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© Borgis - New Medicine 2/2002, s. 64-66
Lidia Zawadzka-Głos, Mieczysław Chmielik, Anna Bielicka
Laryngeal papillomatosis in children and their surgical treatment
Department of Paediatric Otorhinolaryngology, The Medical University of Warsaw, Poland
Head: prof. Mieczysław Chmielik M.D.
Summary
Laryngeal papillomas in children constitute a disease of viral aetiology caused by Human Papilloma Virus. Even though the changes are histologically benign, their exophytic growth may lead to a critical airway obstruction and the child´s suffocation. Due to the tendency to recur, lack of causal treatment, and risk of malignancy the optimal method of treating this condition is still being sought. The study presents methods applied nowadays in the treatment of laryngeal papillomas; especially, it concentrates on a classical papillotomy and its main advantage: the diminished risk of scar formation leading to laryngeal stenosis and vocal fold injury with speech disorders.
Recurrent respiratory papillomatosis in children is a disease of viral origin which is caused by human papillomavirus (HPV). In cases of respiratory papillomatosis types 6 and 11 (HPV 6 and HPV 11) (1, 2) are met most frequently. These same types are responsible for condyloma acuminata in women. The most common type of virus in children with tracheal and bronchial papilloma is HPV 11.
To identify the type of HPV the polymerase chain reaction (PCR), in situ hybridization, or southern blotting hybridization are used. Subtypes of HPV should be estimated at the onset of disease and at any change in the clinical course, particularly if the frequency of recurrence has increased or if papilloma has affected the lower levels of the respiratory tract.
Recurrent respiratory papillomatosis may affect children of any age; a diagnosis usually being made between 2 and 3 years of age, and below 5 years of age in 75% of small patients (3). The incidence of laryngeal papillomatosis in west European countries is about 0.6-4.0 per 100 000 children (4, 5).
The precise mode of HPV transmission remains unclear. Because the same subtypes of HPV are responsible for genital HPV infections in women and juvenile laryngeal papillomatosis, some authors have tried to find an association between maternal condylomata and the development of papilloma in the child. It is assumed that HPV infection may be passed by vertical transmission from mother to child during pregnancy via the placenta or ascending from the birth canal. In the perinatal period the most likely method of maternal-foetal HPV transmission is through direct contact in the birth canal. However, no studies have shown unequivocal confirmation that children born from a mother with condyloma acuminata are more liable to laryngeal papillomatosis. Also, it has not been proved that caesarean section or removal of viral condylomata before delivery reduce the risk of transmission of HPV infection (6). Shah et al. estimated that the risk of a child contracting the disease from a mother who has an active condylomatous lesion and delivers vaginally is only about 1 in 400 children (7).
The most common location of respiratory papillomatosis is the larynx, especially those regions which adjoin stratified squamous epithelium and ciliated epithelium. These are the vestibulum of the larynx, vocal cords, and the subglottal area. Papillomata may appear on the soft palate, in the laryngeal pharynx, in the oesophagus and in the vestibule of the nose. If laryngeal papillomatosis grows more intense the papillomatous changes may affect the trachea, or the main and segmental bronchi.
Papilloma consist of a rich vascularized connective tissue stroma, covered by non-keratinized stratified squamous epithelium. Papillomata are exophytic, irregular pinkish nodes growing up direct from the mucosa or having a petiole. Usually they grow multifocally, and have a tendency to recurrence.
The first symptom of laryngeal papillomatosis most frequently is progressive hoarseness. Other symptoms presenting in children with papillomatosis may be: stridor, beginning as an inspiratory noise and becoming biphasic with progression of the disease, haw, chronic cough, recurrent pneumonia, dysphagia, and dyspnoea. The duration of symptoms before diagnosis varies. Dyspnoea increases gradually, at first as effort dyspnea, but when the lumen of the respiratory tract becomes narrower dyspnoea may appear during rest. If the petiolate papilloma wedges in the vocal cords the dyspnoea has an acute character.
Juvenile laryngeal papillomatosis may persist to the age of maturity. In these cases there is an increased risk of malignant transformation into squamous cell carcinoma. Sommers et al. suggest that age of onset and specific viral subtypes may be correlated with severity of the disease and the clinical course. Children infected with HPV 11 appear to have a more obstructed airway course early in the disease, and a greater need for tracheotomy (8).
Till now no single method has been found to be totally effective in the eradication of juvenile laryngeal papillomatosis. In the Department of Paediatric Otolaryngology in Warsaw the main method of treatment in these cases is classical papillotomy using the Kleinsasser arrangement. The main goal of treatment is complete removal of the papillomas, and conservation of the anatomical and phnation functions of the larynx. Tracheotomy is a procedure to be avoided unless absolutely necessary, because tracheotomy may activate or spread the disease lower in the respiratory tract or in the region of the tracheostoma.
Intralaryngeal microsurgery is routine nowadays in the diagnosis and treatment of laryngeal diseases. It is a relatively light invasive method, and allows precise operations in the larynx. In paediatric laryngology especially intralaryngeal microsurgery has wide application. Because indirect laryngoscopy is impossible in small children, direct laryngoscopy is the main method of visualisation of the intralaryngeal structures. In many cases, for example in laryngeal papillomatosis, it is the beginning of treatment.
The classical papillotomy is performed under general anaesthesia with intralaryngeal intubation. An introduced laryngoscope is immobilized with thoracic support, leaning directly on the thorax or, in the case of infants and small children, on a support fixed to the operating table. In children instruments with a length of 18 centimetres are used. The ends of forceps and scissors are straight, or may be bent up or to one side. One advantage of classical papillotomy is that the surgeon using precision instruments may easily distinguish between the brittle tissue of a papilloma and the mucosa of the vocal cords. The vocal cords are a very susceptibile organ and an operation performed in the larynx must preserve their tissue. The use of forceps gives a smaller risk of voice and breathing impairment leading to cicatrisation and intratracheal webs than the use of a laser. This is especially important in infants and small children in whom all surgical intervention in the larynx may lead to these lesions. In the Department of Paediatric Otolaryngology in Warsaw, in children below 10 years of age, a classical papillotomy is the only method used for surgical treatment of laryngeal papillomatosis. In the perioperative period steroids and antibiotics are not routinely used. In cases, where papillomata affect the lower levels of the respiratory tract the operation is extended by tracheobronchoscopy at the first stage. After removal of papilloma from the trachea and bronchi, intratracheal intubation is performed and in typical cases a papillotomy is carried out. A very difficult problem is treatment of papilloma of the small segmental bronchi.
The alternative procedure for surgical treatment of laryngeal papilloma in many laryngological centres is the use of a carbon dioxide laser. Because of life-threatening complications which may appear during this procedure, it is necessary to have considerable experience on the part of the surgeon, and appropriate training of the nursing staff. Complications after using a CO2 laser include pneumothorax or subcutaneous emphysema and the ignition of the intubation tube caused by laser. Although the incidence of life-threatening complications is low (< 0.5%), the occurrence of minor complications such as persistent laryngeal oedema, dysphagia, vocal cord fibrosis, or anterior glottic webs is relatively high. Later complications may include strictures of the larynx in the glottic or subglottic area.
In laryngological literature we find information about the use of the argon laser in the treatment of laryngeal papillomatosis. Laryngeal papillomas are a rich vascularized lesion. During classical papillotomy the surgical area is bleeding and precise ´´plucking out´´ of papillomata is time-consuming, and increases the possibility of spreading disease lower in the respiratory tract. Laser use gives the possibility of surgery in a dry area, but excessive tissue penetration may be complicated by laryngeal wall perforation and permanent vocal cord impairment, especially in a small child. A method which allows to operate in a dry area and allows the removal of laryngeal papillomatosis without healthy tissue impairment is argon plasma coagulation (APC). During an operation on bleeding papillomata the process of coagulation is suspended when the laser reaches a deeper drier layer in which the resistance value is critical and the work of the appliance must be intermittent. An advantage of APC is the lack of tissue carbonization, controlled depth of the coagulated layer avoiding the possibility of laryngeal and tracheal wall perforation, and a low risk of papillomatous lesion transference (a method without contact). APC gives the possibility of destroying papillomatosis stroma and thus the destruction of latent HPV virus in the mucous membrane. It may be a cause of reduction of disease recurrence.
In cases of frequent recurrence of papillomatosis, requiring surgical treatment many times per year, the same authors recommend combining surgical and pharmacological treatment. The most commonly recommended adjuvant therapy is alpha-interferon. Alpha interferon modulates the immune response by increasing production of a protein kinase and endonuclease which inhibit viral protein synthesis. In some patients alpha-interferon diminishes the dynamics of papilloma growth and frequency of recurrence. Clinical remissions after using alpha-interferon have also been observed (9). Satio and al. recognise that a combination of CO2 laser surgery and alpha-interferon is a powerful therapy for laryngeal papillomatosis (10). However, in some patients there are no improvements even after 12 months of treatment with interferon. Interferon therapy has side effects such as headaches, fever, arthralgia, myalgias, elevation of liver transaminase levels, leucopenia, and febrile convulsions.
In the pharmacological treatment of respiratory papillomatosis Acyclovir, Ribavirin, Isoprinosin, Podophyllinum, hormones, and Metotrexat have been used. Any of these drugs have a wider application in the treatment of this disease.
Recently, photodynamic therapy has been tested in the treatment of larygeal papillomatosis in some laryngological centres. This method is based on the transfer of energy to a light-sensitive drug. The original drug used was dihaematoporphyrin, which has a tendency to concentrate within papillomas to a greater degree than in the surrounding normal tissue. Before photoactivation with an argon laser, patients receive dihaematoporphyrin intravenously. Resarch has shown a statistically significant decrease in papillomatosis growth after using photodynamic therapy.
CONCLUSION
Many studies have been made into the treatment of laryngeal papillomatosis. Many surgical and pharmacological methods have been tested against this disease. Independent of the method of treatment, recurrence of papilloma has been seen. No therapy has been proved totally effective, and prognosis depends on the age of onset, type of HPV, clinical course of the disease, and involvement of the lower levels of the respiratory tract. Surgical treatment is not sufficient. According to many authors an improvement in the immunological response and causal treatment of papillomatosis as a viral infection, combined with surgical treatment, may guarantee successful treatment (11, 12, 13).
Piśmiennictwo
1. Mounts P. et al.: Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx. Proc. Natl. Acad. Sci. USA 1982, 79: 5425-5429. 2. Gissman H. et al.: Human papilloma virus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancer. Proc. Natl. Acad. Sci. USA 1983, 50:560-563. 3. Cripe T.P.: Human papillomavirus: Pediatric perspectives on a family of multifaceted tumorigenic pathogens. Pediatr. Inf. Dis. J. 1990, 9:839-844. 4. Bomholt A.: Juvenile laryngeal papillomatosis: An epidemiological study from the Copenhagen region. Acta. Otolaryngol. (Stochh) 1988, 105:367-371. 5. Lindeberg H., Elbrond O.: laryngeal papillomas: The epidemiology in a Danish sub-population 1965-1984. Clin. Otolaryngol. 1991, 15:125-131. 6. Smith E.M. et al.: Perinatal vertical transmission of human papillomavirus and subsequent development of respiratory tract papillomatosis. Ann. Otol. Rhinol. Laryngol. 1991, 100:479-483. 7. Shah K. et al.: Rarity of caesarean delivery in cases of juvenil onset respiratory papillomatosis. Obstet. Gynecol. 1986, 68:795-799. 8. Somers G.R. et al.: Juvenile laryngeal papillomatosis in a pediatric population: a clinicopathologic study. Pediatr. Pathol. Lab. Med. 1977 Jan-Feb, 17 (1):53-64. 9. Lusk R.P. et al.: Three-year experience of treating recurrent respiratory papilloma with interferon. Ann. Otol. Rhinol. Laryngol. 1987 Mar-Apr, 96 (2 Pt 1):158-62. 10. Satio R. et al.: Treatment of juvenile laryngeal papilloma with combination of laser surgery and interferon. Auris Nasus Larynx 1985, 12 (2):117-24. 11. Snowden RT. et al.: The predictive value of serum interleukine in recurrent respiratory papillomatosis – a preliminary study. Laryngoscope 2001 Mar, 111 (3):404-8. 12. Bonagura VR. et al.: Recurrent respiratory papillomatosis altered CD8 (+) T-cell subsets and T(H) 1/T(H) 2 cytokine imbalance. Clin. Immunol 1999 Dec, 93 (3):302-11. 13. Swygert C.: Human papillomatosis: disease and laboratory diagnosis. Br. J. Biomed. Sci. 1997 Dec, 54 (4):299-303. 14. Bergler W.: Treatment of recurrent respiratory papillomatosis with argon plasma coagulation. The Jour. of Laryng. and Otology. 1997, Vol 111:381. 15. Bergler W. et al.: The treatment of juvenile laryngeal papillomatosis with argon plasma coagulation. Dtsch Med. Wochenschr 1997, Aug 22, 122 (34-35):1033-6. 16. Craig S., Derkay M.D.: Recurrent respiratory papillomatosis. Laryngoscope 2001, 111:57-69. 17. Chmielik M.: Otorynolaryngologia dziecięca. Warszawa, PZWL 2001.
New Medicine 2/2002
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