|Year : 2019 | Volume
| Issue : 3 | Page : 114-121
Pediatric Laryngeal Papillomatosis: Experiences at an Indian Teaching Hospital
Santosh K Swain, Ishwar C Behera, Loknath Sahoo
Department of Otorhinolaryngology and Community Medicine, Institute of Medical Sciences and SUM Hospital, Siksha “O” Anusandhan Deemed to be University, Bhubaneswar, Odisha, India
|Date of Submission||03-Aug-2019|
|Date of Acceptance||03-Sep-2019|
|Date of Web Publication||27-Nov-2019|
Dr. Santosh K Swain
Department of Otorhinolaryngology, Institute of Medical Sciences and SUM Hospital, Siksha “O” Anusandhan Deemed to be University, K8, Kalinganagar, Bhubaneswar 751003, Odisha.
Source of Support: None, Conflict of Interest: None
Background and Aims: Laryngeal papillomatosis is an uncommon disease in pediatric age caused by the human papilloma virus, which presents as warty, exophytic growths in the larynx. Children having laryngeal papillomatosis frequently present with dysphonia. It can lead to severe airway obstruction and voice change. The aim of this study was to assess the detailed clinical presentations, treatment options, and outcome of the laryngeal papillomatosis in pediatric patients. Materials and Methods: This was a prospective study carried out among pediatric age group (n = 21) and among those who underwent surgical treatment with different modalities such as coblation, microdebrider, and laser on diagnosed cases of laryngeal papillomatosis during December 2015 to March 2019. Clinical presentations and detailed patient profile including maternal aspects were documented. Details of previous surgeries conducted on the child’s larynx were also recorded. Results: Dysphonia is the most common clinical presentation. Of 21 children, 12 were boys and 9 were girls. The mean age was 11.52 years. No child with a history of immunodeficiency or exposure to smoking was reported. Of 21 children, 9 had a history of previous surgeries for laryngeal papillomatosis. There were five primiparous mothers in this study and they are considered as as risk factors. One child underwent tracheostomy due to compromised airway by laryngeal papillomatosis. Coblation and microdebrider are common and effective techniques performed among children with laryngeal papillomatosis. Conclusion: Coblation and microdebrider were found to be safe and cost-effective than laser and coblation. Only maternal risk factor in this study was primiparous mother. Children with laryngeal papillomatosis were associated with multiple surgeries in the past due to recurrence and aggressive nature of the disease. Very young children and patients with tracheostomy needed strict follow-up in case of severe diseases.
Keywords: Cidofovir, Coblator, Laryngeal papillomatosis, Microdebrider, Pediatric
|How to cite this article:|
Swain SK, Behera IC, Sahoo L. Pediatric Laryngeal Papillomatosis: Experiences at an Indian Teaching Hospital. J Health Res Rev 2019;6:114-21
|How to cite this URL:|
Swain SK, Behera IC, Sahoo L. Pediatric Laryngeal Papillomatosis: Experiences at an Indian Teaching Hospital. J Health Res Rev [serial online] 2019 [cited 2020 Mar 31];6:114-21. Available from: http://www.jhrr.org/text.asp?2019/6/3/114/271844
| Introduction|| |
Laryngeal papillomatosis is usually observed in otolaryngology practice where small benign tumors grow in the larynx and sometimes in adjacent structures. Laryngeal papillomatosis in pediatric patients is a rare clinical entity with an unpredictable nature. These lesions have predilection for obstructing the laryngeal airway. Papilloma may be seen at any part of the larynx, but the most common locations are vocal folds, especially anterior commissure. These lesions spread less frequently into the trachea and bronchi except in very aggressive variety, which needs repeated debulking of the growth. In aggressive variety, tracheostomy is needed for obtaining patent airway although this is rare. The causative agent for laryngeal papillomatosis is human papilloma viruses (HPV 6 and HPV 11). In seventeenth century, laryngeal papillomatosis was first described by Marsellus Donalus as wartlike lesion in the throat. Pediatric cases of laryngeal papillomatosis are often associated with the firstborn, young primigravid mothers, and low socioeconomic standard. The principal treatment of laryngeal papillomatosis is surgery, aiming to clean the airway and to enhance the voice quality. Laryngeal papillomatosis has no cure but decisional surgery is an accepted mode for controlling the disease and thus preventing airway blockage.
This study highlights our institutional experiences of pediatric laryngeal papillomatosis including the clinical behavior, treatment modalities, and outcome among the children at a teaching hospital in the eastern part of India.
| Materials and Methods|| |
This presented case series included 21 children who were diagnosed as having laryngeal papillomatosis and who were admitted in the department of otorhinolaryngology for treatment during December 2015 to March 2019. This is a prospective and comparative case series carried out at a teaching hospital in the eastern part of India. Diagnosed cases of laryngeal papillomatosis among children were selected by random sampling method. All these cases were previously diagnosed and confirmed by fiber-optic nasopharyngolaryngoscopy. This study was approved by Institutional ethical committee((IEC) with reference number:IMS/IEC/CRL/SOAU/91/12.11.2015. Informed consents were taken from parents of the children those participated in this study.
Inclusion criteria consisted of children with an age range from 5 to 18 years. Children presenting with hoarseness of voice and laryngeal examination showing papillomatosis growth were included in this study. The exclusion criteria included clinical diagnosis of laryngeal cancer, inflammatory lesions of the larynx, children with speech abnormalities due to central pathology, oral and oropharyngeal diseases of the children, and diseases of nose and nasopharynx affecting speech.
The diagnosis of laryngeal papillomatosis is based on the findings of direct laryngoscopy or fiber-optic nasopharyngolaryngoscopy. Laryngeal papillomas are seen as polypoidal mass with smooth surface, confined to the laryngeal structures.
All the children are diagnosed after confirmation with fiber-optic nasopharyngolaryngoscopy and the lesions were recorded by video monitor [Figure 1]. The duration of this disease, recurrence, treatment undertaken at the time of visit, need for tracheostomy, associated treatment, and overall follow-up were documented. Ten children were treated with coblators, seven were treated with microdebrider, and three were treated with laser. Laser provides minimal thermal injury to the adjacent tissue, adequate hemostasis, and precise excision of the lesion, but the disadvantages are more surgical period, high price, and special need for precautions to minimize the risk of fire in the airway and the spread of virus to the staff. Operative time and cost are less in case of microdebrider compared to that of laser. As the temperature generated in coblation is relatively less, the risk of fire in the airway, postoperative pain, and hospital stay are less. On these grounds, treatment options were compared in this study. All types of surgery were performed under general anesthesia with oral intubation. An operating laryngoscope was placed into suspension and the exophytic papilloma, causing airway obstruction [Figure 2], was debulked by coblator (Smith & Nephew, Watford, United Kingdom), microdebrider (Medtronic Xomed Debrider, Jacksonville, Florida, USA), or CO2 Laser (Lumenis CO2 surgical laser, New York). Laryngeal wand (LW) [Figure 3] was used to excise the papillomatosis growth in coblation technique. The appearance of wound after the excision of laryngeal papillomatosis by microdebrider is shown in [Figure 4] as intraoperative image. Hemostasis was achieved with the topical application of cotton ball soaked with adrenaline (1:1000) (adrenaline injection contains epinephrine, strength 1mg/mL, manufactured by Maya Biotech, Chandigarh, India). Coblation (radio-frequency ablation) debulking was carried out by using Procise LW (Massachusetts, USA). In case of laser debulking, CO2 laser was used with appropriate maintenance of laser safety. During debulking laryngeal papillomas by laser [Figure 5] or coblator or microdebrider, proper care was taken not to injure the deeper part and the adjacent area of the larynx. All surgeries were performed by senior surgeons.,
|Figure 2: Intraoperative image of the laryngeal papillomatosis before coblation|
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|Figure 3: Laryngeal wand used for excision of laryngeal papilloma in coblation technique|
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|Figure 4: Intraoperative image showing laryngeal wound after excision of laryngeal papilloma after coblation|
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|Figure 5: Intraoperative image of laser excision of the laryngeal papillomatosis|
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Biopsy specimens of laryngeal papillomas were taken during microlaryngeal surgery and were sent for histopathologic examinations. Cidofovir injection (2.5mg/mL) was injected directly in papillomatosis lesions of the larynx during microlaryngeal surgery under general anesthesia. Cidofovir was manufactured by Gilead Sciences (Foster City, California) and it was injected to subepithelial areas that were previously cleaned mechanically or with laser. Cidofovir was also infiltrated below the stroma of papilloma because of increased risk of adhesion following mechanical treatment. Dose of single drug ranged from 1 to 10mL (average, 3mL). None of the patients was given more than 3mg cidofovir per kilogram of body weight. Intralesional cidofovir injections were given in recurrent cases (nine cases) of this study. Prophylactic anti-reflux therapies with proton pump inhibitor (omeprazole-domperidone combination) were given to all patients for four weeks those underwent surgery where mucosal layer of the larynx disruption is expected.
Patient follow-up was carried out at three months, six months, and one year along with the documentation of complications of laryngeal airway due to surgery.
| Results|| |
This study consisted of 21 children (12 boys and 9 girls). The male children were found dominated to the girl.The mean age of the study population was 11.52 years. The youngest patient in this study was 5 years and the eldest was 18 years. The overall male/female ratio in this study population was 1.7:1. Recurrent cases were nine in number (those operated several times previously). The duration of clinical presentations at the time of first admission ranged from two months to nine years. Of the nine recurrent cases, four were with a single episode of recurrence within a period of six months, whereas four cases showed three or more episodes of recurrence within six months to three years. There was a history of maternal risk factor such as primiparous mother in five cases. The age of mothers in this study ranged between 22 and 29 years [Table 1].
Regarding perinatal background of this study, HPV transmission occurred from mother to child predominantly through vaginal route and only in two cases by cesarean section. Mothers of the children were not aware about any genital warts of HPV infections during pregnancy period. None of them had received specific vaccination against HPV previously. All children with laryngeal papillomatosis presented with hoarseness of voice. Of 21 children, 19 presented with dry irritating cough, 2 presented with dysphagia, and 2 presented with stridor [Table 2]. Two cases underwent tracheostomy for stridor with extensive papillomatosis obstructing the laryngeal airway [Figure 6]. Two patients with tracheostomy were rendered communicative by instituting a speech valve in the tracheostomy tube. Requirement of tracheostomy did not correlate with the frequency of recurrence. In the laryngeal papillomatosis, the treatment undertaken was primarily endoscopic surgical excision under general anesthesia. Ten cases underwent coblation, seven microdebrider, and three lasers [Table 3]. Intralesional cidofovir injection was administered in nine cases, which had a previous surgical history of laryngeal papillomatosis. One child was referred to pulmonary department to rule out extension into lower respiratory tract. One case showed recurrence after six months of surgery performed by laser. Complications due to surgery were documented during follow-up. One case of anterior commissure synechia, one of posterior commissure synechia, and one of glottic stenosis were detected [Table 4].
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|Table 2: Clinical presentations of the children affected with laryngeal papilloma|
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The glottic stenosis case underwent tracheostomy due to development of stridor. Histopathologic report confirmed squamous cell papillomas in all samples. Immunohistochemistry report revealed that HPV 6 was present in 18 samples, whereas HPV 11 was confirmed in three samples. All cases except one showed no evidence of recurrence. After six months of treatment, 13 cases recovered normal voice.
| Discussion|| |
The etiology of laryngeal papillomatosis is viral in origin and usually due to HPV, mostly types 6 and 11. HPV is a deoxyribonucleic acid (DNA) virus included in Papillomaviridae family with a tendency of invading epithelial cells. This virus has two chain icosahedra structure with no capsule and consists of 72 capsomeres around with a diameter of 55nm. Laryngeal papillomatosis is a rare lesion in the larynx with an unpredictable nature of disease. Infants or young patients presenting with hoarseness of voice along with breathing difficulty or croup warrant laryngoscopic examination. Glottic and supraglottic regions of the larynx are commonly affected by papillomatosis. The progression of this disease is unpredictable. Although spontaneous resolution may happen, a tendency toward recurrence and progression is observed despite all types of treatment. Pediatric patients of laryngeal papillomatosis diagnosed before three years have worse prognosis than older children. Death occurs in laryngeal papillomatosis due to laryngeal airway obstruction or complication occurring due to multiple surgical procedures in the larynx or progression of the disease to distal airway, leading to respiratory failure. Macroscopically laryngeal papilloma may be sessile or pedunculated in nature, which spreads on the mucosal surface of the laryngeal structures. These lesions are not friable so they can be picked up by laryngeal forceps and the removed mass can be sent for histopathologic test. The microscopic image of papillomas shows keratinized squamous epithelial lining with exophytic projections with fibrovascular core. The vacuolated cells with the presence of clear cytoplasmic inclusion are called as koilocytes, which are often seen, and they indicate the presence of viral infections. The clinical presentations of laryngeal papillomatosis are variable. It often presents with nonspecific symptoms such as chronic cough, hoarseness, stridor, and rarely dysphagia. As the signs and symptoms of the patients with laryngeal papillomatosis are nonspecific, it often confuses with diseases such as laryngitis, bronchial asthma, bronchitis, acute laryngotracheobronchitis, and is usually misdiagnosed in pediatric patients. In our study, hoarseness of voice was the most common clinical presentation.
The diagnosis of laryngeal papillomatosis is usually carried out by direct laryngoscopy or fiber-optic nasopharyngolaryngoscopy. Bronchoscopy can be performed to find any lesions at the tracheobronchial tree below the larynx. The appearance of the papillomas in the larynx looks like polypoidal mass with smooth surface and is confined to the larynx. Histopathologic examination of the mass gives definite diagnosis of the laryngeal papillomatosis. All cases of this study were confirmed by histopathologic examination. Helical computed tomography (CT) scan is the ideal imaging for the evaluation of laryngeal papillomatosis and the assessment of laryngotracheal airway. Other than CT scan, bronchoscopy (virtual) is another option for visualizing the airway on three-dimensional images.
The mainstay of treatment is surgical debulking, although no definite option for treating laryngeal papillomatosis is available. The aim of treating laryngeal papillomatosis is to excise the papillomas and restore the safe and patent airway with minimal injury to the 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 it is often impossible to achieve normal voice. Of 21 cases in this study, 10 patients underwent treatment by coblation technique. Coblation is a minimally invasive low heat method, which delivers a plasma layer for the dissolution of the target tissues. The wands of coblation are designed to function at 40°C–70°C to minimize heating, charring, or burning. Powered instrument such as a microdebrider is now the gold standard technique for the excision of the laryngeal papillomas. A non-serrated laryngeal blade is usually used with a setting of 300–700rpm, which makes papillomas to be suctioned into the debrider with minimal trauma to the surrounding normal tissues. The laryngeal blades help in comprehensive and gentle excision of papillomas with minimal involvement of the lower airway. Use of endoscope makes it more precise with minimal damage to the mucosa. There is no thermal trauma to the surrounding tissues. One study showed that the excision of the papillomatous lesion from the larynx has better disease clearance with shorter duration of procedure and minimal postoperative pain in comparison to the CO2 laser. CO2 or Potassium titanyl phosphate laser has been used for debulking of laryngeal papillomas. However, laser causes thermocoagulation damage to the underlying laryngeal tissue of the child, 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 using microflap method. It reduces injury to the vocal fold along with disease clearance. In cold steel method, thermal damage to the adjacent tissues is also avoided. It has unmistakable impediment of having no hemostasis when evacuating a vascular injury. Nowadays, cold steel technique is not much successful. Surgery cannot prevent recurrence of the disease, so different adjuvant therapies are often provided to the patients., The complete removal of the lesions may lead to recurrences in many patients due to the presence of latent viruses. In pediatric patients, approximately five surgical procedures per year are needed to prevent recurrences. The type of surgical technique often decides the patient outcome. There is a high chance of recurrence or complications after surgery due to repeated manipulation of the larynx. There is increased chance of anterior glottic synechia which is a frequently encountered complication. The synechia at the anterior and posterior commissure also occurs in 0.8%–12% and 3.6%–11.9% of the study cases, respectively. Laryngeal or tracheal stenosis is seen in up to 14% of cases. Less commonly observed complications are granulations and laryngoceles. In this study, one case showed anterior commissure synechia, one showed glottic stenosis, and one showed posterior commissure synechia after treatment as surgical complications.
Adjuvant treatment can be classified into antiviral treatment and medications with antiproliferative or immunomodulatory properties. The adjuvant therapies such as interferon alpha (IFN-α), photodynamic therapy, acyclovir, ribavirin, indole-3-carbinol, cis-retinoic acid, cidofovir, and vaccines are usually costly to be adopted in Indian perspective.
Cidofovir is a cytosine nucleotide analogue, which specifically repress viral DNA polymerase during replication of the virus. In recurrent laryngeal papillomatosis, it may very well be administrated intravenously or through nebulization or by intralesional infusion. Adjuvant topical injection of cidofovir is useful for halfway or absolute relapse of the sores and to diminish the recurrence of careful treatment. Intralesional injection has an advantage of maintaining low plasma level so that toxicity will be minimized without any side effects.
IFN is one of the adjuvant medications used in laryngeal papillomatosis, which gives positive outcomes as far as illness advancement is concerned by causing decrease of the papilloma development. The side effect of the IFN when given in intravenous route leads to toxicity with a reversible ascent in serum transaminase level and a possibility for thrombocytopenia and leucopenia. Common side effects of IFN are fatigue, transient fever, nausea, arthralgia, headache, and infantile spastic diplegia. Presently, lesional application of IFN-α is tried but it needs further studies in patients with laryngeal papillomatosis. The development of newer vaccinesagainst HPV gives potential to control the disease by preventing the frequency of sickness and transmission of infection. The quadrivalent immunization is frequently given in anticipation of cervical and anogenital malignancies and pre-carcinogenetic sores due to HPV subtypes 6, 11, 16, and 18. Currently, HPV antibodies are not endorsed for the utilization in neonates, so they need further research. Tracheostomy might be required for inadequate of laryngeal airway, particularly when other interventions are failed. In contrast with HPV 6, contamination with HPV 11 has all the earmarks of being bound to bring about extensive laryngeal lesions with tracheostomy. When tracheostomy done in laryngeal papillomatosis, decannulation must be executed when laryngeal airway is satisfactory and disease is controlled as tracheostomy site gives an extra site to quick colonization of infectionandhelps in spread of the disease to distal airway., The diminishing frequency of cases in our setup stays unexplained with our constrained epidemiological information. The present convention for expanding vaccinations may conceivably be a couple of the significant components included. The present administration conventions for Indian patients are administered by the standards of the Western world. It might be conceivable to have racial, ethnical, and organic contrast in the nature of the laryngeal papillomatosis in the Indian subcontinent.
| Conclusion|| |
Laryngeal papillomatosis is a viral disease, and the clinical behavior of this lesion in pediatric age is unpredictable. The prognosis of this lesion is unpredictable due to its nature of recurrence. Nowadays, increasing immunization, better care during pregnancy, or judicious use of anti-infective agents may be useful for reducing laryngeal papillomas in clinical practice. Laryngeal papillomatosis in children with a history of surgeries often has aggressive nature of the disease. Very young children and children with tracheostomy tube should receive a strict follow-up in future. Coblators and microdebrider are ideal techniques for debulking laryngeal papillomatosis. However, the outcome of this study will definitely encourage future research work on laryngeal papillomatosis in pediatric patients.
Ethical policy and institutional review board statement
This study was approved by the institutional ethics committee with reference number IMS/IEC/57/2014.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We are thankful to the dean and medical superintendent of the Institute of Medical Sciences and SUM Hospital, Siksha “O” Anusandhan Deemed to be University, Bhubaneswar, Odisha, India, for supporting this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]