What Are Treatments for Recurrent Respiratory Papillomatosis?

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Patient Presentation
A 4-year-old female came to clinic to establish care.
She was a healthy female except for a history of recurrent respiratory papillomatosis that was being managed by otolaryngology. She was noted to have laryngeal and proximal tracheal involvement. The past medical history showed that she had been diagnosed around 20 months of age after failed treatment for asthma and hoarseness. Initially she was managed with laryngoscopy and microblade excision but she had needed more frequent treatments and was also treated with human papilloma virus (HPV) vaccine. Over the past 6 months she has only needed 1 surgical treatment and was currently asymptomatic. Her family was well-aware of signs and symptoms that the papillomas were recurring and when this occurred she slowly developed a raspy voice. They denied any other papillomas on her body.

The pertinent physical exam revealed a healthy appearing female with normal vital signs and growth parameters in the 50-90%. Her overall physical and skin examination were normal.

The diagnosis of a healthy female with history of recurrent respiratory papillomatosis was made. The pediatrician discussed ongoing care including reviewing recommendations for repeated HPV vaccine when she turned 9 years old.

Discussion
Human papilloma virus (HPV) is a member of the Papillomaviridae virus family with over a 150 different subtypes. HPV can cause cervical, genital and respiratory tract papillomas. HPV is often benign but can cause anogenital, cervical and head and neck cancers.

Recurrent respiratory papillomatosis (RRP) is uncommon but can cause significant morbidity while awaiting the body’s immune system to respond. There is a juvenile and adult form, and the incidence varies between 2-4/100,000 in the pediatric population. The juvenile form frequently occurs between 3.6-6 years of age and in general the younger the patient, the more severe the disease.

The RRP papillomas are histologically benign, exophytic lesions occurring after the virus invades the epithelial keratinocytes but because of the location and increased recurrence risk, can lead to phonologic and respiratory problems which can be severe. The larynx (with the glottis, supraglottis and subglottis affected in this order) is always involved with trachea (3-26%), bronchi and distal lung structures (1-3%) decreasing in involvement. The esophagus can also be involved. RRP is most commonly caused by types 6 and 11 with type 11 having more severe disease, whereas the oncogenic serotypes are often 16, 18 and 33.

Transmission is thought to be mainly vertical transmission with exposure to maternal genital lesions. However, infants born by cesarean section can have RRP and the virus has been found in amniotic fluid and placenta. Cesarean section does decrease the risk of transmission though by > 4 times.

Patients commonly have hoarseness or stridor, and can also present with include wheezing, voice change, weak cry, chronic dyspnea, choking, or syncope. “Symptoms of hoarseness, cough, and dyspnea may be mistaken for diseases such as vocal nodules, allergic rhinosinusitis or asthma.” Therefore it is not uncommon that diagnosis is delayed as these entities are more common than RRP. RRP diagnosis is via laryngoscopy.

Learning Point
There is no cure for RRP but symptomatic management and trying to prevent recurrence or stimulate the immune system to control the virus. Treatment is primarily surgical debridement with a variety of laryngoscopy techniques with the potential risk of damaging of the structures and laryngeal scarring. Additional treatments are often tried when the number of debridements is around 4-6/year which include antiviral medications (e.g. cidofovir, acyclovir, ribavirin, ganciclovir, etc.), immune modulators (e.g. interferon, cetuximab, bevacizumab), and H2 receptor blockers (e.g. cimetidine).

HPV vaccine is also a possible treatment. HPV vaccine is usually given in the US at ages 9-26 in a 2 or 3 dose schedule. It is very effective and most effective in women who have not become sexually active. HPV vaccine use in the general population has been associated with a significant decrease in RRP. HPV vaccine when used as an additional RRP treatment has also shown to decrease recurrent RRP.

Questions for Further Discussion
1. How effective is HPV vaccine for prevention of cervical cancer?
2. What are the potential side effects of HPV vaccine?
3. What antiviral medication do you use in your practice?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: HPV and Throat Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Alfano DM. Human Papillomavirus Laryngeal Tracheal Papillomatosis. J Pediatr Health Care. 2014;28(5):451-455. doi:10.1016/j.pedhc.2014.04.003

Silva L, Goncalves CP, Fernandes AMF, Damrose EJ, Costa HO. Laryngeal papillomatosis in children: The impact of late recognition over evolution. J Med Virol. 2015;87(8):1413-1417. doi:10.1002/jmv.24181

Benedict JJ, Derkay CS. Recurrent respiratory papillomatosis: A 2020 perspective. Laryngoscope Investig Otolaryngol. 2021;6(2):340-345. doi:10.1002/lio2.545

Patel A, Orban N. Infantile recurrent respiratory papillomatosis: review of adjuvant therapies. J Laryngol Otol. 2021;135(11):958-963. doi:10.1017/S0022215121002322

Ponduri A, Azmy MC, Axler E, et al. The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis. The Laryngoscope. Published online January 18, 2023. doi:10.1002/lary.30560

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Published