Treatments: Laryngeal Papillomas (Recurrent Respiratory Papillomatosis)
Surgical removal, adjuvant medications, immune-based therapy, and long-term follow-up for a recurring airway condition
What is recurrent respiratory papillomatosis?
Recurrent respiratory papillomatosis (RRP) is a rare condition in which wart-like growths (papillomas) develop in the airway, most often on the vocal cords and voice box (larynx). It is caused by a long-lasting infection with the human papillomavirus (HPV), usually types 6 or 11. These growths can cause hoarseness, voice changes, and, when large, difficulty breathing. RRP can begin in childhood (juvenile-onset) or adulthood (adult-onset). A separate page describes the condition of laryngeal papillomas in more detail.
What are the goals of treatment?
There is currently no reliable cure that removes the underlying HPV infection in every person, so treatment focuses on several practical goals:
Keeping the airway open and breathing safe
Preserving and improving the voice (see also voice treatments)
Reducing how often the growths come back and how quickly they regrow
Limiting the number of procedures over time and the scarring they can cause
Maintaining quality of life
Because RRP tends to come back, care is usually ongoing and is tailored to disease severity, age, and how aggressive the growths are.
Surgical removal (debulking)
Surgical removal of the papillomas, often called debulking, has long been the mainstay of treatment. The aim is to clear enough of the growth to restore the airway and voice while protecting healthy tissue, since aggressive removal can cause scarring, webbing (bands of scar tissue), and permanent voice changes. Surgery is typically done in the operating room under general anesthesia, using a microscope and small instruments passed through the mouth. Several tools are used, and studies suggest they are broadly similar in controlling the disease, so the choice often depends on the location of growths, surgeon experience, and available equipment.
Microdebrider: A small powered suction-cutting device that shaves away growths. It is often quick and, in some studies, has been linked to shorter operating times and lower rates of scarring. It is a common choice, including for bulky disease.
CO2 laser: One of the earliest lasers used for RRP. It precisely vaporizes tissue but, in some analyses, has been associated with higher rates of scar and web formation compared with other methods.
Cold steel (traditional instruments): Removal using fine forceps and scissors without heat. This approach avoids heat-related tissue injury but has been used less in many centers because of concerns about voice outcomes; it remains preferred in some regions.
Pulsed dye and KTP (potassium-titanyl-phosphate) lasers: "Photoangiolytic" lasers that target the small blood vessels feeding the papillomas while sparing surrounding tissue. They are increasingly used, particularly in adults, and can often be used in the operating room or in the office.
Office-based procedures under local anesthesia
For some people, growths can be treated in the clinic while awake, using numbing medication rather than general anesthesia. These office-based procedures often use photoangiolytic lasers (such as KTP or pulsed dye) passed through a flexible scope (see fiberoptic laryngoscopy). Potential advantages include avoiding repeated general anesthesia, faster recovery, and treating disease earlier before it becomes bulky. Office-based treatment is generally used for less extensive disease in people who can tolerate an awake procedure.
Adjuvant therapies
Adjuvant therapies are added to surgery to help control disease and lengthen the time between procedures. They are generally considered when growths return frequently or spread. Their use and effectiveness vary from person to person.
Bevacizumab: A medication that blocks a growth factor (VEGF) the papillomas rely on for their blood supply. It can be injected directly into or near the lesions during surgery, or given through a vein (intravenously) for more aggressive or widespread disease. It has become one of the most promising add-on treatments, often prolonging the interval between surgeries. Because it treats the growths rather than the HPV infection, the disease can return after the medication is stopped. Possible side effects with the intravenous form include high blood pressure, protein in the urine, and nosebleeds.
Cidofovir: An antiviral medication injected into the lesions to interfere with viral replication. It has been used to extend the time between surgeries, though results are inconsistent. It is used less often now, and questions about its long-term safety have been raised.
Interferon: An older injected immune-modulating treatment. Early studies did not show durable control of the growths, and side effects limited its use, so it is now largely of historical interest.
HPV vaccination: Vaccines such as the 9-valent HPV vaccine (Gardasil 9) protect against HPV types 6 and 11, among others. While primarily designed to prevent infection, vaccination has been studied as an add-on in people with RRP and has been associated with longer growth-free intervals and, at a population level, a decline in new RRP cases.
Other approaches: Additional adjuvants that have been explored include coblation, cryotherapy, mitomycin C, photodynamic therapy, and indole-3-carbinol, with varying and often limited evidence.
Newer approaches: immunotherapy and gene therapy
A major shift in RRP care has been the development of treatments that target the underlying HPV infection by activating the body's own immune response against HPV-infected cells (see also chemotherapy and immunotherapy).
PRGN-2012 (zopapogene imadenovec; brand name Papzimeos): This is a gene therapy that uses a modified, non-replicating adenoviral vector to train the immune system to recognize and attack cells infected with HPV 6 and 11. It is given as a series of four injections under the skin over about 12 weeks, alongside surgical removal of visible growths. In its main clinical trial, about half of adults treated needed no further surgery to control their disease in the year after treatment, with responses lasting well beyond that in many cases; side effects were generally mild, such as injection-site reactions, fatigue, chills, and low-grade fever. It has been approved by the FDA for adults with RRP and is described in expert guidance as a leading first-line medical option for adults.
INO-3107: An investigational DNA-based immunotherapy that has shown reductions in the need for surgery in early studies and is under regulatory review.
Immune checkpoint inhibitors (such as pembrolizumab, a PD-1 inhibitor): These broadly activate the immune system and have shown encouraging early activity, but short courses have not been curative and they carry a risk of immune-related side effects.
The best way to sequence these newer treatments with established options such as bevacizumab is still being studied.
Tracheostomy considerations
A tracheostomy is a surgical opening in the neck into the windpipe to secure breathing. In RRP it is generally avoided whenever possible, because the airway opening and tube can be associated with the growths spreading further down into the trachea and lungs. Studies have linked tracheostomy, particularly when needed at a young age or for a long duration, with more severe disease, lower rates of remission, and worse outcomes, although this partly reflects that sicker patients are the ones who need it. When breathing is dangerously blocked and the airway cannot be maintained any other way, a tracheostomy can be lifesaving. In those situations, the general approach is to remove the tube as soon as it is safely possible.
Risks of treatment
Scarring and webbing: Repeated procedures on the delicate vocal cords can cause scar tissue and bands (webs), leading to permanent hoarseness or breathing narrowing.
Voice changes: Both the disease and its treatment can affect voice quality.
Anesthesia risks: Many people require multiple procedures over years, and each general anesthetic carries its own small risks.
Spread of disease: Instrumentation of the lower airway and tracheostomy can be associated with growths spreading downward.
Medication side effects: As noted above, adjuvant and systemic medications each have their own possible side effects.
Rare malignant change: In a small number of cases, papillomas can transform into cancer over time (see throat cancers), which is one reason ongoing monitoring matters.
Follow-up and surveillance
RRP is a chronic, recurring condition, and long-term follow-up is an important part of care. Growths most often return within the first year after surgery, but they can recur many years later, so being free of disease for several years does not necessarily mean a cure. Follow-up usually involves regular examination of the voice box with a scope (laryngoscopy), with the frequency guided by how active and aggressive the disease is. More aggressive disease, certain HPV types (such as HPV 11), disease that has spread beyond the larynx, and childhood onset are associated with more frequent recurrences and closer monitoring. Because rare malignant change is possible even in milder cases, surveillance is often long-term, sometimes lifelong. HPV type testing and imaging of the lungs may be part of contemporary evaluation in selected cases.
Key points
Surgery to remove the growths remains the foundation of care, with several comparable tools available; the goal is to protect breathing and voice while limiting scarring.
Adjuvant medications, especially bevacizumab, and HPV vaccination can help extend the time between surgeries.
Newer immune-based therapies, including the FDA-approved gene therapy PRGN-2012 (Papzimeos), target the underlying HPV infection and offer the possibility of durable control for adults.
Tracheostomy is generally avoided but may be necessary for airway emergencies.
Because RRP tends to recur, ongoing follow-up and monitoring are an important part of treatment.