A disorder in which wart-like tumors or other lesions grow recurrently within a person’s airway. These growths are caused by the human papillomavirus (HPV), and they may occur anywhere in a person’s airway, such as on the vocal cords (by far the most common site), in the supraglottic larynx, or in the trachea. If these growths are removed, they will almost always grow back, or recur; hence, “recurrent respiratory papillomatosis.”
Symptoms and risks of recurrent respiratory papillomatosis:
RRP can be life-threatening in young children, if not carefully followed and treated, since a child’s airway is relatively narrow and can potentially be obstructed completely by the disease’s proliferative growths; moreover, RRP in children tends to grow and recur more aggressively. In adults, RRP will usually only impair voice function (when the growths occur on the vocal cords), though it can also impair breathing in severe cases. Occasionally, RRP can also progress to cancer, and therefore patients found to be at high risk for this (see below) need to be monitored carefully.
Characteristics of the growths:
The growths usually associated with RRP are wart-like tumors, or papillomas, that protrude conspicuously from the surface on which they grow, often in grape-like clusters. These kinds of papillomas are usually seen in patients who have HPV subtypes 6 or 11, which are both lower-risk subtypes for incurring cancer. There are some HPV patients, however, who manifest their HPV infection with subtler, velvety growths within the airway—“carpet-variant” growths, so to speak. Although these “carpet-variant” growths do not have the wart-like appearance of the papillomas typically associated with RRP, there at least a few key points of similarity:
- Both the “carpet-variant” and wart-like growths are lesions that sometimes appear, either independently or together, in patients who have HPV;
- Both the “carpet-variant” and wart-like growths are stippled with polka-dot vascular markings, because each “loop” in the “carpet” or each “grape” in the wart-like cluster has its own fibrovascular core, seen as a red dot;
- Both the “carpet-variant” and wart-like growths can disrupt voice function;
- Both the “carpet-variant” and wart-like growths usually recur if they are removed.
Because of these similarities, we consider these “carpet-variant” growths, even when the sole expression of the infection, to be at least a cousin to RRP, within the family of HPV-induced lesions. Many patients with this “carpet-variant” condition have HPV subtypes such as 16 or 18 that are higher-risk for cancer; such patients need to be monitored with particular care.
Treatment for recurrent respiratory papillomatosis:
The primary treatment for RRP and other HPV-induced lesions is careful, conservative surgical removal of the growths. Because these growths almost always recur, surgery must usually be performed on a repeated basis, as frequently as every few weeks in children, but on average much less often in adults. A common interval between surgeries for adult patients is between every six months and every two years, depending on how quickly the RRP or other HPV-related lesion recurs and impairs the patient’s voice function again. There are also a few medical treatments that have been used in addition to surgery, including, among others, interferon, indole-3-carbinol, intralesional mumps or MMR (measles-mumps-rubella) vaccine, cidofovir, and bevacizumab.
Papillomas: HPV Subtype 11 (1 of 4)
Papillomas at posterior vocal cords, with left side (right of image) much larger than right. This patient has HPV subtype 11.
Papillomas: HPV Subtype 11 (2 of 4)
Closer view, under narrow band illumination, which accentuates the vascular pattern.
Papillomas, removed: HPV Subtype 11 (3 of 4)
Two weeks after microsurgical removal, cidofovir injection, and return of normal voice.
Papillomas: HPV Subtype 6 (1 of 4)
Papilloma, left vocal cord (right of image), standard light. Voice is grossly hoarse. This patient has HPV subtype 6.
Papillomas, removed: HPV Subtype 6 (3 of 4)
After removal and cidofovir injection, normalized larynx. Voice is normal.
Papillomas: HPV Subtype 11 (1 of 3)
Panoramic view, standard light, shows papillomas on the aryepiglottic cord, false cords, anterior face of arytenoid, and at anterior commissure. This patient has HPV subtype 11.
Papillomas: HPV Subtype 11 (2 of 3)
Closer view, standard light, shows more clearly the papillomas on the anterior face of the right arytenoid and at the anterior commissure.
Lesions of HPV Subtype ? (1 of 2)
Under standard light, faint stippled vascularity is seen, along with a general mild inflammatory response (pinkness). Patients like this are often misdiagnosed with acid reflux.
Lesions and papillomas of HPV subtype ? (1 of 8)
At initial diagnosis, as yet untyped for HPV. Multi-focal lesions on both vocal cords.
Lesions and papillomas of HPV subtype ? (2 of 8)
Narrow-band illumination and a different viewing angle better reveal the more subtle lesion on the upper surface of the right cord (dotted circle).
Lesions and papillomas of HPV subtype ? (3 of 8)
Strobe light, open phase of vibration, showing mismatch.
Lesions and papillomas of HPV subtype ?, 1 week after removal (4 of 8)
One week after removal of papillomas, voice is dramatically restored. Strobe light, open phase of vibration. Compare with photo 3.
Lesions and papillomas of HPV subtype ?, 1 week after removal (5 of 8)
Strobe illumination, closed phase. Even in falsetto, oscillatory ability is preserved due to the precise and superficial removal of the papillomas.
Lesions and papillomas of HPV subtype ?, injecting adjuvant (6 of 8)
At three weeks after removal, the patient regards his voice as normal. The patient has neither lesion nor vascular change to suggest any residual or recurrent lesion. Needle in photo (arrow) positioned to inject adjuvant medication in attempt to prevent recurrence. This procedure is done in a voice lab under topical anesthesia, not the operating room.
Lesions and papillomas of HPV subtype ?, after injecting adjuvant (7 of 8)
After both cords have been “inflated” with adjuvant medication. Note the convex, slightly blanched vocal cord margins, due to superficial infiltration of the medication.
Lesions and papillomas of HPV subtype ?, after final adjuvant injection (8 of 8)
Nearly a month later, immediately after the third and final adjuvant injection (hence the blood below the vocal cords). The patient again regarded his voice as completely normal. No sign at this early point of recurrence of papillomas or other HPV lesions. Patients with focal disease as seen in photo 1 of this series not infrequently go into long-term remission or “cure,” though it may be impossible to discern the relative roles of surgery, adjuvants, and the patient’s immune system.
Papillomas: HPV Subtype 55 (1 of 4)
Papillomas of the vocal cords, in a patient with HPV subtype 55, which is intermediate-risk for progressing to cancer.
Papillomas: HPV Subtype 55 (2 of 4)
Same exam, with narrow-band lighting, which accentuates the vascular pattern of the papillomas.
Papillomas, in remission: HPV Subtype 55 (3 of 4)
Same patient, years later, in remission, and with normal voice. No sign of papillomas here or anytime during the prior three and a half years, after meticulous removal and Cidofovir treatment.
Papillomas: HPV Subtype 11 (1 of 2)
Vocal cords, narrow band light, showing papillomas on the upper surface of the anterior vocal cords. This patient has HPV subtype 11.
Papillomas: HPV Subtype 31 (1 of 4)
Standard light, showing lesions on the vocal cords, in particular the stippled vascular pattern we call "HPV effect." The patient's voice was nearly gone, with numerous syllable drop-outs and a very effortful quality. Compare with photo 3.
Papillomas: HPV Subtype 31 (2 of 4)
Closer view, using narrow-band light to accentuate the vascular pattern of "HPV effect." Biopsy and additional testing of these lesions showed squamous papilloma with moderate dysplasia, and HPV subtype 31 was confirmed, which is high risk for eventually causing cancer. After the patient underwent several injections of cidofovir, the lesions persisted but seemed to become more indolent. On compassionate grounds, this fairly young person was then prescribed celecoxib for six months.
Papillomas, in remission: HPV Subtype 31 (3 of 4)
Three years after photos 1 and 2, standard light view. Within two months of the start of celecoxib, voice improved very noticeably, and the "HPV effect" vascularity resolved. Still, it is unknown what roles in this recovery were played by the patient's immune system, the cidofovir, and the celecoxib, respectively.
Obvious lesion not important (1 of 3)
Several months after removal of exuberant papillomas, voice remains quite good, but is becoming a little deeper. The obvious lesion here is not important; the subtle one is the key.
Granuloma (2 of 3)
Narrow band light reveals the spherical lesion to be a granuloma, not papilloma (which would have stippled vascular markings).
Papillomas: HPV Subtype 18 or 45 (1 of 2)
Papilloma growths on the right vocal cord (left of image), standard light. This patient's papillomatosis is caused by HPV, narrowed down to either subtype 18 or 45.
Lesions of HPV Subtype 16 (1 of 3)
Recurring inflammatory and leukoplakic lesions caused by HPV subtype 16. A left vocal cord cancer (right of image) was removed several years earlier, and the patient developed a right vocal cord cancer almost a year later.
Lesions of HPV Subtype 16 (2 of 3)
Slightly magnified view, focusing on the anterior (frontward) ends of the vocal cords. The cords' stippled vascularity, which often accompanies HPV infection, is more apparent here.
Cancer: HPV Subtype 16 (1 of 5)
Cancer, in a patient with HPV subtype 16. The divot and blood seen on the left vocal cord (right of image) are the result of a biopsy performed elsewhere (not by BVI physician) earlier the same day as this examination.
Cancer: HPV Subtype 16, after radiation therapy (3 of 5)
Six weeks after the end of radiation therapy, the tumor is no longer seen. However, part of the left cord (right of image) is missing, due to sloughing of the tumor that had eaten away part of the cord’s normal tissue.
Cancer: HPV Subtype 16, after radiation therapy (4 of 5)
Phonation. Strobe light, open phase of vibration, shows that the margin of the left cord (right of image) is at a lower level than the right’s, due to loss of some of the bulk of the cord where the tumor died and sloughed away.
Papillomas: HPV Subtype 45 (1 of 2)
Papillomas in the supraglottis, left of image. The pink, velvety area of papillomas is outlined by small arrows.
Mid-tracheal papilloma, being treated by thulium laser (1 of 5)
The papilloma is seen attached to the posterior tracheal wall, at the midpoint of the trachea. Note the areas of scarring from prior laser procedures. The dots seen indicate reference points for photo 5.
Mid-tracheal papilloma, being treated by thulium laser (2 of 5)
Using the channel scope, a blue glass fiber is extended from the tip of the scope.
Mid-tracheal papilloma, being treated by thulium laser (3 of 5)
In a closer view, the papilloma has been mostly cauterized using near-contact (not touching) mode.
Mid-tracheal papilloma, being treated by thulium laser (4 of 5)
The papilloma is then penetrated multiple times to deliver laser energy to its base. Some of the papilloma is pulled off by attachment to the fiber, and the remainder will slough off and be swept upwards by the mucociliary blanket (thin layer of mucus being swept upward) within the trachea.
Subtle papillomas, HPV subtype 6 (1 of 3)
After achieving a normal voice through several procedures, the patient came in for reexamination due to the return of mild huskiness. This distant panoramic view with standard illumination does not reveal any obvious papillomas.
Subtle papillomas, HPV subtype 6 (2 of 3)
At close range, using narrow band illumination, a subtle but definite HPV effect is seen. Notice the stippled vascular markings and the faintly increased pinkness at the margins of the cords, indicated by dotted lines.
Two papillomas (1 of 3)
Approximately one month after removal of papillomas and Avastin injection in a man who has battled aggressively-recurring disease caused by HPV, type 6. In this view using narrow band light, only two small papillomas are visible.
Stippled vascularity (2 of 3)
At closer range, careful inspection shows no papilloma (yet), but only the stippled vascularity typical of HPV infection.
Papilloma finding (1 of 4)
This young man had a tonsil problem and normal voice but during the initial head and neck examination was found to have a papilloma in his larynx. Rapid recurrence and spread triggered referral. Note stippled vascularity on masses along the edges of the false vocal cords.
Closed phase (3 of 4)
Under strobe light, closed phase of vibration, the true cords are seen to be uninvolved, and this explains his normal voice.
Left vocal cord lesion (1 of 8)
Middle aged woman with a 6-month history of hoarseness. Note the left vocal cord lesion (right of photo at arrow).
Narrow band light (2 of 8)
At closer range under narrow band light, the stippled vascular pattern suggests that this is HPV-related papilloma. Very tiny secondary lesions may be present at the arrow and ?
One week after removal (3 of 8)
A week after removal (and proof of HPV subtype 6), the left cord (right of photo) shows expected pinkness. The tiny lesion under the right cord (left of photo) “escaped” and appears larger but is still not a verifiable papilloma, nor is the tiny lesion on the upper surface of the right cord (left of photo) at the ?
2 months after removal (4 of 8)
Now 2 months after surgical removal of the original left cord lesion, that cord is healed and without evidence of papilloma. Voice is excellent—can pass for normal—but the tiny lesions previously seen are now verifiably flat papillomas (see stippled vascularity at arrows).
7 months after removal (5 of 8)
Now 7 months after original surgery, voice remains “almost” normal to the patient. Cord margins match well with voicing. Irregular margins are primarily due to overlying mucus.
Papilloma and mucus (6 of 8)
With abduction of the cords for breathing, a papilloma is seen below the margin of the right cord (left of photo at large arrow); the small arrows outline a peculiar “elevated” area that looks to be more than mucus the mucus seen at 'X'.
Stippled vascularity (7 of 8)
At closer range, under narrow band light, the stippled vascular marks further define the papilloma. Note normalized vasculature on the left cord (right of view) where the original papilloma was found. The “battle” of the left cord (right of photo) may have been won…
Papilloma (1 of 8)
Papilloma on right vocal cord (left of photo), proven by biopsy elsewhere. The disease has both a projecting component along with 'carpet-variant' component seen only via stippled vascular marks (within dashed line).
Stippling (2 of 8)
Closer view under strobe light; stippling is seen more clearly. Compare the stippling with the linear capillaries of the opposite cord.
One week after surgical removal (3 of 8)
One week after removal and sub typing (HPV 6) and cidofovir injection. Under narrow band light there is residual bruising but no significant stippling.
Cidofovir injection (4 of 8)
At final office-based cidofovir injection. Blood from the injection is seen, but still no stippling.
Six months after surgical removal (5 of 8)
Six months after removal, papillomas have recurred at the margin of the vocal cord, but not on its upper surface where linear capillaries have replaced stippling.
One week after second removal (6 of 8)
A week after second removal of papillomas and cidofovir injection, with expected inflammation, but no visible remaining stippled vascularity.
4 months later, healed (7 of 8)
4 months later, the vocal cord has long since healed and narrow band light is used to accentuate capillaries. No HPV effect (stippling) is seen.
Chronic hoarseness (1 of 4)
Chronic hoarseness, due to these papillomas, subsequently proven to be caused by subtype 6. Note HPV-effect vascularity.
4 months later (2 of 4)
A second surgery, 5 cidofovir injections (3 in office), and 4 months later, neither papilloma nor HPV vascular effect are seen here, under narrow band light.
8 months from start of treatment (3 of 4)
Now 8 months from the start of treatment, and 5 months since the final (office) cidofovir injection, there remains no evidence of abnormality. This view is under standard light.
"Polyps" diagnosis (1 of 4)
This patient is representative of persons initially diagnosed with "polyps," based upon a view like this one.
Papillomas (2 of 4)
Now we can see that these lesions are papillomas by the powerful visual criterion of vascular stippling aka "HPV vascular effect." Another clue of incorrect diagnosis, even with a distant view, would be the patient's non-match with the vocal overdoer syndrome.
Vascular stippling (3 of 4)
Narrow band light at the same magnification accentuates the vascular stippling. Typical papillomas indicated by arrows, and faint lines online areas of "carpet variant" papillomas.
Chronic hoarseness (1 of 6)
In this distant view, the nature of the abnormality of the right vocal cord (left of photo) is not well seen, and the lesion of the left posterior cord (right of photo) is subtle.
Narrow band light (2 of 6)
Under narrow band light, the two discrete lesions are better identified as being papillomas due to the punctate (dotted) vascular markings.
Higher magnification, narrow band lighting (4 of 6)
Back to narrow band light, to more carefully scrutinize the anterior right vocal cord lesion (left of photo).
Post-operation (5 of 6)
18 months after surgical removal and cidofovir injection, voice is excellent and there is no sign of recurrent papilloma.
Infiltrating anesthetic (1 of 3)
A 27-gauge needle tip is poised to infiltrate local anesthetic lidocaine with epinephrine into the papillomas (within dotted line) located just below the anterior commissure. In a moment, the needle will enter the papillomas at the "X".
Blanching (2 of 3)
The needle is buried and the tissue is blanching due to hydrostatic pressure of the injected fluid. The green dot is for reference with photo 3.
Obstructive papillomas (1 of 4)
This middle aged man has had lifelong RRP due to HPV 11. Primary focus of his recurrences for many years has been the trachea. Prior operative removals under general anesthesia have been challenging and recent work has used the thulium laser in an office setting. The papillomas seen here explain his mild pre-procedure stridor. His tracheal lumen should be approximately the size of the dotted circle.
Local injections (2 of 4)
A needle catheter passed through the channel of the scope is embedded at arrow, and is injecting 1% lidocaine with epinephrine (see blanched area). Numerous areas are similarly injected.
Removal of papilloma (3 of 4)
Here a large chunk of papilloma (stuck to the laser fiber at arrow) is being pulled away.