and the clinical behavior of this lesion in pediatric age is unpredictable. The prognosis of this lesion is on other hand recurrence, is again unpredictable. In the present day, increasing immunization, better antenatal care, or judicious antibiotic use may be useful for reducing the laryngeal papillomas in clinical practice. Laryngeal papillomatosis in children with the past history of surgeries often have aggressiveness nature of the disease. Very young child and child with tracheostomy tube should receive a strict follow-up in future. Coblators and microdebrider are ideal techniques for debulking of laryngeal papillomatosis. However, the review article will definitely encourage the future research work in the laryngeal papillomatosis in pediatric patients.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Donne AJ, Hampson L, Homer JJ, Hampson IN. The role of HPV type in recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 2010;74:7-14.  Back to cited text no. 1
Harries ML, Juman S, Bailey CM. Recurrent respiratory papillomatosis in the larynx: Re-emergence of clinical disease following surgery. Int J Pediatr Otorhinolaryngol 1995;31:259-62.  Back to cited text no. 2
Cohn AM, Kos JT, Taber LH, Adem E. Recurrent laryngeal papilloma. Am J Otolaryngol 1981;2:129-32.  Back to cited text no. 3
Moreddu E, Lambert E, Kacmarynski D, Nicollas R, Triglia JM, Smith RJ. Risk factors for severity of juvenile-onset recurrent respiratory papillomatosis at first endoscopy. Eur Ann Otorhinolaryngol Head Neck Dis 2019;136:25-8.  Back to cited text no. 4
Reeves WC, Ruparelia SS, Swanson KI, Derkay CS, Marcus A, Unger ER. National registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 2003;129:976-82.  Back to cited text no. 5
Marchiori E, Araujo Neto CD, Meirelles GS, Irion KL, Zanetti G, Missrie I, et al. Laryngotracheobronchial papillomatosis: Findings on computed tomography scans of the chest. J Bras Pneumol 2008;34:1084-9.  Back to cited text no. 6
Goon P, Sonnex C, Jani P, Stanley M, Sudhoff H. Recurrent respiratory papillomatosis: An overview of current thinking and treatment. Eur Arch Otorhinolaryngol 2008;265:147-51.  Back to cited text no. 7
Venkatesan NN, Pine HS, Underbrink MP. Recurrent respiratory papillomatosis. Otolaryngol Clin North Am 2012;45:671-94.  Back to cited text no. 8
Wilcox LJ, Hull BP, Baldassari CM, Derkay CS. Diagnosis and management of recurrent respiratory papillomatosis. Pediatr Infect Dis J 2014;33:1283-4.  Back to cited text no. 9
Fusconi M, Grasso M, Greco A, Gallo A, Campo F, Remacle M, et al. Recurrent respiratory papillomatosis by HPV: Review of the literature and update on the use of cidofovir. Acta Otorhinolaryngol Ital 2014;34:375-81.  Back to cited text no. 10
Formánek M, Komínek P, Jančatová D, Staníková L, Tomanová R, Vaculová J, et al. Laryngopharyngeal reflux is a potential risk factor for juvenile-onset recurrent respiratory papillomatosis. Biomed Res Int 2019;2019:1-5.  Back to cited text no. 11
Awad R, Shamil E, Aymat-Torrente A, Gibbins N, Harris S. Management of laryngeal papillomatosis using coblation: Another option of surgical intervention. Eur Arch Otorhinolaryngol 2019;276:793-800.  Back to cited text no. 12
Katsenos S, Becker H. Recurrent respiratory papillomatosis: A rare chronic disease, difficult to treat, with potential to lung cancer transformation: a propos of two cases and a brief literature review. Case Rep Oncol 2011;4:162-71.  Back to cited text no. 13
Karatayli-Ozgursoy S, Bishop JA, Hillel A, Akst L, Best SR. Risk factors for dysplasia in recurrent respiratory papillomatosis in an adult and pediatric population. Ann Otol Rhinol Laryngol 2016;125:235-41.  Back to cited text no. 14
Armstrong LR, Derkay CS, Reeves WC. Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP Task Force. Arch Otolaryngol Head Neck Surg 1999;125:743-8.  Back to cited text no. 15
Taliercio S, Cespedes M, Born H, Ruiz R, Roof S, Amin MR, et al. Adult-onset recurrent respiratory papillomatosis: A review of disease pathogenesis and implications for patient counseling. JAMA Otolaryngol Head Neck Surg 2015;141:78-83.  Back to cited text no. 16
Ruiz R, Achlatis S, Verma A, Born H, Kapadia F, Fang Y, et al. Risk factors for adult-onset recurrent respiratory papillomatosis. Laryngoscope 2014;124:2338-44.  Back to cited text no. 17
Tasca RA, Mc Cormick M, Clarke RW. British association of pediatric otorhinolaryngology members experience with recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 2006;70:1183-7.  Back to cited text no. 18
El-Bitar MA, Zalzal GH. Powered instrumentation in the treatment of recurrent respiratory papillomatosis: An alternative to the carbon dioxide laser. Arch Otolaryngol Head Neck Surg 2002;128:425-8.  Back to cited text no. 19
Böttcher A, Jowett N, Kucher S, Reimer R, Schumacher U, Knecht R, et al. Use of a microsecond Er: YAG laser in laryngeal surgery reduces collateral thermal injury in comparison to superpulsed CO2 laser. Eur Arch Otorhinolaryngol 2014;271:1121-8.  Back to cited text no. 20
Preuss SF, Klussmann JP, Jungehulsing M, Eckel HE, Guntinas-Lichius O, Damm M. Long-term results of surgical treatment for recurrent respiratory papillomatosis. Acta Otolaryngol 2007;127:1196-201.  Back to cited text no. 21
Yiu Y, Fayson S, Smith H, Matrka L. Implementation of routine HPV vaccination in the management of recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 2019;128:309-15.  Back to cited text no. 22
Mesolella M, Motta G, Laguardia M, Galli V. Papillomatosis of the larynx: Treatment with CO2 laser. B-ENT 2006;2:51-4.  Back to cited text no. 23
Mishra A, Singh DB, Verma DB. Recurrent respiratory papillomatosis: National registry. Indian J Otolaryngol Head Neck Surg 2013;65:85-8.  Back to cited text no. 24
Tasca RA, Clarke RW. Recurrent respiratory papillomatosis. Arch Dis Child 2006;91:689-91.  Back to cited text no. 25
Lee JH, Smith RJ. Recurrent respiratory papillomatosis: Pathogenesis to treatment. Curr Opin Otolaryngol Head Neck Surg 2005;13:354-9.  Back to cited text no. 26
Young DL, Moore MM, Halstead LA. The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice 2015;29:223-9.  Back to cited text no. 27
Omland T, Akre H, Vårdal M, Brøndbo K. Epidemiological aspects of recurrent respiratory papillomatosis: A population-based study. Laryngoscope 2012;122:1595-9.  Back to cited text no. 28
Carifi M, Napolitano D, Morandi M, Dall'Olio D. Recurrent respiratory papillomatosis: Current and future perspectives. Ther Clin Risk Manag 2015;11:731-8.  Back to cited text no. 29


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