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Office-based intralesional cidofovir injections for nasal septal papilloma: A pilot study
Otolaryngology–Head and Neck Surgery (2006) 135, 149-151
SHORT SCIENTIFIC COMMUNICATION
Office-based intralesional cidofovir injections for nasal septal papilloma: A pilot study Larry J. Shemen, MD, and Yelizaveta Shnayder, MD, New York, New York OBJECTIVES: To determine if nasal septal papilloma is responsive to intralesional cidofovir injections. METHODS: Five adult males, ages 37 to 57, presented with nasal septal or columellar papilloma. Three lesions had been previously excised with the laser and recurred. The lesions were injected with cidofovir on a monthly basis until complete resolution or any residual lesion was excised afterwards with the laser. RESULTS: All patients achieved disease remission sustained over 10 to 24 months. Overall doses were much lower than those described for laryngeal papillomatosis and no toxic effects were observed. CONCLUSIONS: Office-based intralesional injections of cidofovir may show benefit in the treatment of nasal septal papilloma. EBM rating: C-4 © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
R
ecent investigations have suggested that human papillomaviruses (HPV) may be involved in the development of nasal septal papillomas.1,2 HPV 6b and 11 have been detected by in situ hybridization and PCR techniques in exophytic sinonasal papillomas.3,4 Cidofovir is a cytosine nucleotide analog that has been shown to have antiviral activity against herpes viruses, adenoviruses, and HPV. Its mechanism of action is through the active intracellular metabolite cidofovir dehydrate, which inhibits viral DNA polymerase. Cidofovir is currently approved by the Food and Drug Administration to treat cytomegalovirus retinitis in AIDS patients. There is a growing body of literature describing safe and successful use of intralesional injections of cidofovir in severe recurrent laryngeal papillomatosis in children and adults. From the Department of Otolaryngology, New York University School of Medicine; Lenox Hill Hospital; and Manhattan Eye Ear Nose and Throat Hospital. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, New York, NY, September 19-22, 2004.
We describe the use of intralesional injections of cidofovir in 5 adult patients with nasoseptal papilloma with a follow-up of 10 months to 2 years.
MATERIALS AND METHODS Five consecutive patients with biopsy-proven nasal septal papillomas were entered into the study. The patients were fully explained the proposed treatment protocol and informed consent was obtained. The cidofovir was mixed in a 5-cc syringe with saline and was injected into the base of the papilloma. The patients were followed monthly afterwards until complete resolution. A 52-year-old Caucasian male presented with a severalyear history of left nasal obstruction. Physical exam was remarkable for a well-circumscribed exophytic mass arising from left nasal sill, extending onto the left caudal septum, measuring 1.5 cm in greatest dimension. The patient underwent repeated laser resections of the lesion. When the papilloma recurred after 3 excisions, it was injected with cidofovir solution to a total cumulative dose of 68.75 mg. There was complete regression of the lesion with no recurrence after 24 months. A 53-year-old Caucasian male presented with a 10-year history of right nasal obstruction and intermittent epistaxis. He admitted to smoking cigars. Physical exam disclosed a 1-cm polypoid lesion located over the right anterior septum and membranous columella. The lesion was initially excised with the laser, but recurred. It was injected with cidofovir solution to a total dose of 37.5 mg and completely regressed within 4 weeks. The Reprint requests: Larry J. Shemen, MD, 233 East 69 Street, Suite #1D, New York, NY 10021. E-mail address: [email protected].
0194-5998/$32.00 © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2005.12.028
150
Otolaryngology–Head and Neck Surgery, Vol 135, No 1, July 2006
patient had recurrence after 12 months (he continues to smoke) and this was successfully treated with repeat injection. He is now disease free for 12 months. A 57-year-old Caucasian male presented with a 20-year history of right nasal obstruction and intermittent epistaxis. Physical exam showed a right nasal 1.5-cm papilloma. It was injected with cidofovir solution to 37.5 mg total. The lesion completely regressed and remains so 18 months later (Figs 1 and 2). A 37-year-old Asian male presented with a 2-month history of a left anterior nasal mass. Examination disclosed a 0.5-cm exophytic papilloma on the caudal edge of the septum and membranous columella. The lesion was injected with cidofovir solution to a total of 37.5 mg and the residual excised 1 month later using the laser. He remains disease free at 12 months. A 47-year-old Caucasian male presented with a 6-month history of left nasal obstruction. This was previously excised by another otolaryngologist and subsequently recurred. He admitted to topical nasal substance abuse. Physical examination was pertinent for multiple papillomas involving the septum and the inferior turbinate, the average measuring 1 cm. The lesions were injected with cidofovir solution to a total of 37.5 mg and then the residual lesion excised using the laser. He remains disease free at 10 months.
DISCUSSION Conventional techniques of papilloma excision are hampered in that only the visible lesion can be removed, and the disease can therefore recur. On the other hand, antiviral therapy lessens the viral burden and eradicates the lesion locally.5 Cidofovir was first reported for the treatment of severe laryngeal papillomatosis by Snoeck in 1998.6 It is one of the most potent inhibitors of papilloma virus growth. Moreover, the drug specifically targets cells containing papilloma virus.
Figure 2
After 2 cidofovir injections (Case #3).
It has, however, been extensively employed for the treatment of laryngeal papillomatosis.7 Initially, the decision was made to try cidofovir for recurrent nasal papillomatosis. The objective then changed to treating nasal papillomas on initial presentation. The dose protocol was based on studies with laryngeal papillomatosis in both children and adults. Any residual lesion could then be resected with the CO2 laser. The additional cost of the drug (as compared to excision alone) is countered by the decreased recurrence rate and extended disease-free interval. The patients must be advised to stop smoking or substance abuse. The overall cumulative doses of intralesional cidofovir used in the above 5 cases (38-69 mg) were below the doses described for recurrent laryngeal papillomatosis in adults (up to 685 mg) and substantially lower than those used in cytomegalovirus retinitis (systemic therapy with 5 mg/kg/ week). Although there have been concerns with potential tumerigenicity of cidofovir in animal studies, no human subjects to date have developed laryngeal carcinoma after intralesional injections of cidofovir. Our experience with 5 patients suggests that office-based treatment with intranasal cidofovir injections may show benefit in treating initial and recurrent nasal septal papilloma. Although our follow-up was short (24 months), only 1 of the 5 patients had recurrence, and he admitted to continued smoking. No adverse effects related to the therapy were noted. The success enjoyed with this treatment has prompted us to consider a similar protocol for the treatment of oral and oropharyngeal papillomas. Larger studies with longer follow-up will be necessary to validate long-term treatment response.
REFERENCES
Figure 1
After a single cidofovir injection (Case #3).
1. Kraft M, Simmen D, Casa R, et al. Significance of human papillomavirus in sinonasal papillomas. J Laryngol Otol 2001;115(9):709 –14. 2. Buchwald C, Franzmann MB, Tos M. Sinonasal papillomas: a report of 82 cases in Copenhagen County. Laryngoscope 1995;105(1):72–9.
Shemen and Shnayder
Office-based intralesional cidofovir injections for . . .
3. Sarkar FH, Visscher DW, Kintanar EB, et al. Sinonasal Schneiderian papillomas: human papillomavirus typing by polymerase chain reaction. Mod Pathol 1992;5(3):329 –32. 4. Hyams VJ. Papillomas of the nasal cavity and paranasal sinuses. A clinicopathological study of 315 cases. Ann Otol Rhinol Laryngol 1971;80(2):192–206.
151
5. Trizna Z. Viral diseases of the skin. Paediatr Drugs 2002;4:9 –19. 6. Snoeck R, Wellens W, Desloovere C, et al. Treatment of severe laryngeal papillomatosis with intralesional injections of cidofivir. J Med Virol 1998;54:219 –25. 7. Kimberlin D. Pharmacotherapy of recurrent respiratory papillomatosis. Expert Opin Pharmacother 2002;3:1091–9.
SHORT SCIENTIFIC COMMUNICATION
Office-based intralesional cidofovir injections for nasal septal papilloma: A pilot study Larry J. Shemen, MD, and Yelizaveta Shnayder, MD, New York, New York OBJECTIVES: To determine if nasal septal papilloma is responsive to intralesional cidofovir injections. METHODS: Five adult males, ages 37 to 57, presented with nasal septal or columellar papilloma. Three lesions had been previously excised with the laser and recurred. The lesions were injected with cidofovir on a monthly basis until complete resolution or any residual lesion was excised afterwards with the laser. RESULTS: All patients achieved disease remission sustained over 10 to 24 months. Overall doses were much lower than those described for laryngeal papillomatosis and no toxic effects were observed. CONCLUSIONS: Office-based intralesional injections of cidofovir may show benefit in the treatment of nasal septal papilloma. EBM rating: C-4 © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
R
ecent investigations have suggested that human papillomaviruses (HPV) may be involved in the development of nasal septal papillomas.1,2 HPV 6b and 11 have been detected by in situ hybridization and PCR techniques in exophytic sinonasal papillomas.3,4 Cidofovir is a cytosine nucleotide analog that has been shown to have antiviral activity against herpes viruses, adenoviruses, and HPV. Its mechanism of action is through the active intracellular metabolite cidofovir dehydrate, which inhibits viral DNA polymerase. Cidofovir is currently approved by the Food and Drug Administration to treat cytomegalovirus retinitis in AIDS patients. There is a growing body of literature describing safe and successful use of intralesional injections of cidofovir in severe recurrent laryngeal papillomatosis in children and adults. From the Department of Otolaryngology, New York University School of Medicine; Lenox Hill Hospital; and Manhattan Eye Ear Nose and Throat Hospital. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, New York, NY, September 19-22, 2004.
We describe the use of intralesional injections of cidofovir in 5 adult patients with nasoseptal papilloma with a follow-up of 10 months to 2 years.
MATERIALS AND METHODS Five consecutive patients with biopsy-proven nasal septal papillomas were entered into the study. The patients were fully explained the proposed treatment protocol and informed consent was obtained. The cidofovir was mixed in a 5-cc syringe with saline and was injected into the base of the papilloma. The patients were followed monthly afterwards until complete resolution. A 52-year-old Caucasian male presented with a severalyear history of left nasal obstruction. Physical exam was remarkable for a well-circumscribed exophytic mass arising from left nasal sill, extending onto the left caudal septum, measuring 1.5 cm in greatest dimension. The patient underwent repeated laser resections of the lesion. When the papilloma recurred after 3 excisions, it was injected with cidofovir solution to a total cumulative dose of 68.75 mg. There was complete regression of the lesion with no recurrence after 24 months. A 53-year-old Caucasian male presented with a 10-year history of right nasal obstruction and intermittent epistaxis. He admitted to smoking cigars. Physical exam disclosed a 1-cm polypoid lesion located over the right anterior septum and membranous columella. The lesion was initially excised with the laser, but recurred. It was injected with cidofovir solution to a total dose of 37.5 mg and completely regressed within 4 weeks. The Reprint requests: Larry J. Shemen, MD, 233 East 69 Street, Suite #1D, New York, NY 10021. E-mail address: [email protected].
0194-5998/$32.00 © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2005.12.028
150
Otolaryngology–Head and Neck Surgery, Vol 135, No 1, July 2006
patient had recurrence after 12 months (he continues to smoke) and this was successfully treated with repeat injection. He is now disease free for 12 months. A 57-year-old Caucasian male presented with a 20-year history of right nasal obstruction and intermittent epistaxis. Physical exam showed a right nasal 1.5-cm papilloma. It was injected with cidofovir solution to 37.5 mg total. The lesion completely regressed and remains so 18 months later (Figs 1 and 2). A 37-year-old Asian male presented with a 2-month history of a left anterior nasal mass. Examination disclosed a 0.5-cm exophytic papilloma on the caudal edge of the septum and membranous columella. The lesion was injected with cidofovir solution to a total of 37.5 mg and the residual excised 1 month later using the laser. He remains disease free at 12 months. A 47-year-old Caucasian male presented with a 6-month history of left nasal obstruction. This was previously excised by another otolaryngologist and subsequently recurred. He admitted to topical nasal substance abuse. Physical examination was pertinent for multiple papillomas involving the septum and the inferior turbinate, the average measuring 1 cm. The lesions were injected with cidofovir solution to a total of 37.5 mg and then the residual lesion excised using the laser. He remains disease free at 10 months.
DISCUSSION Conventional techniques of papilloma excision are hampered in that only the visible lesion can be removed, and the disease can therefore recur. On the other hand, antiviral therapy lessens the viral burden and eradicates the lesion locally.5 Cidofovir was first reported for the treatment of severe laryngeal papillomatosis by Snoeck in 1998.6 It is one of the most potent inhibitors of papilloma virus growth. Moreover, the drug specifically targets cells containing papilloma virus.
Figure 2
After 2 cidofovir injections (Case #3).
It has, however, been extensively employed for the treatment of laryngeal papillomatosis.7 Initially, the decision was made to try cidofovir for recurrent nasal papillomatosis. The objective then changed to treating nasal papillomas on initial presentation. The dose protocol was based on studies with laryngeal papillomatosis in both children and adults. Any residual lesion could then be resected with the CO2 laser. The additional cost of the drug (as compared to excision alone) is countered by the decreased recurrence rate and extended disease-free interval. The patients must be advised to stop smoking or substance abuse. The overall cumulative doses of intralesional cidofovir used in the above 5 cases (38-69 mg) were below the doses described for recurrent laryngeal papillomatosis in adults (up to 685 mg) and substantially lower than those used in cytomegalovirus retinitis (systemic therapy with 5 mg/kg/ week). Although there have been concerns with potential tumerigenicity of cidofovir in animal studies, no human subjects to date have developed laryngeal carcinoma after intralesional injections of cidofovir. Our experience with 5 patients suggests that office-based treatment with intranasal cidofovir injections may show benefit in treating initial and recurrent nasal septal papilloma. Although our follow-up was short (24 months), only 1 of the 5 patients had recurrence, and he admitted to continued smoking. No adverse effects related to the therapy were noted. The success enjoyed with this treatment has prompted us to consider a similar protocol for the treatment of oral and oropharyngeal papillomas. Larger studies with longer follow-up will be necessary to validate long-term treatment response.
REFERENCES
Figure 1
After a single cidofovir injection (Case #3).
1. Kraft M, Simmen D, Casa R, et al. Significance of human papillomavirus in sinonasal papillomas. J Laryngol Otol 2001;115(9):709 –14. 2. Buchwald C, Franzmann MB, Tos M. Sinonasal papillomas: a report of 82 cases in Copenhagen County. Laryngoscope 1995;105(1):72–9.
Shemen and Shnayder
Office-based intralesional cidofovir injections for . . .
3. Sarkar FH, Visscher DW, Kintanar EB, et al. Sinonasal Schneiderian papillomas: human papillomavirus typing by polymerase chain reaction. Mod Pathol 1992;5(3):329 –32. 4. Hyams VJ. Papillomas of the nasal cavity and paranasal sinuses. A clinicopathological study of 315 cases. Ann Otol Rhinol Laryngol 1971;80(2):192–206.
151
5. Trizna Z. Viral diseases of the skin. Paediatr Drugs 2002;4:9 –19. 6. Snoeck R, Wellens W, Desloovere C, et al. Treatment of severe laryngeal papillomatosis with intralesional injections of cidofivir. J Med Virol 1998;54:219 –25. 7. Kimberlin D. Pharmacotherapy of recurrent respiratory papillomatosis. Expert Opin Pharmacother 2002;3:1091–9.