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Torres-Canchala, L.;  Cleves-Luna, D.;  Arias-Valderrama, O.;  Candelo, E.;  Guerra, M.A.;  Pachajoa, H.;  Olaya, M. Systemic Bevacizumab for Recurrent Respiratory Papillomatosis. Encyclopedia. Available online: https://encyclopedia.pub/entry/41003 (accessed on 05 December 2025).
Torres-Canchala L,  Cleves-Luna D,  Arias-Valderrama O,  Candelo E,  Guerra MA,  Pachajoa H, et al. Systemic Bevacizumab for Recurrent Respiratory Papillomatosis. Encyclopedia. Available at: https://encyclopedia.pub/entry/41003. Accessed December 05, 2025.
Torres-Canchala, Laura, Daniela Cleves-Luna, Oriana Arias-Valderrama, Estephania Candelo, María Angelica Guerra, Harry Pachajoa, Manuela Olaya. "Systemic Bevacizumab for Recurrent Respiratory Papillomatosis" Encyclopedia, https://encyclopedia.pub/entry/41003 (accessed December 05, 2025).
Torres-Canchala, L.,  Cleves-Luna, D.,  Arias-Valderrama, O.,  Candelo, E.,  Guerra, M.A.,  Pachajoa, H., & Olaya, M. (2023, February 08). Systemic Bevacizumab for Recurrent Respiratory Papillomatosis. In Encyclopedia. https://encyclopedia.pub/entry/41003
Torres-Canchala, Laura, et al. "Systemic Bevacizumab for Recurrent Respiratory Papillomatosis." Encyclopedia. Web. 08 February, 2023.
Systemic Bevacizumab for Recurrent Respiratory Papillomatosis
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This entry is adapted from the peer-reviewed paper 10.3390/children10010054

Respiratory recurrent papillomatosis (RRP) is a fatal disease with no known cure. In severe RRP cases, systemic bevacizumab (SB) could be used as adjuvant therapy. SB may be a promissory treatment and control option for RRP. More research is needed to evaluate the efficiency and adverse effects in various populations.

adjuvant therapy child adult adult-onset recurrent respiratory papillomatosis juvenile-onset papillomatosis

1. Introduction

Recurrent respiratory papillomatosis (RRP) and recurrent cutaneous papillomatosis (RCP) are devastating diseases with a high risk of long-term complications that impact patients’ and their families’ quality of life. The juvenile-onset RRP (JO-RRP) incidence rate is 4.3 per 100,000, whereas the adult-onset RRP (AO-RRP) incidence rate is 1.8 per 100,000 [1]. The two types of human papillomavirus (HPV) that cause RRP and RCP are HPV 6 and HPV 11. RRP and RCP are distinguished by the recurring growth of papillomas in the respiratory and gastrointestinal tracts, which can obstruct them in severe cases. There is no treatment for systemic papillomatosis [2].
Extra laryngeal papillomatosis has been seen in up to 30% of cases, with the oral cavity, trachea, and bronchi being the most common sites [3][4]. These patients have recurrent bronchiectasis, pneumonia, and decreased lung function [3][4].

2. Systemic Bevacizumab Studies

Table 1 summarizes the clinical characteristics of patients with RRP before SB treatment. The studies included were published between 2009 and 2021. A total of 34 patients were described in these studies from the United States (three case reports; n = 3, four case series; n = 12), India (one case report; n = 1), Germany (one case report; n = 1, one case series; n = 5), Colombia (one case series; n = 3), Argentina (one case report; n = 1), Chile (one case report; n = 1), and Spain (one case series; n = 2). In total, In total, 17 and 34 patients were under 18 years old and were adults, respectively. The median age for those under 18 years old was 8 yr (min = 0.58 and max = 16), and the median for adults was 34 years (min = 18 and max = 87). There were 23 males (67.6%).
Table 1. Clinical characteristics of patients with RRP prior systemic bevacizumab treatment. CR, Complete Regression, PR, Partial Regression, VGPR, very good partial remission, NA Not Applicable.
Study Author Country Year Age at Treatment Start Gender Age at Onset Larynx Trachea Lung Number of Surgical Interventions Needed Surgical Intervals Prior Therapy
1 Best et al. [5] United States 2017 20 F Juvenile Y Y Y -- 3 weeks Local: Cidofovir, bevacizumab, photodynamic therapy.
Systemic. Interferon alpha
2 Best et al. [5] United States 2017 12 F Juvenile Y Y Y -- 1–4 weeks Local: Cidofovir Systemic: Interferon alpha, propanolol, celecoxib, Gardasil
3 Best et al. [5] United States 2017 16 F Juvenile Y N N -- 4–6 weeks Local: Cidofovir Systemic: Celecoxib
4 Best et al. [5] United States 2017 10 M Juvenile Y Y Y -- 4 weeks Local: Cidofovir Systemic: Interferon alpha, indole 3 carbinol, celecoxib
5 Best et al. [5] United States 2017 18 M Juvenile Y Y Y -- 6 weeks Local: Cidofovir, Bevacizumab Systemic: Interferon, leflunomide
6 Best et al. [5] United States 2017 21 M Juvenile Y Y Y -- 6 weeks Local: Cidofovir
7 Best et al. [5] United States 2017 86 M Adult N N Y -- 3 months Local: Cidofovir
8 Best et al. [5] United States 2017 62 M Adult N Y Y -- 12 months None
9 Cuestas et al. [6] Argentina 2019 6 M Juvenile N Y Y 2 4 weeks None
10 Nagel et al. [7] Germany 2009 32 M Juvenile N Y N 4 per year during 12 years 8 weeks Local: Interferon, Cidofovir
11 Gates et al. [8] United States 2020 0.583333 M Juvenile Y Y N -- 10 months None
12 Zur et al. [9] United States 2016 12 F Juvenile Y Y Y >500 1–4 weeks Local: Cidofovir, interferon alpha Systemic: Celecoxib, Propanolol, Azythormycin, Gardasil
13 Mhor et al. [10] Germany 2014 43 M Juvenile N Y Y >30 -- Multiple laser ablations
14 Mhor et al. [10] Germany 2014 49 M Adult Y N N 2 6 months 2 laser ablation
15 Mhor et al. [10] Germany 2014 56 F Adult Y N N 16 -- 16 Laser ablations
16 Mhor et al. [10] Germany 2014 8 F Juvenile Y Y Y >30 -- Multiple laser ablations Local: interferon-alpha, cidofovir and celecoxib
17 Mhor et al. [10] Germany 2014 34 M Adult Y N N 6 -- laser vaporization and radical surgery via midfacial degloving, radiotherapy,
18 Fernandez-Bussy et al. [11] Chile 2017 42 M Adult N Y N 3 -- Local: ablation with argon plasma coagulation
19 Carnevale et al. [12] Spain 2018 5 M Juvenile Y Y Y 10 -- Multiples surgeries and laser ablations Local: Intepheron alpha, Cidofovir Systemic: Gardasil
20 Carnevale et al. [12] Spain 2018 9 F Juvenile Y Y N 47 -- Mulple surgeries
21 Hamdi et al. [13] United States 2020 12 M Juvenile Y Y Y 54 -- Multiples surgeries and laser ablations Local: Intepheron alpha, Cidofovir Systemic: Indole 3 Carbinol
22 Hamdi et al. [13] United States 2020 6 M Juvenile Y N N 34 - Local: Cidofovir
23 Bedoya et al. [14] United States 2017 87 M Adult N N Y 5 -- Local: Cidofovir, intralesional stent
Systemic: Gardasil
24 Bedoya et al. [14] United States 2017 63 M Adult Y Y Y >6 -- --
25 Evers et al. [15] United States 2020 Betweenn 8 and 56 Both Juvenile and adult Y Y Y >10 -- Lobe resection, surgical interventions, laser ablations, radiochemotherapy
27 Ortiz et al. [16] Colombia 2021 Betweenn 1 and 8 Both Juvenile Y Y Y >10 -- Debridement procedures
28 Gorelik et al. [17] United States 2021 5 F Juvenile Y N N 1 -- Debridement procedures
29 Goyal et al. [18] India 2021 4 and 24 F Juvenile Y N N >10 -- Local Bevacizumab
Twenty-six of the 34 patients had laryngeal lesions, 19 had tracheal lesions, and 17 had lung lesions. Twelve patients had tracheal, laryngeal, and lung lesions. Before bevacizumab therapy, 24 of the 34 patients had undergone surgical procedures. The reported interventions had a median of 13 interventions (min = 3 interventions and max = 500 interventions).
Table 2 summarizes SB treatment, dosage, and outcomes in patients with RRP. Various doses were reported at various schemes. The most commonly reported SB dose was 10 mg/kg, which was received by 25 (73.5%) patients. The initial dose intervals with this dose ranged from 2 to 5 weeks. Two patients received 5 mg/kg with a 2-week interval between doses, and one received the same dose but with a 3-week interval. Two patients were given 15 mg/kg at 3-week intervals. The authors reported an initial dose of 5 mg/kg in four patients, followed by one increase to 7.5 mg/kg and two increases to 10 mg/kg.
Table 2. Systemic bevacizumab treatment, dosage and outcomes in patients with RRP. CR, Complete Regression, PR, Partial Regression, VGPR, very good partial remission, NA Not Applicable.
Case Author Country Year Prior Therapy Dose (mg/kg) Inicial Dosing Interval (q Week) Duration of Treatment (Months) Stable Dosing Interval (q Week) Total Cycles Received Response Pulmonary Response Surgical Interval Post Bevacizumab Side Events
1 Best et al. [5] United States 2017 Local: Cidofovir, bevacizumab, photodynamic therapy.
Systemic. Interferon alpha		 10 3 12 8 -- PR Not known q3 months Treatment changed secondary to diagnosis of malignancy
2 Best et al. [5] United States 2017 Local: Cidofovir
Systemic: Interferon alpha, propanolol, celecoxib, Gardasil		 10 4 21 8 -- PR CR q4 months Proteinuria
3 Best et al. [5] United States 2017 Local: Cidofovir
Systemic: Celecoxib		 10 2 10 12 -- CR . No surgery required None
4 Best et al. [5] United States 2017 Local: Cidofovir
Systemic: Interferon alpha, indole 3 carbinol, celecoxib		 5 3 18 3 -- PR Stable q6 months None
5 Best et al. [5] United States 2017 Local: Cidofovir, Bevacizumab
Systemic: Interferon, leflunomide		 10 3 7 6 -- PR Not known q6 week with no excision needed Hemoptysis
6 Best et al. [5] United States 2017 Local: Cidofovir 10 3 5 12 -- PR Not known q3 months None
7 Best et al. [5] United States 2017 Local: Cidofovir 10 3 10 8 -- PR PR No surgery required None
8 Best et al. [5] United States 2017 None 10 2 8 6 -- PR PR No surgery required None
9 Cuestas et al. [6] Argentina 2019 None 10 4 6 12 -- PR PR No surgery required None
10 Nagel et al. [7] Germany 2009 Local: Interferon, Cidofovir 10 3 6 10 -- CR CR No surgery required None
11 Gates et al. [8] United States 2020 None 5 and then 10 4 12 . -- PR - No surgery required None
12 Zur et al. [9] United States 2016 Local: Cidofovir, interferon alpha
Systemic: Celecoxib, Propanolol, Azythormycin, Gardasil		 10 4–5 15.5 14 - CR CR Tracheal debridement at 12 months after bevacizumab starting.
Laryngeal debribement at 15 months after bevacizumab starting.		 Mild proteinuria
13 Mhor et al. [10] Germany 2014 Multiple laser ablations 10 2 27 16 16 VGPR PR No surgery required Hypertension
14 Mhor et al. [10] Germany 2014 2 laser ablation 10 3 2 . 3 PR NA Laryngectomy for malignant transformation None
15 Mhor et al. [10] Germany 2014 16 Laser ablations 10 -- . . 6 VGPR NA One infraglottic lesion, which had not responded to the same extent was treated with additional laser therapy a los 14 días None
16 Mhor et al. [10] Germany 2014 Multiple laser ablations
Local: interferon-alpha, cidofovir and celecoxib		 5 2 2 12 9 VGPR CR One surgery due to granulloma at the distal end of the tracheal cannula None
17 Mhor et al. [10] Germany 2014 laser vaporization and radical surgery via midfacial degloving, radiotherapy, 15 3 2 . 6 CR NA No surgery required None
18 Fernandez-Bussy et al. [11] Chile 2017 Local: ablation with argon plasma coagulation 5 and then 10 3 4 12 6 CR NA No surgery required None
19 Carnevale et al. [12] Spain 2018 Multiples surgeries and laser ablations
Local: Intepheron alpha, Cidofovir
Systemic: Gardasil		 10 4 46 10 -- CR CR Two surgical procedures due to laryngeal lesions Mild proteinuria
20 Carnevale et al. [12] Spain 2018 Mulple surgeries 5 and then 7.5 3 6 3 8 CR NA No surgery required None
21 Hamdi et al. [13] United States 2020 Multiples surgeries and laser ablations
Local: Intepheron alpha, Cidofovir
Systemic: Indole 3 Carbinol		 10 3 54 3 15 CR PR Seven microdebriders None
22 Hamdi et al. [13] United States 2020 Local: Cidofovir 10 1 . . 1 CR CR One surgery needed None
23 Bedoya et al. [14] United States 2017 Local: Cidofovir, intralesional stent
Systemic: Gardasil		 5 2 -- 6 - VGPR VGPR No surgery required Hemoptysis
24 Bedoya et al. [14] United States 2017 -- 10 2 -- 3 -- VGPR VGPR No surgery required Mild Increase of basal hypertension
25 Evers et al. [15] United States 2020 middle lobe resection with lymphadenectomy 10 2 -- 3 68 VGPR VGPR 51 months Proteinuria, Hypertension
26 Evers et al. [15] United States 2020 -- 10 3 -- 3 3 PR NA laser ablation None
27 Evers et al. [15] United States 2020 Laser ablations 10 10 -- -- 34 CR NA 17 months Proteinuria, Hypertension
28 Evers et al. [15] United States 2020 Laser ablations 5 2 -- -- 33 CR VGPR 32 months None
29 Evers et al. [15] United States 2020 -- 15 3 -- -- 15 PR NA -- None
30 Ortiz et al. [16] Colombia 2021 Tracheostomy and surgical debridement 10 3 -- -- 3 VGPR NA -- None
31 Ortiz et al. [16] Colombia 2021 Tracheostomy 10 3 -- -- 3 CR NA -- None
32 Ortiz et al. [16] Colombia 2021 Debridement 10 3 -- -- 4 CR NA -- None
33 Gorelik et al. [17] United States 2021 Surgical debridement, Intralesional Bevacizumab 10 3 -- -- 8 CR NA -- None
34 Goyal et al. [18] India 2021 three doses of HPV vaccine Cervarix 10 3 -- -- -- VGPR NA -- None

References

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  2. Derkay, C.S.; Faust, R.A. Recurrent Respiratory Papillomatosis, 6th ed.; Cummings Otolaryngology; Elsevier Inc.: Amsterdam, The Netherlands, 2018; pp. 3142–3157.e3.
  3. Fortes, H.R.; von Ranke, F.M.; Escuissato, D.L.; Neto, C.A.A.; Zanetti, G.; Hochhegger, B.; Souza, C.A.; Marchiori, E. Recurrent respiratory papillomatosis: A state-of-the-art review. Respir. Med. 2017, 126, 116–121.
  4. Kashima, H.; Leventhal, B.; Mounts, P.; Hruban, R.H. Sites of Predilection in Recurrent Respiratory Papillomatosis. Ann. Otol. Rhinol. Laryngol. 1993, 102, 580–583.
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  6. Cuestas, G.; Rodríguez, V.; Doormann, F.; Munzón, P.B.; Munzón, G.B. Tracheobronchial and Pulmonary Papillomatosis without Involvement of the Larynx Treated with Intravenous Bevacizumab in a Child. Archivos Argentinos de Pediatria. 2019, 117, E72–E76.
  7. Nagel, S.; Busch, C.; Blankenburg, T.; Schütte, W. Behandlung der Respiratorischen Papillomatose Kasuistik zur Systemischen Therapie mit Bevacizumab1. Pneumologie 2009, 63, 387–389.
  8. Gates, C.; Tomboc, P.; Allison, A.; Carr, M. Bevacizumab as adjuvant therapy for recurrent respiratory papillomatosis in an infant. Int. J. Pediatr. Otorhinolaryngol. 2020, 129, 109762.
  9. Zur, K.B.; Fox, E. Bevacizumab Chemotherapy for Management of Pulmonary and Laryngotracheal Papillomatosis in a Child. Laryngoscope 2017, 127, 1538–1542.
  10. Mohr, M.; Schliemann, C.; Biermann, C.; Schmidt, L.-H.; Kessler, T.; Schmidt, J.; Wiebe, K.; Müller, K.-M.; Hoffmann, T.K.; Groll, A.H.; et al. Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis. Oncol. Lett. 2014, 8, 1912–1918.
  11. Fernandez-Bussy, S.; Labarca, G.; Vial, M.R.; Soto, R.; Mehta, H.J.; Jantz, M.; Majid, A.; Burotto, M. Recurrent Respiratory Papillomatosis and Bevacizumab Treatment. Am. J. Respir. Crit. Care Med. 2018, 197, 539–541.
  12. Carnevale, C.; La Cierva, L.F.; Til-Pérez, G.; Peña-Zarza, J.A.; Osona-Rodriguez, B.; Martinez-Lozano, J.; Sarría-Echegaray, P.; Arancibia-Tagle, D.; Tomás-Barberán, M. Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children. Laryngoscope 2019, 129, 1001–1004.
  13. Hamdi, O.; Dome, J.; Zalzal, G.; Preciado, D. Systemic Bevacizumab for End-stage Juvenile Recurrent Respiratory Papillomas: A Case Report. Int. J. Pediatric Otorhinolaryngol. 2020, 128, 109706.
  14. Bedoya, A.; Glisinski, K.; Clarke, J.; Lind, R.N.; Buckley, C.E.; Shofer, S. Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center Experience of Two Cases. Am. J. Case Rep. 2017, 18, 842–846.
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  17. Gorelik, D.; Frantz, A.; Dome, J.S.; Reilly, B.K. Recurrent Respiratory Papillomatosis With Complete Response to Systemic Bevacizumab Therapy. Ear Nose Throat J. 2021, 4–5.
  18. Goyal, A.; Kapoor, D.; Saha, R. Systemic and Intralesional Bevacizumab in Juvenile Onset Recurrent Respiratory Papillomatosis: A Report of Two Cases. Indian J. Otolaryngol. Head Neck Surg. 2021, 1–4.
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Subjects: Allergy
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Laura Torres-Canchala ,
Daniela Cleves-Luna
, Oriana Arias-Valderrama ,
Estephania Candelo
, María Angelica Guerra ,
Harry Pachajoa
,
Manuela Olaya
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Update Date: 09 Feb 2023
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