Tracheal Papillomatosis

Tracheal papillomatosis is the extension of human papillomavirus induced squamous papillomas from the larynx into the trachea and sometimes the bronchi and lung parenchyma. It represents the lower airway form of recurrent respiratory papillomatosis, and it carries a much greater morbidity than disease confined to the larynx.

• Causative agents are HPV types 6 and 11. Type 11 is associated with more aggressive disease, earlier onset, and a higher rate of tracheal and pulmonary spread.
• Tracheal involvement occurs in about 5 to 17 percent of patients with laryngeal disease. Pulmonary parenchymal spread is rarer (about 1 percent) and often follows prolonged disease, repeated instrumentation, or tracheostomy.
• Risk factors for tracheobronchial spread: juvenile onset (especially before 3 years of age), HPV 11, tracheostomy (strongest, seeding at the stoma and trachea), frequent endoscopic procedures, and extensive laryngeal disease.
• Pulmonary papillomas can cavitate and become necrotic. Malignant transformation to squamous cell carcinoma is a risk in lung disease (about 3 to 7 percent), more so with smoking or prior radiation.

• Chronic cough, wheeze, and exertional dyspnoea that mimic asthma or bronchitis and do not respond to bronchodilators.
• Stridor (when tracheal lesions are large), and progressive airway obstruction.
• Recurrent pneumonia, atelectasis, lobar collapse, or lung abscess when distal bronchi are involved.
• Haemoptysis, chest pain, and weight loss in advanced disease or malignant change.
• Hoarseness is present because of coexisting laryngeal disease.
• Children may show failure to thrive, tachypnoea, and respiratory distress.

• Flexible or rigid bronchoscopy shows multiple pink, exophytic, wart like or cauliflower lesions on the tracheal wall (often anterior and posterior walls, carina, and bronchi). Bronchoscopy must be done carefully because bleeding can obscure view and sedation can precipitate airway obstruction.
• Biopsy and histology: fibrovascular cores covered by non-keratinising squamous epithelium with koilocytosis. HPV typing by PCR confirms types 6 and 11 and identifies high risk types (16, 18) if dysplasia is present.
• CT of the chest: tracheal and bronchial wall nodules and, in pulmonary disease, multiple solid or cavitating nodules, predominantly in the dependent lung zones, with thick walled cavities and air fluid levels. Differential diagnosis includes septic emboli, granulomatosis with polyangiitis, metastases, and tuberculosis.
• Chest radiograph may show nodules, atelectasis, or cavities.
• Spirometry and flow volume loops: variable or fixed intrathoracic obstruction.
• Any enlarging, necrotic, or solid pulmonary lesion needs biopsy to exclude carcinoma.
• Document severity using a numerical anatomical scoring of airway sites to monitor response and to guide treatment frequency.

• Surgical debulking is the foundation, with the goals of airway patency and preservation of normal mucosa:
  • Bronchoscopic removal with microdebrider, cold forceps, or CO2 or KTP laser (with minimum power and short pulses to limit thermal injury and stenosis). Procedure intervals are guided by symptoms and endoscopic findings, usually every 4 to 12 weeks initially.
  • Avoid tracheostomy whenever possible because it seeds the distal airway; if required for severe obstruction, remove it as soon as possible.
  • Ventilation during surgery using jet ventilation or a spontaneous ventilation technique with great care, as papilloma fragments can be aspirated distally.
• Adjuvant therapy is indicated when more than 4 procedures a year are needed, regrowth is rapid, there is distal spread, or airway compromise persists:
  • Intralesional cidofovir 5 mg/mL (0.5 to 1 mL per site) injected into the base of the lesion after debulking, repeated every 2 to 4 weeks for 4 to 6 injections. Monitor renal function if systemic absorption is possible; the risk of dysplasia has been raised in some reports.
  • Bevacizumab: intralesional 5 mg/mL (maximum about 1 mL per site at 0.5 to 1 mg/kg total) or systemic 5 mg/kg to 10 mg/kg intravenously every 2 to 4 weeks, often the preferred agent in aggressive pulmonary disease. Monitor blood pressure and urine protein; stop for bleeding or poor wound healing.
  • Interferon alfa-2b 3 million units/m2 subcutaneously daily for 28 days then three times weekly, limited by fever, flu like symptoms, and bone marrow suppression, now seldom used.
  • Other adjuncts: indole-3-carbinol 200 mg to 400 mg orally daily, celecoxib, mumps vaccine injection, and aciclovir (limited evidence).
  • HPV vaccination (9-valent, 0.5 mL intramuscularly at 0, 2, and 6 months) as an adjuvant has been associated with longer intervals between procedures in recent series.
• Pulmonary disease: serial endoscopic resection of accessible lesions, systemic bevacizumab, and lobectomy only for localised disease with complications. Immunotherapy (PD-1 blockade) is under investigation in refractory disease.
• Reflux treatment: omeprazole 20 mg to 40 mg daily to reduce mucosal irritation.
• Surveillance: bronchoscopy at regular intervals, CT of the chest annually for patients with pulmonary spread or smoking history, and low threshold for biopsy of changing lesions. Counsel against smoking.
• Complications: airway stenosis, tracheal scarring, respiratory failure, pulmonary cavitation, bronchiectasis, and malignant transformation. Prognosis is guarded in pulmonary disease.