Recurrent Respiratory Papillomatosis

Updated: Dec 14, 2020
  • Author: Eloise M Harman, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Recurrent respiratory papillomatosis (RRP) is a disease caused by the human papillomavirus (HPV). See Human Papillomavirus and Medscape’s HPV and Cervical Cancer Resource Center for more information on HPV. Warty growths in the upper airway may cause significant airway obstruction or voice change. [1] RRP has a bimodal age distribution and manifests most commonly in children younger than 5 years (juvenile-onset RRP [JORRP]) or in persons in the fourth decade of life (adult-onset RRP [AORRP]).

Respiratory papillomatosis is shown in the image below.

A 48-year-old woman presents with inspiratory stri A 48-year-old woman presents with inspiratory stridor, dyspnea, and hoarseness. On direct laryngoscopy, extensive respiratory papillomatosis were diagnosed as the cause of her symptoms. Courtesy of Sat Sharma, MD, and L. Garber, MD.

JORRP is more common and more severe than AORRP. JORRP is caused by exposure to HPV during the peripartum period. The mode of infection in adults is still not known, but sexual transmission is likely.

Treatment usually involves repeated debulking of the warty growths by angiolytic laser or microdebridement coupled with intralesional cidofovir therapy in patients with moderate or severe disease. Interferon treatment appears to slow the rate of growth without curing the disease. Although some antiviral agents (eg, cidofovir) also may slow the rate of regrowth of lesions, they are not curative. Eventually, some patients may enter remission. In 3-5% of patients, respiratory papillomas may undergo malignant degeneration to squamous cell carcinoma, and the prognosis for patients with these cancers is quite poor. See Squamous Cell Carcinoma for more information on this topic.



Human papillomavirus (HPV), the virus associated with cutaneous warts, genital condyloma, and cervical cancer, causes recurrent respiratory papillomatosis (RRP). While more than 20 types of HPV can cause genital warts, only two of these, HPV-6 and HPV-11, cause the vast majority of cases of RRP. The disease associated with HPV-11 is more severe; thus, in children with HPV-11–associated disease, as many as 70% may require tracheostomy, compared with less than 20% of children infected with HPV-6 (see Human Papillomavirus).

The cause of JORRP is peripartum transmission of the virus from an infected mother. Vaginal delivery is a risk factor, but cesarean delivery is not completely protective. [2] The classic triad for increased risk of JORRP includes being firstborn, vaginal delivery, and having a mother younger than 20 years. [3, 4] Lower socioeconomic status is also a risk factor. Suspect sexual abuse in children older than 5 years who acquire RRP. The mode of transmission of the virus in adults with RRP is unknown, but sexual transmission is probable as risk factors in adults include more lifetime sexual partners and increased frequency of oral sex as compared with controls. [5]

Papillomas may develop anywhere in the respiratory tract, from the nose to the lung; however, >95% of cases involve the larynx. The sites of respiratory system involvement have been described more completely for JORRP; 52% of children have only laryngeal involvement. The trachea is the next most commonly involved site. However, 31.8% of children had papillomas in areas outside of the trachea and larynx (eg, oropharynx, nasopharynx, mouth, bronchi, lung parenchyma).



Human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). HPV-6 and HPV-11 are the most common types associated with RRP, but, rarely, affected tissues contain HPV-16 and HPV-18. HPV is the most common sexually transmitted disease in the United States; as many as 75% of women have genital HPV at some time in their lives. Thirty to 60% of mothers of children affected with JORRP have genital HPV, compared with 5% of mothers of unaffected children. A study using questionnaires of affected children or their parents (identified through the RRP Foundation) verified that the 3 risk factors for JORRP are (1) firstborn child, (2) vaginal delivery, and (3) mother younger than 20 years. The risk factors for JORRP do not apply to adult-onset cases. This suggests that adult disease does not represent reactivation of latent disease. The mode of transmission of HPV in AORRP is not known. Sexual transmission is likely.



United States data

Prior to the introduction of a quadrivalent vaccine for prevention of genital HPV in 2006, the estimated incidence of recurrent respiratory papillomatosis (RRP)in the United States was 4 per 100,000 in juvenile‐onset RRP (JORRP) and 2 per 100,000 in adult–onset RRP (AORRP). [6] RRP is declining in incidence; however it remains the most common benign laryngeal neoplasm in children. [7, 8] Roughly 15,000 surgical procedures for the condition are performed each year, at an estimated cost of $100 million. [9]

International data

A study by Donne et al estimated the prevalence of patients with recurrent respiratory papillomatosis in the United Kingdom to be 1.42 per 100,000. [10]

Australia introduced a nationwide immunization effort in 2007 which provided the HPV vaccine to at least half of all females aged 12-26. [11] The Australian National Immunisation Program began providing immunizations to all students aged 12-13 years (girls in 2007 and boys in 2013) through a school-based initiative. As a result, the incidence of HPV in women 18 to 24 dropped from 22.7% in 2005 to 1.1% in 2015. [12] The incidence of JORRP declined to 0.022 per 100,000 in 2016. [11]

Race-, sex-, and age-related demographics.

The National Registry for Juvenile-Onset Recurrent Respiratory Papillomatosis, [13] a registry including 603 children from around the United States, reports that 63% of the children were white, 28.4% were black, 0.8% were Asian, 0.8% were Native American, and 7% were unknown. Ethnicity was reported for 367 (60.9%) of the patients; 57 (15.5%) were identified as Hispanic and 310 (84.5%) as white or black non-Hispanic. [13]

JORRP affects males and females in equal numbers, whereas AORRP is more common in males.

The mean age at diagnosis of JORRP is 3.1 years. [13] The adult form usually manifests in the third or fourth decade of life but may rarely manifest in patients older than 60 years. [14]



Children with recurrent respiratory papillomatosis (RRP) frequently experience remission after several years, which may be related to puberty. By this time, the patient may have undergone more than 20 surgical procedures. Younger patients with HPV-11 etiology experience a worse clinical course. Disease in adults tends to be milder; however, older patients with an HPV-6 etiology experience a worse clinical course. [15]

Because the disease is uncommon and requires direct laryngoscopy for diagnosis, children usually have symptoms for a year before a physician makes the diagnosis. The morbidity of this disease has been studied more completely for JORRP, in which the average number of surgical procedures required is 4.4 per child per year and the average number of procedures per child's lifetime is more than 20. [16] This exacts a tremendous financial cost and severely affects quality of life, including the ability to attend school and work. Ten to 15% of children with JORRP ultimately require tracheostomy, usually when younger than 2 years. Many eventually tolerate decannulation.

The need for tracheostomy in adults appears to be less common than in children, but repeated surgical procedures are the rule, and procedures may be required as often as every few weeks.

Malignant degeneration of papillomatous lesions to squamous cell carcinoma occurs in 3-5% of patients with RRP. The prognosis for squamous cell carcinoma in the context of RRP is grave. Cure is uncommon.


Complications of this disease include airway obstruction and malignant transformation.

With regard to tracheostomy, older literature suggests that in RRP patients, it may promote distal airway spread (ie, distal to the larynx) of papillomas. A more recent review suggests that patients who require tracheostomy tend to present at a younger age with more severe disease that already involves the more distal airway. Distal spread after a tracheostomy most commonly involves the tracheostomy site. After laser and antiviral treatment over a period of years, the tracheostomy often can be removed successfully; therefore, tracheostomy is a reasonable option if required due to significant airway obstruction. [17]  The need for tracheostomy probably is a marker of more severe disease rather than an independent cause of distal spread.

Malignant degeneration of papillomatous lesions to squamous cell carcinoma occurs in 3-5% of patients with RRP. Distal airway spread of papillomas often is a forewarning of malignant degeneration. The site of malignancy in JORRP usually is the bronchial or pulmonary parenchyma, whereas the larynx is the usual site in AORRP. Malignant degeneration is more common with disease caused by HPV-11 and HPV-16. Cigarette smoking, bleomycin therapy, and radiation treatment of involved areas also increase the risk of malignant degeneration in RRP.


Patient Education

Recurrent respiratory papillomatosis (RRP) usually is a pediatric disease. The main problem is recurrent airway obstruction. Teach parents to recognize potential warning signs, including a weak cry, hoarseness, stridor, wheezing, cyanosis, and decreased exercise tolerance. Airway obstruction may recur as soon as 2-4 weeks after laser procedures, and recognizing its development before critical, life-threatening obstruction occurs is important.

RRP can be devastating to individuals and families. Children with JORRP may require repeated surgery and can be ill for a long time. The RRP Foundation may provide group support for individuals and families.

For patient education resources, see the patient education article Bronchoscopy.