Recurrent Tracheobronchial Papillomatosis with Pulmonary Involvement due to HPV Types 6 and 11

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Recurrent Tracheobronchial Papillomatosis with Pulmonary Involvement due to HPV Types 6 and 11

Introduction

Recurrent tracheobronchial papillomatosis with pulmonary involvement is a rare but serious manifestation of juvenile recurrent respiratory papillomatosis (JORRP) caused by HPV 6 and HPV 11. Integrating CT imaging correlation, viral genotype analysis, and clinical management, this case reflects the potential for lower airway and lung disease in HPV 6/11 infection, often underestimated.

Drawing upon the case report “17-year-old male with juvenile recurrent respiratory papillomatosis” from Applied Radiology (July 2011), this case exemplifies disease progression from cervical/tracheal papillomas to pulmonary cavitary lesions, nodules, and bronchial obstruction, despite prior surgical and antiviral (cidofovir) therapy

1. Clinical Background

A 17‑year‑old male with a long history of juvenile‑onset RRP began experiencing exacerbation of cough and dyspnea, despite multiple laser resections and intravenous cidofovir. Notably, he developed mediastinal and right hilar lymphadenopathy, biopsied to reveal reactive follicular hyperplasia, without malignancy

JORRP is caused by HPV types 6 and 11, with type 11 often associated with more aggressive disease and distal airway involvement. Global incidence estimates are approximately 4 per 100,000 in children and 2 per 100,000 in adults, with pulmonary spread occurring in fewer than 1–5% of cases

2. Imaging Findings

A CT scan was performed using a Somatom Definition AS 64 scanner (Siemens, Erlangen, Germany). The CT scan revealed multiple polypoid masses protruding into the tracheal lumen, consistent with tracheal papillomatosis (Figure 1). The largest lesion measured approximately 6 mm. The CT scan revealed a 5.0 x 3.0 cm mass in the inferior aspect of the right hilum, with consolidation in the right lower lobe distal to the mass, suggesting obstructive pneumonia (Figure 2). In addition, multiple cavitary lesions with thick, irregular walls and multiple nodules were observed in both lungs (Figures 3 and 4).


3. Pathophysiology & HPV Genotype Correlation

HPV‑6 and HPV‑11 are considered low‑risk genotypes, yet HPV‑11 is consistently implicated in more severe and distal disease, including tracheobronchial and pulmonary spread. A systematic review found that among RRP patients with pulmonary involvement, approximately 21% were HPV‑11 positive, with overall HPV‑6/11 positivity in RRP exceeding 90%. Transmitted typically via vertical passage through the birth canal, children with JORRP often present early (ages 2–6) and are at higher risk of aggressive recurrence, multiple surgeries, and airway compromise.

4. Diagnostic Imaging & Differential

·         Chest radiography may reveal solid or cavitary nodules, but CT provides superior lesion characterization, extent, and planning for bronchoscopy or resection

·         CT hallmark features:

o    Tracheal/bronchial sessile or polypoid masses

o    Solid nodules or cystic cavities in lung parenchyma

o    Variable wall thickness: thick/irregular or almost imperceptible

o    Bronchiectasis, atelectasis or post‑obstructive changes

o    Enlarged lymph nodes: suspicious for malignancy, though reactive hyperplasia may be benign

5. Clinical Course & Treatment

Despite multiple surgical excisions and intravenous cidofovir, the adolescent progressed to mediastinal lymphadenopathy and extensive pulmonary disease. Serial MDCT surveillance was essential due to risk of malignant transformation into squamous cell carcinoma, reported in 2–3% of RRP cases (particularly with HPV‑16/18, smoking, or radiation exposure)

Primary management includes repeat surgical debulking (laser or microdebrider), with adjuvant therapies reserved for severe disease (>4 procedures/year, distal spread, or rapid recurrence):

·         Antivirals: intralesional or intravenous cidofovir

·         Bevacizumab (anti‑VEGF monoclonal antibody) – systemic or intralesional, showing promising efficacy in reducing recurrence and progression in severe JORRP with pulmonary involvement

The case underscores the importance of HPV vaccination, which has significantly reduced juvenile RRP incidence in populations with high uptake (e.g., USA, Australia)

6. Expert Commentary & Recommendations

From a global expert viewpoint:

·         Early diagnosis and routine CT monitoring are vital in JORRP with suspected pulmonary spread.

·         HPV genotyping (particularly identifying HPV‑11) may help stratify risk for distal spread.

·         Use of systemic bevacizumab may be considered in refractory or pulmonary‑involved cases, although long‑term maintenance and cost remain challenges

·         HPV vaccination (quadrivalent or nonavalent) remains the most powerful preventive measure for juvenile RRP by targeting HPV‑6 and HPV‑11

Quiz

1.       On CT imaging, what is the primary distinguishing characteristic of pulmonary involvement by HPV in RRP?
A. Homogeneous ground‑glass opacity
B. Multiple solid and cavitary nodules with variable wall thickness
C. Pleural effusion with lymphadenopathy
D. Miliary nodules

2.  HPV type most commonly associated with more aggressive and distal pulmonary spread in juvenile RRP?
A. HPV‑6
B. HPV‑11
C. HPV‑16
D. HPV‑18

3. Which adjuvant therapy has shown promise in severe juvenile RRP with pulmonary involvement, especially when surgical options are limited?
A. Systemic interferon‑α
B. Intralesional ribavirin
C. Systemic bevacizumab
D. Photodynamic therapy

Answer & Explanation

1. Answer: B. Explanation: Pulmonary HPV papillomatosis typically presents on CT as multiple solid and cystic nodules, with thick or thin walls depending on necrosis and growth stage

2. Answer: B. Explanation: Although both HPV‑6 and HPV‑11 cause RRP, HPV‑11 is correlated with more aggressive disease and has a higher frequency of pulmonary involvement.

3. Answer: C. Explanation: Systemic bevacizumab, an anti-VEGF monoclonal antibody, has demonstrated efficacy in reducing disease burden and delaying recurrence in severe RRP, particularly for pulmonary involvement


7. Conclusion

This case of recurrent tracheobronchial papillomatosis with pulmonary involvement due to HPV‑6 and HPV‑11 encapsulates the spectrum of juvenile RRP progression—from tracheal papillomas, lymphadenopathy, to cavitary lung lesions and nodules. CT imaging is indispensable for detection and follow‑up. High‑risk HPV genotypes, especially HPV‑11, mark a more aggressive disease course. While surgery remains first‑line, adjuvant antivirals and anti‑angiogenic therapy (bevacizumab) are increasingly important for severe, distal disease. Ultimately, HPV vaccination is key to prevention. 

References

[1] D. Koujah, R. B. Towbin, C. M. Schaefer, and A. J. Towbin, “Recurrent Respiratory Papillomatosis,” Applied Radiology, vol. 5, pp. 7–9, Oct. 2024. appliedradiology.com
[2] I. Sechi et al., “Pulmonary Involvement in Recurrent Respiratory Papillomatosis: a Systematic Review,” Infectious Disease Reports, vol. 16, no. 2, pp. 200–215, Feb. 2024. MDPI+1appliedradiology.com+1
[3] R. Ruiz and K. B. Zur, “Recurrent Respiratory Papillomatosis,” Current Otorhinolaryngology Reports, vol. 9, pp. 23–28, Feb. 2021. 스프링거링크
[4] S. Muresu et al., “Juvenile-onset recurrent respiratory papillomatosis: What do we know in 2024,” SciDirect, Jan. 2024. Taylor & Francis Online+5ScienceDirect+5MDPI+5
[5] D. A. Larson and C. S. Derkay, “Epidemiology of recurrent respiratory papillomatosis,” APMIS, vol. 118, pp. 450–454, 2010. actascientific.com+5appliedradiology.com+5ScienceDirect+5
[6] S. S. Kramer, W. D. Wehunt, J. T. Stocker, and H. Kashima, “Pulmonary manifestations of juvenile laryngotracheal papillomatosis,” AJR American Journal of Roentgenology, vol. 144, pp. 687–692, 1985. appliedradiology.com
[7] J. S. Prince, D. R. Duhamel, D. L. Levin, et al., “Nonneoplastic lesions of the tracheobronchial wall: Radiologic findings with bronchoscopic correlation,” Radiographics, vol. 22, pp. S215–S230, 2002.

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