eMedicine Specialties > Pulmonology > Lung Tumors

Recurrent Respiratory Papillomatosis: Treatment & Medication

Author: Eloise M Harman, MD, Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Mar 6, 2008

Treatment

Medical Care

The goals of therapy are to relieve airway obstruction, improve voice quality, and facilitate remission. The primary treatment involves repeated surgical debulking, usually by means of microdebridement, angiolytic laser, cryotherapy, or carbon dioxide laser. This may be followed by an injection of cidofovir into the resection site in patients with moderate-to-severe disease. Compared with microdebridement and laser procedures, surgical resection may be associated with a higher risk of complications (eg, tracheal stenosis). Tracheostomy may be needed if significant airway obstruction occurs.

Because the disease is rare, large-scale trials of medical therapies have not been possible; however, several agents are available that appear to increase the intervals between need for resection. These include intralesional cidofovir,5,6,7,8 oral indole-3-carbinol,9,10 interferon,11,12 and photodynamic therapy.13 Agents that demonstrate variable effect include acyclovir14 and retinoic acid.15 Agents that have shown some benefit in case series and are undergoing further study include cimetidine, zinc, intralesional mumps vaccine, and cyclooxygenase-2 inhibitors. With the increased use of intralesional cidofovir, interferon therapy is now infrequently used.

A vaccine for prevention of genital HPV infection in young women was approved in 2006. This vaccine protects against HPV types 6, 11, 16, and 18 and therefore has promise for decreasing the incidence of RRP.16 Vaccine therapy for those already affected with HPV is under study.

Surgical Care

Multiple resections are typical. Microdebridement of laryngeal lesions is often preferred to laser therapy. With anesthesia induction, take extreme care to maintain the already-compromised airway. The surgical team should be prepared for the possibility that emergency tracheostomy may be required. A survey of anesthesiologists regarding anesthesia techniques for patients undergoing laser procedures for RRP indicated the following preferences:

  • Laser-safe endotracheal tube (46%)
  • Jet ventilation (26%)
  • Apneic technique (16%)
  • Spontaneous ventilation (12%)
  • Preferred anesthetic agents - Halothane and propofol

Physicians may combine surgery with an injection of the surgical bed with medication that may slow regrowth. Cidofovir is effective in a significant proportion of patients and has replaced intralesional interferon.

The carbon dioxide laser previously was the preferred method for resection of papillomas because it affords good hemostasis and minimizes potential thermal injury of surrounding healthy tissues. The use of microdebridement using angled oscillating blades that incorporate suction and irrigation or the use of pulsed dye laser is now the preferred resection method at many centers. These offer the advantage of shorter operative times, potential for outpatient surgery, decreased risk to personnel, and avoidance of the risk of airway burns. These methods may also decrease recurrence rates. Repeat evaluation of the airway in newly diagnosed RRP may be required as frequently as every 2-4 weeks.

Photodynamic therapy, in small trials, has been shown to slow the rate of papilloma growth. Hematoporphyrins are taken up selectively by neoplastic cells and are used as photosensitizing agents for subsequent laser therapy. Dihematoporphyrin ether (DHE) usually is administered 2-3 days before surgery. Delivery of argon laser light to the affected area via laryngoscope or bronchoscope activates the drug.

The virus may be aerosolized during surgical procedures; therefore, staff should take particular care to wear goggles and a particulate barrier facemask or shield during procedures.

Consultations

Consider participation in ongoing clinical trials of various therapies.

Diet

Animal studies and observational studies in patients with RRP indicate that a diet high in cruciferous vegetables (eg, cabbage, cauliflower, broccoli, Brussels sprouts) may have a favorable effect.9 Researchers hypothesize that indole-3-carbinol is the active agent in these vegetables. Treatment with indole-3-carbinol is beneficial for persons with RRP.

Medication

No drug can cure RRP. Several drugs appear to slow the growth of papillomas and increase the interval between necessary surgical debulking procedures. Intralesional cidofovir is frequently effective; however, because optimal dosing and long-term effects are not known, it should probably be reserved for persons with moderate-to-severe disease. Dietary supplementation with oral indole-3-carbinol is often effective. Because of its adverse effects, treatment with interferon is now used infrequently as second-line therapy for patients with refractory severe disease. Control of gastroesophageal reflux is beneficial in children with RRP.

Dietary supplements

Certain types of vegetable extracts appear to improve symptoms.


Indole 3-carbinol (I3-C)

I3-C or its derivative, diindolylmethane (Indolplex), may be the active substance in cruciferous vegetables. I3-C changes the ratio of estradiol metabolites to the 2-hydroxyl derivative; this slows papilloma growth. Anecdotal experience demonstrates improvement in the disease with consumption of cabbage juice or a diet high in cruciferous vegetables (eg, cabbage, cauliflower, broccoli, Brussels sprouts). In clinical trials, one third of patients had a complete response and one third had a partial response to I3-C.

Adult

200 mg PO bid (Rosen and Bryson, 2003)

Pediatric

10 mg/kg PO qd

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include dizziness, headaches, unsteady gait, goitrogenic, and decreased bone density

Antiviral agents

Nucleoside analogs are phosphorylated initially by viral thymidine kinase to eventually form a nucleoside triphosphate and inhibit viral replication.


Cidofovir (Forvade, Vistide)

Currently approved for treatment of CMV retinitis in AIDS. First member of a group of antivirals known as acyclic phosphonate nucleotide analogs. In infected cells, nucleotide analogs such as cidofovir inhibit viral DNA polymerase, which is responsible for replication of new viral RNA and DNA. Because HPV is the causal agent for RRP, eradication of the virus offers the potential for cure. Small trials have reported that intralesional use is beneficial. In a prospective trial of 16 RRP patients, 77% of the 13 patients available for follow-up experienced remission of disease after an average of 3.5 injections.

Adult

Intralesional injection therapy under study: Reserve for moderate-to-severe disease requiring repeated interventions; recommendations regarding total dose to be administered intralesionally not established; concentration of 5 mg/mL used in 16-patient study noted above; patients were hydrated with normal saline prior to injection (Lee and Rosen, 2004); total dose in literature has varied from 2-54 mg (Shehab et al, 2005)

Pediatric

Not established; intralesional therapy dosing recommendations under study; 1 mg/kg recommended in one study (Chhetri and Shapiro, 2003)

With small amounts administered intralesionally, drug interactions may not be a problem; use of other potentially nephrotoxic drugs with IV cidofovir potentiates renal failure; other potentially nephrotoxic agents (eg, aminoglycosides, amphotericin B, foscarnet, NSAIDs, IV pentamidine, IV vancomycin); antiretroviral protease inhibitors increase risk of iritis or uveitis

Documented hypersensitivity; toxicity of intralesional cidofovir has not been fully established; renal impairment or renal failure defined as a serum CrCL >1.5 mg/dL; sensitivity to probenecid and sulfa-containing medications

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Intralesional administration probably is relatively nontoxic; when used IV, may cause renal toxicity, bone marrow suppression, and metabolic acidosis


Acyclovir (Zovirax)

Inhibits viral DNA synthesis. A synthetic deoxyguanosine analog and the prototype antiviral agent that is activated by viral thymidine kinase. In small numbers of patients, acyclovir started on the day of surgical resection appeared to slow the rate of regrowth of papillomas. Combined treatment with interferon may decrease the rebound regrowth sometimes noted with interferon discontinuation.

Adult

Specific dose recommendations for RRP not provided; in other viral illnesses, long-term suppressive dose is 400 mg PO bid

Pediatric

<2 years: Not recommended
<40 kg: 20 mg/kg PO bid
>40 kg: Administer as in adults

Probenecid decreases renal elimination and increases levels and potential toxicity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use with nephrotoxic agents increases risk of nephrotoxicity (eg, crystalluria, azotemia, renal failure)

Interferons

Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alfa, beta, and gamma interferons may be administered topically, systemically, and intralesionally.


Interferon alfa-2a (Roferon A)

Exerts antiviral effects by inhibiting translation of viral proteins. In the absence of an effective antiviral agent, use of drugs that augment host defense is a reasonable approach. Seventy-five to 80% of patients respond to interferon, with a complete response in approximately 30%. Does not eradicate the virus, and relapse may occur after discontinuation of treatment. Usually is administered for at least 6 mo in patients who require more than 3-4 surgical procedures each year. Case reports suggest that combined treatment with acyclovir or retinoic acid may be beneficial in patients with recurrent disease during interferon treatment.

Adult

5 million U/m2 SC qd for 1 mo, then 3 times/wk for 6 mo

Pediatric

Administer as in adults

Additive myelosuppressive effects with myelosuppressive agents; increases theophylline serum concentrations; increases risk of renal failure with aldesleukin and IL-2

Documented hypersensitivity, including hypersensitivity to benzyl alcohol (used as a preservative)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor blood counts and LFT results; associated with headache, malaise, leukopenia, thrombocytopenia, and hepatitis

More on Recurrent Respiratory Papillomatosis

Overview: Recurrent Respiratory Papillomatosis
Differential Diagnoses & Workup: Recurrent Respiratory Papillomatosis
Treatment & Medication: Recurrent Respiratory Papillomatosis
Follow-up: Recurrent Respiratory Papillomatosis
Multimedia: Recurrent Respiratory Papillomatosis
References
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Further Reading

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Keywords

RRP, juvenile-onset recurrent respiratory papillomatosis, JORRP, adult-onset recurrent respiratory papillomatosis, AORRP, human papilloma virus, HPV, human papillomavirus, airway obstruction, voice change, warts, sexually transmitted diseases, STDs

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Contributor Information and Disclosures

Author

Eloise M Harman, MD, Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine
Eloise M Harman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Medical Women's Association, American Thoracic Society, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School
Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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