Recurrent Respiratory Papillomatosis Treatment & Management

Updated: Dec 14, 2020
  • Author: Eloise M Harman, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Treatment

Approach Considerations

There is no curative therapy for recurrent respiratory papillomatosis (RRP). 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. Six months of subcutaneous interferon therapy may be beneficial but there is controversial evidence regarding clinical efficacy. [21]

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Medical Care

Pharmacotherapy

Because recurrent respiratory papillomatosis (RRP) 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. The use of intralesional cidofovir in moderate-to-severe disease has been a major advance in the management of RRP. It is indicated if surgical debulking is required 6 or more times per year or every 2-3 months, and its administration must be guided by knowledge of safe dosing limits. [22]

With the increased use of intralesional cidofovir and because of its adverse effects, treatment with interferon is now used infrequently as second-line therapy for patients with refractory severe disease.

Bevacizumab, a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor in vitro and in vivo, by preventing receptor activation. Based on the evidence that vascular endothelial growth factor is an important factor in the development of RRP, there have been reports of promising results achieved with bevacizumab. [23] This adjuvant therapy could increase the time interval between surgical procedures, with a simultaneous reduction in number of procedures required per year; improvements in voice quality may also be achieved.

Vaccination

A quadrivalent vaccine for prevention of genital human papillomavirus (HPV) infection was approved in 2006. This vaccine protects against HPV types 6, 11, 16, and 18 and has promise for decreasing the incidence of RRP. [24, 25] (See Epidemiology.)

Vaccine therapy for those already affected with HPV has been reported in the literature. A study by Hočevar-Boltežar and colleagues pointed out that vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with rapid growth of papillomas by significantly prolonging intervals between surgical procedures and reducing of the number of procedures needed in the majority of patients observed. [26]

Chirila et al concluded that the quadrivalent HPV vaccine was effective to diminish the recurrence rate of RRP in 85% of patients, although that study was retrospective and lacked a control group. [27]

Another retrospective chart review also assessed the effect of quadrivalent vaccine on the disease course of RRP. Analysis was conducted on 20 patients receiving the vaccine; intersurgical interval (ISI) before and after vaccination and the number of remissions (both partial and complete) were described. Complete or partial remission was achieved in 65% of patients; an ISI increase of 4.2 months was noted in males (95% CI: 1.6-6.7, P = 0.0048) while a nonsignificant ISI increase of 1.2 months was noted in females (95% CI: 3.1-5.4, P = 0.51). [28]

In a small retrospective observational study of the impact of the quadrivalent HPV vaccine on the immune status of patients with recurrent respiratory papillomatosis, Pian et al found that mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (P <  0.001). In addition, the mean number of surgical interventions in a specific time frame after vaccination decreased with approximately a factor of 3.3. [29]

Although promising, these isolated positive experiences need to be validated by multicenter trials that might be able to ascertain the true benefits of vaccination as a treatment of RRP.

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Surgical Care

Multiple resections are typical. Microdebridement of laryngeal lesions is often preferred to laser therapy in the treatment of recurrent respiratory papillomatosis (RRP). 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.

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Prevention

In 2006, a vaccine was released that protects against human papillomavirus (HPV) types 6, 11 (associated with venereal warts), 16, and 18 (associated with cervical cancer). Administration to girls before they become sexually active is expected to be highly effective in preventing HPV infection and resultant venereal warts and would be expected to lead to a future reduction in JORRP incidence. [24]

Two additional strategies have been proposed to have more direct effects on JORRP incidence [30] :

  • Vaccination of neonates born to women with clinically diagnosed genital warts

  • Vaccination of pregnant women infected with HPV 6/11, to boost maternal titers of neutralizing antibody and increase maternal transfer of antibody to the newborn.

The role of cesarean delivery in the prevention of JORRP is controversial because the disease is quite uncommon, despite the frequency of genital HPV infection. Consider cesarean delivery in a young woman with visible condylomata who is giving birth to her first child. [2]

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