Practice Essentials
Recurrent respiratory papillomatosis (RRP) is a benign lesion of the larynx and trachea. It is caused by the human papillomavirus (HPV), which similarly causes warts often visible on the skin, especially on the hands. [1]
Recurrent respiratory papillomatosis (RRP) is most commonly observed in children, but it can occur in adults. Although lesions seem histologically and pathologically similar in children and adults, clinically they behave much differently. Children frequently require multiple surgical procedures, and their disease often becomes quiescent in adolescence. Adults with recurrent respiratory papillomatosis (RRP) usually require only a few surgical excisions for cure. The disease can be devastating for a child, however, occasionally necessitating up to 150 surgeries over the youngster's lifetime. Recurrent respiratory papillomatosis (RRP), which can progress to involve the lungs and transform into squamous cell carcinoma of the airway, is one of the most common causes of hoarseness and airway obstruction in children. [2]
Signs and symptoms of recurrent respiratory papillomatosis
Signs and symptoms of recurrent respiratory papillomatosis (RRP) include the following:
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Stridor usually begins as an inspiratory noise consistent with glottic or supraglottic disease but then becomes biphasic with progression of disease
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As the papilloma grows, the airway obstructive features worsen; other clinical presentations include cough, pneumonias, and dysphagia
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Aphonia or breathy voice suggests a larger glottic lesion
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A low-pitched, coarse, fluttering voice suggests a subglottic lesion
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Children with papillomas of the larynx do not usually become symptomatic before age 6 months
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Signs of severe airway obstruction include tachypnea, stridor, retractions (suprasternal, substernal, intracostal), flaring of the nasal ala, and use of accessory neck or chest muscles
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Increasing air hunger may cause the child to sit with the neck hyperextended in an attempt to improve airflow
Workup in recurrent respiratory papillomatosis
Laboratory studies for the disease do not exist, although biopsies of the papillomas themselves can be tested to determine the type of human papillomavirus (HPV) present.
If any papilloma is diagnosed on flexible fiberoptic nasopharyngoscopy, no imaging studies are necessary for initial diagnosis. For children with airway obstructive symptoms for which no lesion is observed in the glottic larynx, certain imaging studies can be obtained for diagnosis of airway obstructive lesions of the trachea.
The diagnostic procedure of choice for recurrent respiratory papillomatosis (RRP) is initial flexible laryngoscopy in the clinic. If this is not diagnostic, the secondary diagnostic procedure of choice is a rigid bronchoscopy in the operating room with biopsy of the lesion.
Management of recurrent respiratory papillomatosis
Excision by carbon dioxide laser is the most commonly employed lesion removal method. [3] Several medical therapies have been tried as adjuvant therapy for laryngeal recurrent respiratory papillomatosis (RRP). [4] The actual effectiveness of any reported medical therapy for the disease is difficult to determine because the underlying aggressiveness of the disorder is poorly understood.
History of the Procedure
Historically, recurrent respiratory papillomatosis (RRP) was believed to be a surgical disease only. However, because of its significant recurrence rate, various medications have been attempted over the last 2 decades with varying degrees of success. In 1990, human papillomavirus (HPV) was discovered as the etiologic agent responsible for papilloma in the larynx and trachea. Since this discovery, the disease mechanism has been extensively investigated, and new antivirals have been tested. International meetings devoted solely to HPV have been organized.
In 1995, the Centers for Disease Control and Prevention (CDC) created a recurrent respiratory papillomatosis (RRP) task force to learn more about the disease. Because recurrent respiratory papillomatosis (RRP) in children is rare and its clinical course hard to predict, the task force combined data from 20 institutions and children's hospitals around the country. The initial goal of the recurrent respiratory papillomatosis (RRP) task force was to diagnose the true incidence and prevalence of the disease because most medical centers have only 15-40 patients with recurrent respiratory papillomatosis (RRP), even in large metropolitan areas.
Once the epidemiology of the disease is established, then prospective medical and surgical therapy trials can be evaluated more thoroughly in large groups of patients. Today, despite these efforts, human papillomavirus (HPV) is still misdiagnosed as asthma, croup, or chronic bronchitis because they all display symptoms of airway obstruction. However, as the disease becomes better known, recurrent respiratory papillomatosis (RRP) diagnosis will be made more often.
Problem
Recurrent respiratory papillomatosis (RRP) is a wart on the laryngeal, tracheal, bronchial, or other respiratory mucosa caused by human papilloma virus (HPV), usually types 6 and 11.
Epidemiology
A study carried out in the United States by Amiling et al found that among 215 children with childhood-onset recurrent respiratory papillomatosis (RRP), vaginal delivery was performed in 191 cases (88.8%), with 138 of the patients (64.2%) being firstborn. [5]
Frequency
Based on a survey of otolaryngologists, 1500-2500 new cases of childhood-onset recurrent respiratory papillomatosis (RRP) are estimated to occur each year in the United States. Incidence among children in the United States is estimated at 4.3 cases per 100,000 persons. Adult incidence is estimated at 1.8 cases per 100,000 persons. (A study by Donne et al estimated the prevalence of patients with recurrent respiratory papillomatosis in the United Kingdom to be 1.42 per 100,000. [6] ) Roughly 15,000 surgical procedures for the condition are performed each year, at an estimated cost of $100 million.
Age
The distribution of cases of recurrent respiratory papillomatosis (RRP) is bimodal, with an initial peak in the childhood years and a second peak in the adult years in people aged 20-40 years. However, an international European study suggested that the age of onset for recurrent respiratory papillomatosis actually has three peaks, at 7, 35, and 64 years. [7] Childhood onset for recurrent respiratory papillomatosis (RRP) is more common and more aggressive than in adults. Most children with the disease appear to be the first born of young mothers and to come from families with low economic status.
Sex
In children, the male-to-female ratio is approximately equal. For adults, the male-to-female ratio may be 4:1.
Etiology
Human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Seventy types of human papillomaviruses (HPVs) have been identified. Human papillomavirus (HPV) types 6 and 11 cause benign papilloma in the airway and are responsible for genital warts. Human papillomavirus (HPV) types 16 and 18 have most often been associated with cancer in the genital area and upper aerodigestive tract in both children and adults. [8, 9, 10, 11]
In patients with laryngeal papilloma, normal mucosa has human papillomavirus (HPV) in 20% of cases. In otherwise normal airways, human papillomavirus (HPV) deoxyribonucleic acid (DNA) has been retrieved from laryngeal and tracheal mucosa in 4% of cases.
In the aforementioned study by Amiling et al, human papillomavirus (HPV) was detected in 157 of 162 specimens (96.9%) taken from the papillomas of children with childhood-onset recurrent respiratory papillomatosis (RRP). In 129 specimens (79.6%), only HPV type 6 was present, with 25 specimens (15.4%) having only HPV type 11. [5]
Pathophysiology
Childhood-onset recurrent respiratory papillomatosis
The precise mode of human papillomavirus (HPV) transmission is unclear. Most studies indicate that childhood-onset recurrent respiratory papillomatosis (CORRP) occurs during exposure of a child's upper aerodigestive tract to the cervix and vagina of a mother with genital human papillomavirus (HPV) infection during normal abdominal delivery. Why CORRP develops in only a few percent of children who are born abdominally to mothers with active genital condyloma is not well understood.
Statistics
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In 1998, Shah et al reported the risk of an abdominally delivered child contracting RRP from a mother who has active condylomatous lesions at approximately 1 in 400. [12]
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Fifty percent of mothers of affected children had active or previous condylomata.
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Human papillomavirus (HPV) was recovered on nasopharyngeal swab from a third of infants born to mothers with active uterine human papillomavirus (HPV).
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In the United States, 1 million cases of genital papilloma per year manifested as condyloma acuminatum involving the cervix, vulva, penis, or other anogenital sites.
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Clinically apparent human papillomavirus (HPV) infection has been noted in 1.5-5% of pregnant women in the United States. Human papillomavirus (HPV) has been recovered in up to 20% of disease-free mucosa in the anogenital area of pregnant women.
Factors possibly contributing to development of HPV
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Status of the child's immune system
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Length of time in the birth canal
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Volume of virus in the birth canal
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Abdominal delivery: One case reports a child born by cesarean delivery (with no premature ruptured membrane) who developed recurrent respiratory papillomatosis (RRP), casting doubt on the birth canal theory.
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Presence of local trauma
Adult-onset recurrent respiratory papillomatosis
For adult-onset recurrent respiratory papillomatosis (AORRP), oroanal or orogenital contact is considered a possible mode of virus transmission versus a latent virus becoming active. Ten percent of sexually active men and women with no clinical evidence of disease have human papillomavirus (HPV) identified in the penis or cervix by Southern blot hybridization analysis, suggesting presence of latent infection.
Virus mechanisms
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Once transmitted to the airway, human papillomavirus (HPV) establishes itself in the basal layer of the mucosa, where viral DNA enters the cell and produces ribonucleic acid (RNA) to produce viral proteins, similar to the replication mechanism of other viruses. This action incites the transformation of the mucosa to papilloma formation.
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In 1993, Kashima et al reported an increased risk of papilloma in the airway at sites of squamous epithelium or squamous metaplasia. [13]
Presentation
Childhood-onset recurrent respiratory papillomatosis
Children with CORRP usually present when aged 2-3 years with hoarseness, stridor, or airway obstruction. Papilloma has been reported to manifest as early as the first day of life or as late as the octogenarian years.
Symptoms and signs
See the list below:
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Stridor usually begins as an inspiratory noise consistent with glottic or supraglottic disease but then becomes biphasic with progression of disease.
-
As the papilloma grows, the airway obstructive features worsen. Other clinical presentations include cough, pneumonias, and dysphagia. Children are often misdiagnosed with asthma, croup, allergies, vocal nodules, or bronchitis. Recurrent respiratory papillomatosis (RRP) is misdiagnosed because of its rarity and the slowly progressive nature of the disease. Hoarseness without airway obstruction may indicate the small lesion.
-
Aphonia or breathy voice suggests a larger glottic lesion.
-
A low-pitched, coarse, fluttering voice suggests a subglottic lesion.
-
Children with papillomas of the larynx do not usually become symptomatic before age 6 months.
-
Document the quality of the voice on physical examination.
-
Signs of severe airway obstruction include tachypnea, stridor, retractions (suprasternal, substernal, intracostal), flaring of the nasal ala, and use of accessory neck or chest muscles.
-
Increasing air hunger may cause the child to sit with the neck hyperextended in an attempt to improve airflow.
-
All children with any of the signs of stable airway obstruction or voice disturbances must have a flexible fiberoptic nasopharyngoscopy in clinic.
Indications
Indications for surgery in recurrent respiratory papillomatosis (RRP) are based on the presence or absence of a lesion that causes symptoms. Laryngeal lesions, if present, usually cause symptoms and must be removed or treated. In a patient undergoing multiple surgeries a year, a lesion may only need to be removed because it is symptomatic and not necessarily every lesion needs to be removed in every surgical procedure. Surgical excision is the current standard of care in the treatment of recurrent respiratory papillomatosis (RRP). Adjuvant medical therapy has been investigated over the past 2 decades and continues to this day.
If the child or adult has only hoarseness, surgery can be scheduled as an elective procedure. If the child or adult has airway obstruction, immediately treat it as an emergency procedure.
Relevant Anatomy
During surgical removal, use caution to spare all vital structures and to prevent iatrogenic scarring of the larynx or trachea.
Up to 30% of patients who have had surgical excision of papilloma in the anterior commissure of the larynx have developed anterior glottic scarring and web formation. Unless the surgeon can be assured that iatrogenic injury will not result from their technique, papilloma should be left in the anterior commissure in children requiring several surgeries a year.
A small percentage of patients have developed subglottic stenosis from repeated surgical excisions at the anterior commissure of the larynx.
Avoid tracheotomy at almost all cost. Frequent surgical excision (ie, as often as once per 2 wk) is preferable to tracheotomy for children or adults who have recurrent aggressive disease. Tracheotomy is believed to induce spread of the papilloma down the trachea and into the bronchi and lungs.
Contraindications
No contraindications to surgical removal of recurrent respiratory papillomatosis (RRP) exist.
