In-depth and helpful information about RRP
About RRP
RRP can be a confusing diagnosis and disease. Our goal is to provide a community of comfort and crucial information to the RRP Community.
General RRP information
RRP may present at any age but there is a distinct preference to develop in children by the age of 5 (JORRP) and a broad secondary diagnosis preference seen in adults (AORRP) between the ages of 20 and 40. Most diagnoses involve HPV 6 or HPV 11. The connection between HPV and RRP was made in the early 1980’s.
Although there is still a lack of a comprehensive epidemiological database of RRP patient information, in 2020 the RRP Foundation partnered with RRP Patient Registry/CoRDS to initiate an international IRB reviewed, HIPAA/ GDPR compliant, RRPF Patient Registry.
The objective of this registry is to find answers to many outstanding RRP epidemiological questions, gain a true natural history from diagnosis to death to better drive research, as well as coordinate patient-centric RRP research.
How common is RRP?
One of the first estimates of RRP incidence and prevalence in the U.S. was based on a study conducted in 1995 by the RRP Task Force. Their projected totals for recurrent respiratory papillomas among children were 2354 new cases per year, with a 95% confidence interval (CI) ranging from 1448 to 3260, and 5970 active cases, with a 95% CI ranging from 3465 to 8474. The projections for AORRP were 3623 new cases per year (95% CI, 2359 to 4887) and 9015 active cases (95% CI, 6435 to 11,591). These estimates indicated an incidence among children of about 4.3 per 100,000 and among adults of about 1.8 per 100,000. A comprehensive study looking at 1994-2007 data from the Canadian national JORRP registry (Campisi et al., 2010) indicates JORRP incidence of .24 per 100,000 and prevalence of 1.11 per 100,000.
We are recently making exciting progress on lowering the incidence rate of RRP since the introduction of the HPV vaccine (Gardasil). For JORRP, Australia has lowered their incidence rate to 0.022 per 100,000 in 2016, and in 2019 no new cases of JORRP were reported(Novakovic et al). In the United States, the JORRP incidence rate is most recently considered to be 0.5 per 100,000.
What are the risk factors for RRP?
There is considerable evidence that RRP in children results from a vertical transmission of HPV from mother to child. Virology studies have substantiated the link between genital condylomas and JORRP. HPV types 6 and 11, which are responsible for 80-90% of the condylomas, are responsible for nearly 100% of JORRP.
“Multiple studies have shown that the most likely route of transmission of HPV in RRP is from mother to child during labor. Exceptions to this may include patients with congenital RRP who have been exposed in utero and adult patients who may have been exposed during sexual contact. Although cesarean section may prevent the exposure of children to the HPV virus during childbirth, its effectiveness in preventing RRP is debatable and the procedure itself carries an increased risk of complications.”
Cesarean section as a preventative measure is not the standard of care, unless active disease is present, and even then it may not be preventative.
Adult onset of RRP is also caused by infection with HPV-6 and HPV-11. However, there does not appear to be a statistically significant relationship with birth factors as is seen in JORRP cases. This probably indicates that for AORRP, the infection is not likely acquired at birth and there is some speculation that for many adults it may be sexually transmitted. There is also speculation that in some AORRP patients, it could possibly be dormant disease from childhood/infancy that never manifested as active disease.
Why does RRP occur?
Beyond the previously noted risk factors regarding the transmission of HPV, it is still not very well understood why only certain individuals present with RRP. It is estimated that approximately 5% of the U.S. population may have HPV in their respiratory tract, but less than 1 in 1000 of those infected ever develop RRP. This seems to invite the speculation that some subtle immunologic deficiency affects the respiratory tracts of those few who develop RRP. A clearer understanding of whether RRP lesions harbor genomic alterations similar to malignancies that could render populations of cells resistant to T cell recognition may inform future immunotherapy (non-surgical options) strategies. (Dr. Clint Allen-NIH)
The introduction of the HPV vaccine (Gardasil), is helping to lower the incidence of RRP, especially in those countries where mandatory vaccination is required.
What Are The Symptoms Of RRP?
The most common symptom of RRP is a voice that is persistently hoarse, weak, low in pitch, breathy, or strained, as well as a chronic cough. Often dysphonia (i.e., difficulty in speaking) or aphonia (i.e., loss of voice) can occur as well. Tumor mass and location (i.e., how the growths interfere with normal vocal cord function) may explain the degree of voice quality defects. For lesions that form near the vocal folds, hoarseness can occur very quickly with small lesions. As the disease progresses, shortness of breath can occur as the airway becomes blocked by bulky lesions.
Although this is more common in children, in some situations RRP can cause breathing difficulties in adults, especially during exercise. Young children often present with a weak cry, chronic cough, swallowing difficulties and stridor. Inspiratory stridor is noted by noisy breathing such as a high-pitched whistle or snore as a child strains during inhalation, usually as they sleep. This is indicative of an upper respiratory obstruction and warrants immediate attention by an otolaryngologist. RRP related symptoms may develop gradually over months or even years in mild cases, but in very aggressive situations symptoms may emerge in a matter of days, even if the patient has recently had a surgical procedure to remove disease.
How is RRP diagnosed?
RRP is typically diagnosed by an ear, nose and throat physician (ENT) performing an examination of the larynx. Some physicians may start with a mirror examination, which is done using a mirror placed in the back of the throat reflecting light down the throat and onto the vocal folds. More typically a doctor or a trained speech-language pathologist diagnoses RRP via an indirect laryngoscopy in the ENT office. This involves the placement of a flexible fiberoptic camera through the nose to further visualize the vocal folds in the throat or the use of a straight, rigid camera placed through the mouth that shines down the throat onto the vocal folds. In addition to allowing the ENT to view the larynx, a video record can also be obtained with these instruments. Some otolaryngologists or speech pathologists may use a videostroboscopy to obtain an even more detailed look. However, to make an absolutely definitive diagnosis of RRP a direct laryngoscopy (usually in conjunction with surgical removal of papilloma growths) must be performed in an operating room with the patient under general anesthesia at which time a biopsy is taken and tested for HPV.
For a small percentage of RRP patients papilloma may progress deep in the respiratory tract into the lungs. Currently there is no standard protocol for diagnostic/screening CT scans of RRP patients, unless there are symptoms of pulmonary distress. More information about pulmonary RRP can be found on the RRPF Pulmonary RRP page.
In some cases the direct laryngoscopy is the only option, usually this involves young children in distress, where instrumenting the airway outside of the operating room might be hazardous. It is most desirable, however, to have a diagnosis of RRP before a surgical procedure so as to facilitate family awareness/expectations so the anesthesiologist, surgeon and OR nurses will be properly prepared. Pediatricians who are unfamiliar with this disease often misdiagnose RRP. Many times shortness of breath and stridor are mistakenly assumed to be the result of asthma or croup. The consequences of these errors may be serious as papillomas are at least partially obstructing the airway to cause these symptoms and should be removed immediately.
When RRP is suspected as a possibility it is important to find a doctor who has RRP expertise. The RRPF maintains a database of RRP practitioners that we have found to be experienced in the care of patients with RRP.
If RRP is suspected, it is important to verify that PCR testing will be done on the tissue to determine specific HPV type. Based upon recent reports regarding type and distal spread, if a patient is typed as HPV11, there is data indicating a more severe disease course, as well as a higher risk of distal spread/pulmonary spread.
Is RRP contagious?
Recurrent Respiratory Papillomatosis is not a shareable disease based upon current research, unlike oral HPV.
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