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Copyright ©ERS Journals Ltd 2001
Successful treatment of severe respiratory papillomatosis with intravenous cidofovir and interferon 
-2b
1 Second and 2 First Medical Dept/Pumologisches Zentrum, 3 Institute for Pathology and Microbiology/Baumgartner Höhe and 4 First Surgical Dept/Krankenanstalt Rudolfstiftung,
CORRESPONDENCE: C. Armbruster, Mantlegasse 23/2/12, A-1130, Vienna, Austria. Fax: 43 18775820
Keywords: bronchoscopy, cidofovir, interferon 
-2b, respiratory system, squamous papillomatosis
Received: February 21, 2000
Accepted August 7, 2000
Abstract
In contrast to uncomplicated juvenile laryngeal papillomas which may regress spontaneously, papillomatosis involving pulmonary parenchyma is associated with a poor outcome.
This report represents the case of a 34 yr-old female in whom respiratory papillomatosis resulted in voice problems and recurrent pneumonias due to bronchial obstruction. A computed tomographic scan of the chest showed worsening bilateral round cavitating consolidations. Bronchoscopy revealed polypoid lesions of the right vocal cord and the midtrachea which were confirmed as squamous papillomatosis by histology.
Interferon (IFN)
These data provide support that severe respiratory papillomatosis can be safely treated by interferon
-2b treatment was inefficient as was cidofovir monotherapy on a maintenance basis. Six months of IFN--2b and cidofovir in combination led to a complete macroscopic disappearance of the laryngeal lesions and to an impressive regression of the tracheal papillomas and of the intrapulmonary consolidations. -2b and cidofovir in combination. Probably the same mechanisms as in ribavirin plus interferon -2b, in the treatment of patients with chronic hepatitis C, are responsible for the therapeutic success in this case.
Case report
A 34 yr-old woman was admitted to our hospital with respiratory papillomatosis in 1997. She had undergone more than two hundred microlaryngoscopies since she had been 7 yrs old and suffered from voice problems and recurrent pneumonias due to bronchial obstruction. Interferon -2b treatment (5x106 units, three times a week) had been instituted at the age of 30, but frequent recurrences remained to be a problem.
A computed tomographic scan of the chest showed bilateral round cavitating consolidations which worsened during the subsequent 18 months after admission (fig. 1
). Bronchoscopy under generalized anesthesia was first performed in April 1997 and revealed polypoid lesions of the right vocal cord and the midtrachea. The histology of the tracheal and laryngeal biopsy specimens confirmed the diagnosis of squamous papillomatosis. HPV type 6 and 11 were demonstrated using polymerase chain reaction (Hybrid Capture II Test, Digene Corp., Beltsville, MD, USA).
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–2b combination therapy (December 1999).Between 1997 and October 1998 the patient was treated with Argon laser vaporization twice. IFN-
-2b treatment was continued until October 1998, when the patient was admitted again with large polypoid squamous papillomas of both vocal cords and a circumferential polypoid tumour involving the trachea (fig. 2). Based on these endoscopical findings IFN--2b therapy was stopped due to lack of efficacy and cidofovir treatment was instituted (induction treatment: 5 mg·kg–1 bodyweight once a week during two weeks, maintenance treatment: 5 mg·kg–1 bodyweight every 2 weeks). Endoscopic control in December 1998 showed a regression of the laryngeal papillomas but there was evidence of progressing papillomatous lesions in the trachea (fig. 2).
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Due to recurrence of papillomatosis in the larynx, IFN-
-2b was added to cidofovir. Six months of this combination therapy led to a complete macroscopic disappearance of the laryngeal lesions and to a marked response of the papillomas in the trachea (fig. 2
). A computed tomographic scan of the chest in December 1999 showed no evidence of endobronchial lesions and an impressive regression of the intrapulmonary consolidations (fig. 1). At the given dose (5 mg·kg–1 bodyweight every two weeks) cidofovir was well tolerated and no haematotoxicity, nephrotoxicity or hepatotoxicity could be detected during the 12-month treatment period.
Discussion
The course of respiratory papillomatosis is variable. In contrast to uncomplicated juvenile laryngeal papillomas which may regress spontaneously, papillomatosis involving pulmonary parenchyma is associated with a poor outcome 4. The effect of intratumoural injections of cidofovir opens perspectives for HPV-induced lesions, which are easily accessible for injection therapy, but endobronchial and intrapulmonary lesions represent a therapeutic dilemma 1–3.
Pransky et al. 2 recently described a dramatic response of papillomatous lesions to intralesional cidofovir and IFN-–2a in a child. To the best of the authors' knowledge, the efficacy of this treatment regimen in adult respiratory papillomatosis involving pulmonary parenchyma has not been reported at the time of our study.
The data presented herein provide support that combination therapy with cidofovir on a maintenance basis and interferon -2b is efficient in adult respiratory papillomatosis. It is possible that the same mechanisms involved in ribavirin plus interferon--2b in the treatment of patients with chronic hepatitis C are responsible for the therapeutic success in our case 5.
References
- Snoeck R, Wellens W, Desloovere C, et al. Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir ((S)–1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine). J Med Virol 1998;54:219–225.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
- Pransky SM, Margit AE, Kearns DB, Kang DR, Duncan NO. Intralesional cidofovir for recurrent respiratory papillomatosis in children. Arch Otolaryngol Head Neck Surg 1999;125:1143–1148.
[Abstract/Free Full Text] - Van Cutsem E, Snoeck R, Van Ranst M, et al. Successful treatment of a squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine. J Med Virol 1995;45:230–235.[Web of Science][Medline] [Order article via Infotrieve]
- Williams SD, Jamieson DH, Prescott CA. Clinical and radiological features in three cases of pulmonary involvement from recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 1994;30:71–77.[Medline] [Order article via Infotrieve]
- Barbaro G, Di Lorenzo G, Belloni G, et al. Interferon alpha–2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial. Am J Med 1999;107:112–118.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
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