Recurrent Respiratory Papillomatosis (RRP) and Other HPV-Induced Lesions

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:

  1. Both the “carpet-variant” and wart-like growths are lesions that sometimes appear, either independently or together, in patients who have HPV;
  2. 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;
  3. Both the “carpet-variant” and wart-like growths can disrupt voice function;
  4. 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.


Photos:

Humility Before the HPV Virus—A Recurrence of Papillomas at Ten Years

HPV infection is considered chronic, and causes recurrent growth of papillomas in the larynx. Still, we sometimes see what appear to be cures, or at least long-term remissions. That appears to be the case here. After an 8 year interval of perfect voice, the patient had a sudden increase of hoarseness occurring in the few weeks prior to the last examination below. This is an illustration of why we often say to a patient who appears to be cured, “You may be cured, but we usually say “long term remission.”  This patient’s scenario is not rare. Was her longterm, 8-year remission due to meticulous surgery?  Cidofovir? Her immune response?  It is impossible to say if it was one or all of these factors.

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Stippled Vascularity (1 of 8)

In a somewhat distant view from 10 years earlier, under standard light, both vocal cords appear to be covered with stippled rather than (normal) linear or curvilinear vascularity. The diagnosis (biopsy confirmed): laryngeal papillomatosis aka RRP (recurrent respiratory papillomatosis), type 6.

HPV infection (2 of 8)

A somewhat closer view under blue-green narrow band light accentuates the stippled vascularity so typical of HPV infection. Both true cords are covered and there are patches on the false cords (arrows).

Stippled vascularity (3 of 8)

After surgery and cidofovir injection a year earlier, voice remains normal to the patient. Sharp eyes can pick up a tiny focus of stippled vascularity of the right cord (left of photo).

HPV vascular effect (4 of 8)

At closer range with narrow band light, the HPV vascular effect on the right cord is made more obvious (arrows). The patient requested a “curative mode” additional surgery to clear up this tiny residue and inject cidofovir.

16 months later (5 of 8)

16 months later, voice remains normal to patient, and there is no sign of recurrent HPV vascularity or lesion.

Is it long-term remission? (6 of 8)

A slightly blurry narrow band view, again showing no sign of stippling. Is she “cured?” Or in long-term remission?

Recurrent Papilloma (7 of 8)

After 8 years of normal voice, the patient re-presented due to hoarseness, saying that her voice had been “perfect” up until a few weeks earlier. She was not sick, but noticed increased “drainage” and voice change. The explanation is a recurrent papilloma.

Stippled vascularity (8 of 8)

Narrow band light again accentuates the stippled vascularity. The patient is embarking on another “curative mode” series of surgical procedures, hoping to again put her into remission.

Papillomas, HPV Subtype 11, before and After Removal

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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, removed: HPV Subtype 11 (4 of 4)

Closer view of left posterior vocal cord, narrow band illumination. Notice that there are a few dot-like vascular marks. These are typical of HPV effect, and may presage recurrence.

Papillomas, HPV Subtype 6, Before and after Removal

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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: HPV Subtype 6 (2 of 4)

Same lesion, under narrow band illumination.

Papillomas, removed: HPV Subtype 6 (3 of 4)

After removal and cidofovir injection, normalized larynx. Voice is normal.

Papillomas, removed: HPV Subtype 6 (4 of 4)

Same view, under narrow band illumination.

Papillomas, HPV Subtype 11

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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.

Papillomas: HPV Subtype 11 (3 of 3)

Still closer view, to see more clearly the anterior commissure papilloma.

HPV Lesions

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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 of HPV Subtype? (2 of 2)

Same patient, narrow band light. Now seen is the stippled, HPV-effect kind of vascularity of “carpet-variant” lesions.

Lesions and Papillomas of HPV, Before and After Removal and Adjuvant Injection

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Lesions and papillomas of HPV subtype? (1 of 8)

At initial diagnosis, as yet untyped for HPV. Multi-focal lesions on both vocal cords.

Subtle lesion (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).

Open phase (3 of 8)

Strobe light, open phase of vibration, showing mismatch.

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.

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.

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.

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.

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, Going Into Remission

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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, in remission: HPV Subtype 55 (4 of 4)

Same exam as photo 3, with narrow-band lighting. The vascular dots on the vocal cords are not HPV-related.

Papillomas, HPV Subtype 11

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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 11 (2 of 2)

Tracheal view, standard light, showing scattered papillomas (arrows). The carina is in the distance.

Papillomas, HPV Subtype 31, Going Into Remission

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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.

Papillomas, in remission: HPV Subtype 31 (4 of 4)

Closer view than photo 3, under narrow-band light.

Papillomas, HPV

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Papillomas: HPV Subtype? (1 of 2)

Papillomas involving both the true and false vocal cords.

Papillomas: HPV Subtype (2 of 2)

At higher magnification, the stippled vascular markings become more evident.

Pushing Past Red Herrings to Find the Real Issue

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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).

Carpet-varient papilloma (3 of 3)

At closer range, still under narrow band light, carpet-variant papilloma can be seen on the posterior right vocal cord (left of photo). This is the important finding.

Papillomas, HPV Subtype 18 or 45

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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.

Papillomas: HPV Subtype 18 or 45 (2 of 2)

Slightly magnified view of the same papilloma growths under narrow-band illumination, which accentuates the vascular pattern.

Lesions of HPV Subtype 16

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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.

Lesions of HPV Subtype 16 (3 of 3)

A similar view to image two, but with narrow-band illumination, which accentuates the vascular pattern. Biopsy/removal of these lesions revealed high-grade dysplasia; re-biopsy almost a year after this examination returned a diagnosis of cancer.

Cancer, HPV Subtype 16, Before and After Radiation

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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.

Cancer: HPV Subtype 16, after radiation therapy (5 of 5)

Strobe light, closed phase of vibration. The more normal right cord (left of image) unsuccessfully attempts to reach the left cord’s residual upper surface mucosa. Voice is functional but hoarse.

Papillomas, HPV Subtype 45

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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.

Papillomas: HPV Subtype 45 (2 of 2)

Closer view of the vocal cords, showing leukoplakia. This is presumably a second expression of the HPV infection, though the typical dotted or pointed vascular marks of HPV are not seen in the area of the leukoplakia.

Mid-Tracheal Papilloma, Treated By Thulium Laser

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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.

Months after treatment: no papilloma (5 of 5)

Durable resolution of papilloma, many months afterwards. Compare with photo 1.

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

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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.

Subtle papillomas, HPV subtype 6 (3 of 3)

With the vocal cords now at the pre-phonatory instant, these low-profile HPV-related papillomas are again seen, indicated by dotted lines.

HPV Vascular Effect

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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.

HPV vascular effect (3 of 3)

HPV vascular effect is seen even more clearly.

Laryngeal Papillomas Rarely Can be Found by … Accident

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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.

Narrow band light (2 of 4)

Narrow band light makes the papillomas much more evident.

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.

Open phase (4 of 4)

Open phase of vibration, strobe light. The plan is definitive removal and HPV subtyping.

Winning Papilloma Battles, but not Winning the War….Yet

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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…

HPV disease (8 of 8)

Still under narrow band light, stippled vascularity in the area of the arrows suggests that this elevated area also represents HPV disease.

What “Cured” this Case of RRP? Surgery? Cidofovir? The Patient’s Immune System? All Three?

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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.

3 years later, no sign of papilloma (8 of 8)

3 years later, there is still no sign of papilloma or stippled vascularity (HPV effect).

RRP Cure? Or Just Long Term Remission?

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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.

Narrow band lighting (4 of 4)

An even closer view under narrow band light still shows no sign of HPV effect or papilloma. Voice is normal and vibratory flexibility is maintained when examined under strobe light.

Polyps Need A Close Look: Here’s One Reason Why

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"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.

Prephonatory instant (4 of 4)

Prephonatory instant shows additionally that the right vocal cord lesion (left of photo) is in the wrong location for vibratory injury.

Long-term Remission or even “cure” of RRP/Laryngeal Papilloma

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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 (3 of 6)

Again under standard light but at higher magnification.

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.

Post-operation, narrow band lighting (6 of 6)

Under narrow band light, no stippled vascularity is seen. The question is: is remission due to surgery, cidofovir, or the patient's immune system?

Injected Local Anesthetic Causes Blanching

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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.

Subglottis being injected (3 of 3)

Farther below the vocal cords, the anterior subglottis is seen here being injected. The green dot is for reference with photo 2. The shank of the needle guide looks like a "Doctor Octopus" arm!

Local Rather than Topical Anesthesia can Permit Fairly Major Tracheal Surgery

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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.

Improved breathing with papilloma removal (4 of 4)

An additional chunk is being detached. The patient’s breathing at the conclusion of this procedure is much improved. The tracheal lumen will be even larger when a lot of remaining coagulated papillomas slough away.

Videos:

Papillomas of the Larynx and Trachea
This video shows wart-like growths in the voicebox and windpipe (larynx and trachea) caused by chronic infection with the human papillomavirus (HPV).
Pulsed-KTP Laser Coagulation of Vocal Cord Papillomas
See a video demonstration of laser coagulation of vocal cord papillomas.
Recurrent Respiratory Papillomatosis (RRP) | What Is It?
In this video, Dr. Robert Bastian discusses chronic human papilloma virus (HPV) infection of the larynx (especially vocal cords), causing hoarseness.

Chondroma

Chondroma is a benign growth composed of cartilage cells.


Chondroma of Thyroid Cartilage

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CT scan of the larynx (1 of 4)

CT scan of the larynx, showing the thyroid cartilage (outlined by gray dotted lines) and an abnormality deforming the thyroid cartilage on one side (between the white arrows). Note how the thyroid cartilage bulges on that side, as compared with the opposite side, and the black speck which indicates varying densities in the cartilage.

Endoscopic View of the Larynx (2 of 4)

Same patient, endoscopic view of the larynx, again showing the abnormality (at arrows). Here the abnormality looks similar to a saccular cyst, but the scan (and subsequent biopsy) shows that it is cartilaginous and a chondroma, not chondrosarcoma.

Chondroma of thyroid cartilage (3 of 4)

Closer view of the chondroma, showing an almost bi-lobed appearance.

Left Vocal Cord Sits Lower Then the Right (4 of 4)

Under strobe lighting, which shows that the left vocal cord (right of photo) is apparently at a lower level than the opposite cord.

Amyloidosis

A condition in which abnormal proteins (called amyloids) become deposited in the spaces between cells. In some cases, the cause of amyloidosis is a systemic disorder in which the body over-produces proteins–for example, multiple myeloma, a blood disease; in this scenario, the amyloid deposits can be dispersed widely across the body. In other cases, the amyloid deposits do not seem to reflect systemic disease and can be more organ-specific.

Amyloidosis in the larynx:

In laryngeal amyloidosis, the deposits seem to be localized either just to the larynx, or to the larynx and pharynx. One sees what looks like yellowish candle wax within the tissues. The amyloid deposits are quite firm, and when biopsied, there is little bleeding.

Treatment for laryngeal amyloidosis:

Because of their infiltrative nature, amyloid deposits typically cannot all be dissected out of the larynx; instead, then, an operating physician will aim to debulk the deposits in areas where they impair breathing or the voice. That is, when deposits are widespread in the larynx, there does not seem to be any point in removing them except in locations where removal will improve function. Often, repeated procedures are required over many years’ time, though occasionally the condition seems to stop progressing.


Photos:

Amyloidosis, before and after debulking: Series of 4 photos

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Amyloidosis, before debulking (1 of 4)

Panoramic view. Submucosal amyloid deposits in pharyngeal walls and epiglottis, with examples at arrows.

Amyloidosis, before debulking (2 of 4)

View of anterior subglottis shows diffuse infiltration of yellowish, submucosal amyloid.

Amyloidosis, before debulking (3 of 4)

Phonation under strobe light shows deposit at anterior commissure tethering upper surface of left vocal cord, and resultant vibratory asymmetry.

Amyloidosis, after debulking (4 of 4)

Some months later, after laser debulking at short arrow, showing improvement of vibratory closure after tethering reduced. Note increase of nearby supraglottic amyloid deposit does not need to be addressed because it has no functional consequence to the patient, who has other asymptomatic deposits in subglottis, epiglottis, and nasopharynx.

Amyloidosis of the Larynx as Seen Over Time, with Treatment

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Primary laryngeal amyloidosis (1 of 7)

An example of primary laryngeal amyloidosis of the larynx. In this case, the yellowish, “candle-wax” proteinaceous material is being deposited just below the margin of the vocal cords (arrows)

Bulky swelling (2 of 7)

When this person produces voice, the bulky swelling just below the margin of the vocal cords creates turbulence, incomplete match, and a rough voice quality. After laser debulking, the patient had a much improved voice for many years.

Amyloidosis (3 of 7)

Eight years later, the patient reappeared. She said voice had been good for many years but had been getting increasingly hoarse for the prior couple of years. Here you see major re-deposition of amyloid material.

Amyloid deposits (4 of 7)

At very close range, the yellowish color typical of amyloid deposits is better seen.

Vocal cords cannot close completely (5 of 7)

During voice production under strobe light, the amyloid deposit under the left vocal cord prevents closure.

Amyloids Remain (6 of 7)

A year after laser debulking, the patient continued to have a very good voice, and only reappeared due to an unrelated question. As expected, smally amyloid deposits remain.

Voice remains clear (7 of 7)

When she produces voice, match and vibratory ability are very good, explaining her normal voice. It remans to be seen if amyloid will gradually reaccumulate over the next many years and need another debulking.

Amyloidosis: Series of 1 photo

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Amyloidosis (1 of 1)

Amyloid deposits (arrows) at the carina, where trachea splits into right and left mainstem bronchi, as well as a few centimeters down the left mainstem bronchus (smaller arrow). The deposits appear yellowish and widen or project from the tissues they infiltrate.

Amyloidosis, before and after debulking: Series of 8 photos

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Amyloidosis, before debulking (1 of 8)

Panoramic view of a large spherical mass of amyloid material bulging submucosally (contour at dotted line) in the false and aryepiglottic cords. The patient has only a harsh stage whisper, and glottic voice only with inspiratory (inhaling) phonation. The posterior vocal cord and ventricle of the opposite side (left of photo) are visible, but the amyloid mass obscures all but a few millimeters of the posterior cord on its side.

Amyloidosis, before debulking (3 of 8)

View yet further down, showing the upper trachea (top-center of photo), the posterior end of one of the vocal cords (left of photo), and the edge of the amyloid mass (bottom-right of photo, again marked by a dotted line). The mass is again obscuring a view of the vocal cord on its side; in fact, it is pressing the cord downward, which affects the voice.

Amyloidosis, before debulking (4 of 8)

Phonation, while attempting to see the vocal cords beyond the large overhanging mass. The vocal cords are each marked with an F, one of the posterior ventricles with a V, and the amyloid mass with an A. This mass actually overlies most of both vocal cords and presses them both downward.

Amyloidosis, after debulking (5 of 8)

Twenty-four hours after laser removal, i.e., debulking.

Amyloidosis, after debulking (6 of 8)

Looking into the deepest recess of the dissection. The parallel lines indicate the upper border of the thyroid cartilage.

Amyloidosis, after debulking (7 of 8)

After debulking, both vocal cords are now visible from this angle (compare with photo 2). Remaining swollen overhanging tissue did not appear to be infiltrated with amyloid deposition.

Complete healing (8 of 8)

Many months after debulking, and with complete healing, the voice can pass for normal, and the laryngeal vestibule is no longer filled with the enormous bulk of amyloid. The nubbin at anterior false cord would only need removal if it became large enough to interfere with voice.

Proteinaceous deposits of primary laryngeal amyloidosis can occur anywhere and “everywhere” in the larynx: Series of 4 photos

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Airway Passage (1 of 4)

This middle-aged woman has experienced gradual deterioration of voice across several years. Note the narrowed airway and protruding lesions.

Submucosal Masses (2 of 4)

In a closer view, one gets the sense of firm submucosal masses (most prominent deposits circled, at arrows). Note the yellowish cast as well. Vocal cord margins are marked with dotted lines.

Amyloid Deposits (3 of 4)

At closer range, the yellowish cast typical of amyloid deposits is seen better.

Diffuse Subglottic Infiltration (4 of 4)

Just below the vocal cords, diffuse subglottic infiltration is also seen, with the most prominent deposit posteriorly at the arrow.

Videos:

Amyloidosis
This video gives an example of amyloidosis, which is a condition in which abnormal proteins (called amyloids) become deposited in the spaces between cells.

Verrucous Carcinoma

Verrucous carcinoma is a variant of squamous cell carcinoma (SCCA). In the head and neck, this uncommon subtype of SCCA is seen most often in the oral cavity or on the vocal cords. Visually, it tends to have an exophytic (outward-growing) and wartlike, irregular surface. This variant of SCCA is typically less aggressive than other squamous cell carcinomas. Local recurrence tends to be the issue more than distant metastasis. Surgery tends to be the most effective treatment, though of course every patient’s circumstance is individualized and considered in the light of three treatment options: surgery, radiation therapy, and chemotherapy.


Photos:

Verrucous Carcinoma, Before and After Laser Treatment

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Verrucous carcinoma (1 of 5)

Verrucous carcinoma, left vocal cord, persistent after radiotherapy elsewhere, in a patient unable to undergo general anesthesia due to severe lung disease.

Verrucous carcinoma, after laser treatment (3 of 5)

After several Thulium Laser ablations, using topical and injected local anesthesia, with patient sitting in examination chair, thereby avoiding general anesthesia.

Verrucous carcinoma, several weeks after laser treatment (4 of 5)

Approximately six weeks later, durable resolution of tumor. Yellow material is mucus.

Verrucous carcinoma, several weeks after laser treatment (5 of 5)

During voicing. Arytenoid moves, but much of membranous vocal cord has been ablated as intended.

Sarcoma

A sarcoma is a malignant tumor that originates in mesenchymal tissue. Mesenchymal tissue comprises muscle, bone, fat, connective tissue, blood vessels, and cartilage. If, instead, a malignancy originates in lining or covering tissues—which includes skin, bronchial tubes, the lining of the mouth, throat, and gastrointestinal tract, and breast and salivary gland ducts—then that tumor is called a carcinoma.

Carcinomas are far more common than sarcomas, and sarcomas involving the larynx are rare, with chondrosarcoma (“chondro-” refers to cartilage origin) heading the list. The clinicians at our laryngology practice have seen hundreds of carcinomas in their career, but probably no more than 20 sarcomas.


Photos of Sarcoma

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Sarcoma (1 of 2)

Sarcoma of larynx. The tumor nearly fills the glottis.

Sarcoma (2 of 2)

Closer view, showing the posterior commissure airway.

Human Papillomavirus (HPV) Infection of the Larynx

A DNA virus that may cause cutaneous warts, genital warts, or the clinical condition recurrent respiratory papillomatosis (RRP) in susceptible individuals. Human papillomavirus (HPV) may occur in as many as 150 or more subtypes. The most common subtypes seen in patients with RRP are HPV 6 and 11. Other less common subtypes that can induce papillomas or other growths within the larynx include HPV 16, 18, 31, 44, 45, 55, 69, 84 & 11, 33 & 45 and some of these subtypes are associated with a higher risk of cancer formation. See the photo series below, displaying all of the subtypes mentioned above. For a paper describing HPV subtypes in the larynx, see also this Bastian Voice Institute article.

Common Questions About HPV

Q:  What is the relationship between the terms RRP, HPV, and Papilloma?

A:  The underlying disorder is HPV (human papilloma virus) infection of the airway, especially the larynx.  The virus “sets up house” chronically inside airway and stimulates a kind of proliferation called papillomas, or papillomatosis. Because these lesions tend to recur after surgical removal, the clinical syndrome has become referred to as recurrent respiratory papillomatosis (RRP).

Q:  HPV apparently has different subtypes.  What can you tell me about them?

A:  Human papilloma virus infection can consist of as many as 150 different subtypes.  Some are related to skin infection (causing warts).  Some are more common in genital or respiratory sites. Genital lesions are typically called condylomata, or genital warts.  In the airway, the lesions are typically called papillomas. Commonest subtypes in the airway are types 6 and 11. These two subtypes comprise the vast majority of our patients at Bastian Voice Institute (BVI). We have patients who have also tested positive for types 16, 18, 45, 55, and a few others.

Q:  I have a low-risk subtype of HPV.  Can you explain what this means?

A: The human papilloma virus (HPV) comes in 150 or more subtypes. Think of it like the many models of automobiles that all fall under the designation “Ford.”  Subtypes found most often in the respiratory and genital tracts are 6 and 11. HPV infection is associated with some degree of risk of stimulating, or converting to, a carcinoma.  Hence the higher risk of cervical cancer in women with HPV infection.  Some subtypes are considered to have a low risk of viral carcinogenesis; others have a high risk. At BVI, the majority of our many adult patients have 6 or 11, both of which are low-risk subtypes.  We also have one or two who have both 6 and 11.  Then we have a handful of patients with intermediate or high risk for cancer.  A few of these high-risk subtypes have in fact caused cancers in our population of ~150 adult patients with RRP. Thankfully, all have responded well to treatment and none to my memory have died from their cancer.


Photos:

Subtype 6

More common subtype seen in the airway. HPV 6 is associated with a lesser risk of cancer formation, as is HPV 11.

Humility Before the HPV Virus—A Recurrence of Papillomas at Ten Years

HPV infection is considered chronic, and causes recurrent growth of papillomas in the larynx. Still, we sometimes see what appear to be cures, or at least long-term remissions. That appears to be the case here. After an 8 year interval of perfect voice, the patient had a sudden increase of hoarseness occurring in the few weeks prior to the last examination below. This is an illustration of why we often say to a patient who appears to be cured, “You may be cured, but we usually say “long term remission.”  This patient’s scenario is not rare. Was her longterm, 8-year remission due to meticulous surgery?  Cidofovir? Her immune response?  It is impossible to say if it was one or all of these factors.

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Stippled Vascularity (1 of 8)

In a somewhat distant view from 10 years earlier, under standard light, both vocal cords appear to be covered with stippled rather than (normal) linear or curvilinear vascularity. The diagnosis (biopsy confirmed): laryngeal papillomatosis aka RRP (recurrent respiratory papillomatosis), type 6.

HPV infection (2 of 8)

A somewhat closer view under blue-green narrow band light accentuates the stippled vascularity so typical of HPV infection. Both true cords are covered and there are patches on the false cords (arrows).

Stippled vascularity (3 of 8)

After surgery and cidofovir injection a year earlier, voice remains normal to the patient. Sharp eyes can pick up a tiny focus of stippled vascularity of the right cord (left of photo).

HPV vascular effect (4 of 8)

At closer range with narrow band light, the HPV vascular effect on the right cord is made more obvious (arrows). The patient requested a “curative mode” additional surgery to clear up this tiny residue and inject cidofovir.

16 months later (5 of 8)

16 months later, voice remains normal to patient, and there is no sign of recurrent HPV vascularity or lesion.

Is it long-term remission? (6 of 8)

A slightly blurry narrow band view, again showing no sign of stippling. Is she “cured?” Or in long-term remission?

Recurrent Papilloma (7 of 8)

After 8 years of normal voice, the patient re-presented due to hoarseness, saying that her voice had been “perfect” up until a few weeks earlier. She was not sick, but noticed increased “drainage” and voice change. The explanation is a recurrent papilloma.

Stippled vascularity (8 of 8)

Narrow band light again accentuates the stippled vascularity. The patient is embarking on another “curative mode” series of surgical procedures, hoping to again put her into remission.

Papillomas, HPV subtype 6, before and after removal

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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: HPV Subtype 6 (2 of 4)

Same lesion, under narrow band illumination.

Papillomas, removed: HPV Subtype 6 (3 of 4)

After removal and cidofovir injection, normalized larynx. Voice is normal.

Papillomas, removed: HPV Subtype 6 (4 of 4)

Same view, under narrow band illumination.

Subtle papillomas, HPV subtype 6

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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.

Subtle papillomas, HPV subtype 6 (3 of 3)

With the vocal cords now at the pre-phonatory instant, these low-profile HPV-related papillomas are again seen, indicated by dotted lines.

Subtle papillomas and the importance of a motivated examination

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Standard light, HPV-6 infection (1 of 4)

Breathing position, standard light in a young woman with longstanding HPV-6 infection. Voice remains quite good, many months after her last microsurgery with cidofovir injection. The only obvious “lesion” is posterior right cord (left of image) but the characteristic punctate vascular marks are not seen. The black lines are purely for use to orient photo 4.

Stobe light, vocal cord margin irregularity (2 of 4)

With such a clear voice, this prephonatory instant under strobe light reveals a surprising degree of vocal cord margin “serpentine” irregularity. Black lines again support orientation with photo 4.

Narrow band light, vascular marks seen (3 of 4)

At very close range and also using narrow band light, the tiny punctate vascular marks are seen in the lesion first seen in photo 1. Faint vascularity like that demonstrated here can be a correlate of relatively stable, inactive disease, which has clinically been the case here.

Narrow band light, papilloma formation (4 of 4)

This narrow band view includes only the anterior half of the vocal cords from the black lines of photos 1 and 2 to the anterior commissure (at x). Inside the faint circles, note the vascular markings that suggest papilloma formation to explain the serpentine margin.

HPV Vascular Effect

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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.

HPV vascular effect (3 of 3)

HPV vascular effect is seen even more clearly.

Type 6 HPV Papillomas Firmer Than Most

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Stippled vascularity not seen (1 of 4)

Diffuse involvement of true and false cords with papilloma caused by HPV 6. After hundreds of procedures from childhood through early adulthood, the stippled vascularity is not extremely evident in this standard-light view.

HPV vascular effect (2 of 4)

At closer range, still under standard light, the characteristic vascularity—what we term “HPV vascular effect”—is only beginning to be evident (arrows).

Vascularity clearly seen (3 of 4)

At still closer range, and now under narrow-band light, stippled vascularity is clearly seen (arrows).

Under narrow-band light (4 of 4)

Even closer view still under narrow-band light: the stippled vascularity is now unmistakable.

HPV 6: Going, Going, Gone?

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“Curative mode” plan (1 of 7)

Known HPV 6-induced laryngeal papillomas, with resulting gross hoarseness. The plan is “curative mode” defined as 3 or more successive, surgical cleanouts with adjuvant injection to see if the disease can be put into remission or at the least “tamed” to less rapid recurrence.

Closer view (2 of 7)

At closer range. Still, the full extent of disease becomes more obvious at the anterior right vocal cord (left of photo at arrow) in the next photo, when viewed under narrow band illumination (NBI).

Narrow-band illumination (3 of 7)

Now under NBI, the right anterior vocal cord (left of photo) involvement is seen clearly.

Post surgery (4 of 7)

A few days after surgical removal using the usual “basement membrane peel” technique of removal and in this case cidofovir injection. Voice is already dramatically improved, the right cord (left of photo) retains vibratory ability, and the grey wound base is seen clearly.

Towards “management mode” (5 of 6)

Voice had been “normal” until recent weeks, and so the patient therefore waited longer than intended for followup surgery, to the point that we are drifting out of “curative mode” and over into “management mode.” Here, under standard light, the disease is not that obvious.

Same view under NBI (6 of 7)

Under NBI at closer range, the carpet of HPV upper surface and one actual papilloma are more evident, but it is still not quite clear why the patient says voice has been getting slightly hoarse.

Stippled vascularity seen (7 of 7)

At closer range, faint HPV-induced vascular stippling is seen along the margin of the right vocal cord (left of photo) within the dotted line, and this explains his subtle and increasing hoarseness. Another surgical cleanout with adjuvant medication is scheduled.

Subtype 11

One of the more common subtypes seen in the airway. HPV 11 is associated with a lesser risk of cancer formation, as well as HPV 6.

Papillomas, HPV Subtype 11, Before and After Removal

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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, removed: HPV Subtype 11 (4 of 4)

Closer view of left posterior vocal cord, narrow band illumination. Notice that there are a few dot-like vascular marks. These are typical of HPV effect, and may presage recurrence.

Papillomas, HPV subtype 11

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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.

Papillomas: HPV Subtype 11 (3 of 3)

Still closer view, to see more clearly the anterior commissure papilloma.

Papillomas, HPV subtype 11

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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 11 (2 of 2)

Tracheal view, standard light, showing scattered papillomas (arrows). The carina is in the distance.

Subtype 16

Less common in the airway than the more common subtypes 6 and 11. HPV 16 is associated with a higher risk of cancer formation, along with HPV subtypes 18, 31, 45, 55, and others.

Lesions of HPV Subtype 16

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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.

Lesions of HPV Subtype 16 (3 of 3)

A similar view to image two, but with narrow-band illumination, which accentuates the vascular pattern. Biopsy/removal of these lesions revealed high-grade dysplasia; re-biopsy almost a year after this examination returned a diagnosis of cancer.

Cancer, HPV Subtype 16, Before and After Radiation

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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.

Cancer: HPV Subtype 16, after radiation therapy (5 of 5)

Strobe light, closed phase of vibration. The more normal right cord (left of image) unsuccessfully attempts to reach the left cord’s residual upper surface mucosa. Voice is functional but hoarse.

Subtype 18

This is less common in the airway than the more common subtypes 6 and 11. HPV 18 is associated with a higher risk of cancer formation, along with HPV subtypes 16, 31, 45, 55, and others.

HPV 18—High Risk Subtype

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Papillomas seen (1 of 4)

Middle-aged man with chronic hoarseness and the lesions seen here, diagnosed by the pathologist as papillomas.

Stippled vascularity (2 of 4)

Closer view. Stippled vascular markings consistent with HPV effect are seen more clearly here.

Surgical removal (3 of 4)

Soon after microlaryngoscopic removal, and in preparation for followup cidofovir injection.

Cidofovir injection (4 of 4)

Needle (arrow) and blanching and swelling of the left cord as cidofovir is injected. The same technique can be used for Avastin.

Subtype 31

This is less common in the airway than the more common subtypes 6 and 11. HPV 31 is associated with a higher risk of cancer formation, along with HPV subtypes 16, 18, 45, 55, and others.

Papillomas, HPV Subtype 31, Going Into Remission

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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.

Papillomas, in remission: HPV Subtype 31 (4 of 4)

Closer view than photo 3, under narrow-band light.

HPV 31 As A Cause of “Chronic Laryngitis” 

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Hazy leukoplakia, HPV suspected (1 of 4)

This 20-something nonsmoker without reflux symptoms is chronically hoarse. HPV infection is suspected for the following reason: While hazy leukoplakia can be occasionally seen as a result of excessive voice use, it would be most unusual to this degree, and this far lateral to the vocal cord margin. Biopsy shows only chronic inflammation, and HPV testing is positive for subtype 31.

Leukoplakia remains (2 of 4)

Several months later, the inflammatory reaction with leukoplakia remains.

Leukoplakia demarcated (3 of 4)

Narrow band illumination here makes the leukoplakia patches more demarcated.

HPV effect confirmed (4 of 4)

Within the circle, one can see faint HPV-effect on vasculature (stippling).

HPV 31 → Cancer → Cure

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Carcinoma in situ (1 of 4)

This man developed hoarseness spontaneously a year before this visit. He had accumulated 30 pack-years as a smoker, but had quit 7 years earlier. Removal of “polyps” elsewhere returned a diagnosis of carcinoma in situ (CIS), the earliest stage in the development of cancer.

HPV subtype 31 (2 of 4)

Under narrow band light, note some unusual “suspicious” capillaries, and the stippled “HPV effect” at the arrow. These findings triggered HPV subtyping and identification of high-risk subtype 31.

Excisions (3 of 4)

After 2 prior excisions elsewhere with positive margins, somewhat aggressive excision was performed in the operating room, attempting to avoid the need for radiotherapy in this fairly young man. The specimen showed severe dysplasia/ CIS, but with negative margins. After some months, voice became very functional.

Seven years later (4 of 4)

Seven years later, at an annual visit, there are no stippled or other abnormal vascular marks. Voice has been very acceptable to the patient, if occasionally faintly husky.

Subtype 44

HPV 44

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Voiceless 50-year-old man (1 of 6)

This 50-year-old man is virtually aphonic. The vocal cord abnormality is already visible in this distant view.

Vascular stippling (2 of 6)

At closer range and under standard light, the vascular stippling is becoming more visible. The two small 'X's are for reference with Photo 3.

Narrow band light, vascularity (3 of 6)

At even closer range under narrow band light, the vascularity is even more evident. The two small 'X's are for reference with Photo 2.

4 months later, recurrent papillomas (4 of 6)

This man had marked improvement of voice after surgery 4 months earlier but within weeks, voice began to deteriorate due to regrowth of his papillomas.

Open position, narrow band light (5 of 6)

Still in open (breathing) position but now under narrow band light. The stippled vascular markings typical of HPV effect are seen more clearly.

Closing for voicing (6 of 6)

As the cords come into approximation for voicing, still under narrow band light, the recurrent lesions are again seen.

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Stippled vascularity (1 of 4)

An older man with chronic hoarseness is found to have these lesions. Stippled vascular markings are typical of papillomas, caused in this case by HPV 44.

Narrow-band lighting (2 of 4)

Under narrow band light, the vascular markings are more evident.

4 months later (3 of 4)

Early after removal of the papillomas, voice is dramatically improved and the cords are nearly healed.

Closer view (4 of 4)

Closer view, showing only residual hazy white areas of incomplete healing of the early postsurgical “wounds.”

Subtype 45

This subtype is less common in the airway than the more common subtypes 6 and 11. HPV 45 is associated with a higher risk of cancer formation, along with HPV subtypes 16, 18, 31, 55, and others.

Papillomas, HPV Subtype 45

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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.

Papillomas: HPV Subtype 45 (2 of 2)

Closer view of the vocal cords, showing leukoplakia. This is presumably a second expression of the HPV infection, though the typical dotted or pointed vascular marks of HPV are not seen in the area of the leukoplakia.
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HPV type 45 detected (1 of 7)

Panoramic view shows marked enlargement from tumor of false cords. Biopsy shows squamous cell and cancer HPV type 45 is also detected as the likely cause.

Closer view of HPV effect (2 of 7)

Closer view of the true vocal cords showing HPV effect of vascular stippling.

Narrow band illunination (3 of 7)

Narrow band illumination accentuates HPV vascular effect.

Post radiotherapy, glottic web seen (4 of 7)

After radiotherapy with complete response. A glottic web is now seen as a radiation side effect/complication.

Post-radiation web (5 of 7)

Closer view of post-radiation web.

Post-microlaryngoscopy, release of glottic web (6 of 7)

After microlaryngoscopy and release of glottic web. Tumor is gone.

HPV effect no longer seen (7 of 7)

Closer view of final result; patient has very good voice. Note that the HPV-related stippled vascularity is no longer seen.

Subtypes 33 & 45

HPV and Cancer: Types 33 and 45

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Hoarse voice (1 of 5)

Chronic hoarseness in a younger woman, diagnosed elsewhere with “nodules.”

Narrow band light (2 of 5)

At closer range, under narrow band light. Note the two distinct vascular patterns: a finer, stippled one of anterior 1/3 and a more coarse and aberrant one on the mid and posterior fold. The pathology report shows invasive carcinoma-in-situ, which was removed using the CO2 laser.

Post excision (3 of 5)

One week after excision of the lesion.

Healed (4 of 5)

After healing, the right fold normalizes remarkably and the patient’s voice sounds normal to her and to the clinician.

"Cured" (5 of 5)

Two years later, laser excision alone (no doubt along with the patient’s immune system) has produced a durable remission/ “cure.”

Subtype 55

This subtype is less common in the airway than the more common subtypes 6 and 11. HPV 55 is associated with an intermediate degree of risk of cancer formation, as compared to other subtypes of HPV.

Papillomas, HPV Subtype 55, Going Into Remission

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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, in remission: HPV Subtype 55 (4 of 4)

Same exam as photo 3, with narrow-band lighting. The vascular dots on the vocal cords are not HPV-related.

Subtype 69

HPV Subtype 69 (High-Intermediate Risk)

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Standard lighting (1 of 2)

Here, right vocal cord (left of photo) is unaffected, while left cord is entirely covered with papillomas caused by HPV 69.

Narrow band lighting (2 of 2)

At close range, under narrow band light, the vascular pattern is more strikingly revealed.

HPV 84 & 11

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Chronic hoarseness, papilloma (1 of 5)

60-something man with chronic hoarseness due to these lesions, seen under standard light. Biopsy shows "papilloma" and HPV testing reveals subtypes 84 & 11.

Stippled vascularity, leukoplakia (2 of 5)

At closer range under narrow band light, the stippled "HPV effect" vascularity is seen more clearly. The lesion marked by 'X' in this photo and photo 1 shows a subtle degree of leukoplakia.

Post treatment, voice is very good (3 of 5)

After several micro laryngoscopes, first using cidofovir as an adjuvant, and then avastin, the larynx looks quite clear. Voice is also very good.

Closed phase (4 of 5)

Under strobe light, closed phase of vibration.

Open phase (5 of 5)

Open phase of vibration.

Carcinoma In Situ (CIS)

Carcinoma in situ (CIS) is a lesion comprised of “cancer cells,” but with those cells limited to the lining mucosa and without evidence of extension to adjacent structures. In other words, there is no sign of invasion beyond the mucosa. CIS is typically a localized and highly curable precursor to invasive cancer. It is sometimes called intraepithelial carcinoma.

In laryngology, CIS is found primarily on the vocal cords themselves, where a tiny, early lesion can change the quality of the voice. In other locations, CIS would ordinarily be “silent.”


Radiation: Telangiectasia Increases Slowly but is Maximal by 3 Years after End of Radiation

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Inflammation with moderate dysplasia (1 of 8)

Hoarseness began 2 years prior to this initial examination photo. This middle aged man has never smoked; has no reflux symptoms, nor has he had any response to empiric reflux therapy. Biopsy shows inflammation with moderate dysplasia. HPV testing was negative. No explanation for this chronic inflammation is ever found. A series of KTP laser treatments of stippled vascular areas and leukoplakia ensues.

Squamous cell carcinoma-in situ (2 of 8)

A year later, similar findings except appearance of a slight anterior commissure inflammatory web. Eventually, after an additional 2 years (5 years after onset of hoarseness) a second biopsy is triggered by aberrant, “corkscrew” capillaries. The diagnosis: squamous cell carcinoma-in situ. Laser excision is typically preferred for well-demarcated early vocal cord cancer, but the diffuse, superficial and bilateral abnormalities suggested radiotherapy instead.

Post radiation (3 of 8)

Six weeks after the end of his 30 radiation treatments, healing of the superficial ulceration (within dotted lines) is underway.

Narrow band light (4 of 8)

Closer view, now under narrow band light: A fine vascular pattern has returned except in the areas bounded by dotted lines.

Regenerated vascular pattern (5 of 8)

Six weeks later (3 months after end of radiotherapy), the superficial ulceration has healed, and voice is very functional. Note the regenerated vascular pattern, and compare with photo 4.

Post-radiation telangiectasias (6 of 8)

“On schedule” a year after the end of successful radiation therapy, post-radiation telangiectasias are becoming evident. Compare progression of these telangiectasias in photos 4, 5, 6, 7, and 8.

Standard light (7 of 8)

Now 3 years from the end of radiotherapy, radiation telangiectasia are “maximal” and stable. Voice remains very good.

Narrow band light (8 of 8)

Same view, under narrow band light.

HPV and Cancer: Types 33 and 45

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Hoarse voice (1 of 5)

Chronic hoarseness in a younger woman, diagnosed elsewhere with “nodules.”

Narrow band light (2 of 5)

At closer range, under narrow band light. Note the two distinct vascular patterns: a finer, stippled one of anterior 1/3 and a more coarse and aberrant one on the mid and posterior fold. The pathology report shows invasive carcinoma-in-situ, which was removed using the CO2 laser.

Post excision (3 of 5)

One week after excision of the lesion.

Healed (4 of 5)

After healing, the right fold normalizes remarkably and the patient’s voice sounds normal to her and to the clinician.

"Cured" (5 of 5)

Two years later, laser excision alone (no doubt along with the patient’s immune system) has produced a durable remission/ “cure.”

HPV 31 → Cancer → Cure

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Carcinoma in situ (1 of 4)

This man developed hoarseness spontaneously a year before this visit. He had accumulated 30 pack-years as a smoker, but had quit 7 years earlier. Removal of “polyps” elsewhere returned a diagnosis of carcinoma in situ (CIS), the earliest stage in the development of cancer.

HPV subtype 31 (2 of 4)

Under narrow band light, note some unusual “suspicious” capillaries, and the stippled “HPV effect” at the arrow. These findings triggered HPV subtyping and identification of high-risk subtype 31.

Excisions (3 of 4)

After 2 prior excisions elsewhere with positive margins, somewhat aggressive excision was performed in the operating room, attempting to avoid the need for radiotherapy in this fairly young man. The specimen showed severe dysplasia/ CIS, but with negative margins. After some months, voice became very functional.

Seven years later (4 of 4)

Seven years later, at an annual visit, there are no stippled or other abnormal vascular marks. Voice has been very acceptable to the patient, if occasionally faintly husky.

Carcinoma

Carcinoma is a malignancy originating in the tissues that line the surfaces and cavities of the body.

See also: cancer, carcinoma in situ, and verrucous carcinoma.


Radiation Mucositis

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Prior to start of radiation (1 of 4)

Patient with vocal cord carcinoma, primarily of the right true cord (left of picture). This is before radiation therapy began, so there is not yet any radiation mucositis.

Radiation mucositis, 1 week after radiation (2 of 4)

One week after the end of radiation therapy. The tumor has disappeared. Radiation mucositis is evident from the patches of grey (arrows), which are superficial ulceration.

Radiation mucositis, 4 weeks after radiation (3 of 4)

Almost four weeks after the end of radiation therapy. Note that the mucositis has begun resolving, especially on the right cord (left of picture).

Disappearing radiation mucositis, 10 weeks after radiation (4 of 4)

Almost ten weeks after the end of radiation therapy. The mucositis is virtually gone.

Laser Surgery for Bilateral Vocal Cord Cancer

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Squamous cell carcinoma (1 of 6)

This man developed hoarseness across a few months. Biopsy elsewhere revealed squamous cell carcinoma, seen here on both vocal cords. Based upon a friend’s experience, he rejected radiotherapy, opting for laser resection, knowing it could be very hard on voice.

Tumor on the vocal cords (2 of 6)

At closer range and under narrow band (blue-green) light to accentuate the vascular abnormalities associated with this tumor.

Granuloma delays voice recovery (3 of 6)

Six weeks after superficial laser cordectomy, the larynx is almost healed with the exception of a small granuloma, left vocal cord (right of photo). When healing includes granulation, voice recovery is delayed as the granuloma resolves.

Closer view of granuloma (4 of 6)

He has hoarse but functional voice, but under strobe light, the granuloma prevents vibratory closure. Note the medial-to-lateral capillary reorientation so typical after laser cordectomy.

Granuloma is smaller (5 of 6)

Now 3 ½ months from surgery, voice has improved further and he considers it “75%” of original...One can see that the granuloma is smaller.

Granuloma doesn't impede voice (6 of 6)

Note that the granuloma no longer prevents vibratory closure and this explains further improvement of voice. Compare with photo 4.

Tumor in Trachea

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Biopsy (1 of 4)

Tumor growing through wall of trachea, from a paratracheal lymph node. Biopsy forceps are about to close to take a tissue fragment for study.

After biopsy (2 of 4)

After biopsy was taken at arrow. The result: squamous cell carcinoma thought to be an unusual metastasis from unusually aggressive larynx cancer.

Tumor gone (3 of 4)

Soon after radiation therapy, the tumor has melted away, leaving a depression in the tracheal wall.

Slow return (4 of 4)

Eighteen months later, the patient has experienced a fairly durable response, with very slow return of tumor.

Vocal Cord Cancer

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Vocal cord cancer (1 of 1)

Carcinoma right vocal cord with a large lobule projecting upwards and medial to the false cord, too.

Vocal Cord Cancer, before, during, and after Radiation

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Vocal cord cancer (1 of 8)

Superficial cancer involving both vocal cords. This is stage 1 disease (T1B). The greatest bulk is on the right posterior cord (left of image), but the majority of both cords is involved with at least superficial disease. A faint dotted rectangle indicates the zoomed-in area seen in photo 2.

Vocal cord cancer (2 of 8)

Close-up view of only the anterior half of the cords. Notice the irregular surface, and areas of leukoplakia within this squamous cell carcinoma.

Vocal cord cancer, during radiation (3 of 8)

Just over midway through radiation treatment. One can see that the tumor is melting away.

Vocal cord cancer, during radiation (4 of 8)

Postcricoid / hypopharyngeal mucositis. In this view, the patient is performing a so-called trumpet maneuver to splay open the lower throat. The radiation delivered to the vocal cords (which inhabit the airway but are hidden here due to the momentary constriction of the laryngeal vestibule, at arrows) also causes superficial ulceration of the swallowing passage (upper half of the photo), directly behind the vocal cords. On occasion, if tissue reaction and mucositis are much more severe than seen here, a stricture can form, requiring dilation.

Vocal cord cancer, 2 months after radiation (5 of 8)

Two months after radiation is complete, showing that the tumor is gone, and the mucositis has resolved. There is a small anterior commissure web (at arrow) just below the free margin of the cords. The patient’s voice can nevertheless pass for normal.

Vocal cord cancer, 4 months after radiation (6 of 8)

Now four months after the end of radiation. Close-up view of the postcricoid / hypopharynx regions (compare with photo 4 in this series). Mucositis here is resolved as well, and there is no stricture.

Vocal cord cancer, 6 months after radiation (7 of 8)

Now six months after the end of radiation. Strobe illumination, open phase of vibration. Note that the contours of the vocal cords are not perfectly normal, even though voice is very good.

Vocal cord cancer, 6 months after radiation (8 of 8)

Strobe illumination, nearly closed phase of vibration. Oscillatory flexibility is preserved, but the vocal cord margins are not perfectly straight.

Hypopharyngeal Cancer, before and after Surgery

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Hypopharyngeal cancer (1 of 10)

Years after successful radiotherapy for glottic cancer, during a routine, yearly follow-up examination, a new hypopharyngeal cancer (invasive squamous cell carcinoma) is barely seen, at arrow. (For reference, X marks the same location in the larynx throughout this series.)

Hypopharyngeal cancer (2 of 10)

Trumpet maneuver begins, to splay open the post-arytenoid part of the posterior pharyngeal wall (arrows and dotted lines), as well as the pyriform sinuses on each side. The tumor is now seen clearly. (Note the change of perspective from photo 1, using X as a reference point.)

Hypopharyngeal cancer (3 of 10)

Similar view to photo 2 (still with the trumpet maneuver), but now with the tumor outlined.

Hypopharyngeal cancer (4 of 10)

Closer view than photos 2 and 3 (again, still with the trumpet maneuver), with the tumor still outlined. Radiation is not an option for this tumor because of prior larynx irradiation; an attempt at laser surgery was selected.

Hypopharyngeal cancer: 1 week after surgery (5 of 10)

One week after laser excision of the tumor. Note the widespread redness, and the swollen arytenoid mounds, especially on the right side of the image. Compare with photo 1.

Hypopharyngeal cancer: 1 week after surgery (6 of 10)

Panoramic view, with the patient beginning the trumpet maneuver. The surgical wound is coming into view. Compare with photo 2 (again, using X as a reference point).

Hypopharyngeal cancer: 1 week after surgery (7 of 10)

Maximum trumpet maneuver. Closer view of the surgical wound. Compare with photo 4.

Hypopharyngeal cancer: 1 week after surgery (8 of 10)

View into the left pyriform sinus, where the tumor was most bulky.

Hypopharyngeal cancer: several months after surgery (9 of 10)

Months after laser resection, panoramic view, showing the swallowing “crescent” (within dotted lines), at the upper limit of where the laser resection occurred. There is surgical stenosis at the entrance to the esophagus (shown in the next photo). This stenosis affects swallowing of solid food, but the patient says this is no problem for him, if he eats a little more slowly and chews well.

Hypopharyngeal cancer: several months after surgery (10 of 10)

With the trumpet maneuver, again splaying open the hypopharynx, as in photo 2. Notice the hypopharyngeal/ postcricoid stenosis; the dotted lines represent what would be a normal-sized opening.

Supraglottic Cancer

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Supraglottic cancer (1 of 4)

Middle-aged woman with sore throat, discovered to have a circumscribed exophytic squamous cell carcinoma at the petiole and anterior false cords.

Supraglottic cancer (2 of 4)

Closer view, showing the aberrant tumor vessels especially in the inferior half of the tumor, with less “white-out” from light overexposure.

Supraglottic cancer (3 of 4)

As is often the case, this tumor “respects” the ventricle, meaning it does not cross the plane of the ventricle (entrance at dotted line) to invade the true cords. An instrument could lift the inferior border of the tumor to show that the true cords aren’t invaded; the tumor is simply overlapping them.

Supraglottic cancer (4 of 4)

Under narrow-band lighting, the tumor’s aberrant vessels and its relationship to both the true and false cords are clearer. This is a supraglottic (not transglottic) tumor, likely amenable to outpatient endoscopic laser resection, and management of lymphatic compartments of the neck, depending on individual circumstances, via observation, radiotherapy, or selective neck dissection.

Vocal Cord Cancer, before and after Surgery

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Vocal cord cancer (1 of 4)

Squamous cell carcinoma, right vocal cord (left of image), standard light.

Vocal cord cancer, 1 week after surgery (2 of 4)

One week after laser excision. See irregular granulation especially at lower margin of excision.