Laryngeal papillomatosis and current treatment R3 林世倉

Introduction

‧ Recurrent respiratory papillomatosis (RRP): Three clinical subgroups, including

pediatric cases, adults-onset cases, pediatric cases persist into adulthood.

‧ Most common sites of involvement: within the larynx

‧ Extralaryngeal sites: trachea, esophagus, lungs parenchyma, oropharynx, oral

cavity, nasal cavity, and other head and neck sites

‧ The most common benign laryngeal neoplasm to occur in children

‧ Defy most medical and surgical treatments

‧ Caused by human papilloma virus (HPV):

a. Double-stranded DNA with an icosahedral-shaped virion protein capsid with a

diameter 55 nm.

b. Genome consists of three regions: upstream regulatory region (URR), early (E,

E1-7, replication of viral genome) and late (L, L1-2, structural proteins)

regions

c. Infect basal cells of epithelium

d. More than 90 subtypes of HPV are known:

- Only viral subtype 6, 11 and, rarely, 16 and 18 have been noted in cases

of RRP

- High-risk subtypes 16 and 18: malignant transformation in

the laryngotracheal airway in cases of RRP ( high risk:

subtype 31, 45)

- Cutaneous warts: types 2 and 3

- Condylomas: HPV types 6 and 11

- Cervical cancer: HPV types (80%)16, 18, 31 and 45

‧ Laryngeal and genital HPV infection

a. The relationship between maternal genital condyloma acuminata in children

with RRP was first noted in 1956

b. A history of maternal condyloma was found in more than 30% of mother

bearing children with juvenile-onset laryngeal papillomatosis

c. In 1982, Mounts, et al. implicated HPV types 6 & 11 in the pathogenesis of

laryngeal RRP

d. Both caused by HPV subtypes 6 & 11 – vertical transmission in most of cases

(vaginal)

e. Rare in cesarean-delivered children

f. Adult-onset laryngeal papillomatosis- orogenital spread (clear evidence is

lacking). Junctional areas of cuboidal and cylindrical epithelium in both the

larynx and the uterine cervix may favor the existence of HPV infection.

‧ Milestones in the history of laryngeal human papillomavirus infection.

‧ Prevalence of HPV by PCR testing in the larynx

Histologic Features

‧ Pedunculated masses of slender projection of nonkeratinizing stratified squamous

epithelium supported by a core of highly vascular connective tissue stroma

‧ Cellular differentiation has been noted to be abnormal, with altered expression and

production keratins

‧ Histologically benign. Dysplasia and malignant changes may occur

Epidemiology

‧ The incidence: 4.3 per 100,000 people in the United States, 3.6 per 100,000 from

study in Denmark

‧ Bimodal age distribution

- the first peak: children younger than 5 years of age, 25% presenting

during infants

- the second peak: between the ages of 20 and 30 years

‧ Sex ratio

- juvenile-onset: equal

- adult-onset: M:F =2:1 to 4:1

‧ HPV 6 and HPV 11 are most commonly found in laryngeal papilloma lesions

‧ Typical site of infection at diagnosis: vocal folds

‧ Silverberg et al. (Danish): 7/1000 births to women with a maternal history of

genital warts resulted in RRP in their offspring

‧ Delivery times > 10 hours: Twofold of risk

Clinical appearance

‧ Initially hoarseness or aphonia, subsequently airway obstruction, stridor

‧ Less commonly, chronic cough, recurrent pneumonia, failure to thrive, dysphagia,

or acute life threatening events

‧ Tracheostomy may predispose children to distal tracheobronchial spread

Clinical course

‧ The course of the disease is unpredictable

- some patients recover after one laryngeal procedure

- in others the disease runs a relapsing course

‧ Two risk factors for frequent laryngeal procedures

a. young age at the onset of papilloma

b. a lesion extending to the anterior third of the vocal folds

‧ Children whose disease was diagnosed before the age of 3 years had a worse

prognosis

‧ Malignant transformation:

- rare event, 3% to 7% of the patients

- potential cofactor: irradiation therapy, smoking

Treatement

‧ Surgical management

- The mean number of surgical procedures per child is 4.4 per year in

juvenile-onset RRP

- The CO2 (λ=10600 nm) laser utilizing the micromanipulator: mainstay

of surgical management of pediatric RRP since 1970s

~ superficial vaporization

~ Scarring with subsequent airway obstruction, webbing, hoarseness,

possibility of endolaryngeal tube ignition, thermal injury to

surrounding tissue.

- Pulsed dye laser (λ=577 and 585 nm): effective in vascular

tissue

~ Franco et al.: pilot study on 41 adult cases (2002), most

effective for smaller, sessile lesions.

~ Less effective for larger, more exophytic lesions owing

to the limited depth of penetration of the laser

- Fiber-guided Nd:YAG laser (λ=1064 nm):

~ Philip et al. (2003), 5 patients (4-8 y/o): deep penetration (HPV-

infected basal cells), lower rate of recurrence, more precise treatment,

less smoke and effective suction (less infectious laser plume)

~ Sullivan et al. and Dagidin: damaging vocal cord mobility, scarring, or

acute postoperative edema with consecutive dyspnea

- Microdebrider

~ Pasquale et al.(2003), Petel et al. (2003), El-Bitar et al.(2002): more

rapid improvement in voice quality, shorter procedure times, and lower

overall procedure costs, no soft tissue complication

‧ Medical treatment

- Numerous adjuvant medical therapies are available: none of these

demonstrated a curative result

- Interferon (Interferon-α2a)

~ the most commonly accepted adjuvant medical therapy

for pediatric RRP

~ a family of nonspecific regulatory proteins associated

with a variety of antiviral, antiproliferative and

immunomodulating activities

~ given systemically by subcutaneous injection

~ eradication of disease in 30%-50% of patients

~ potential side effects and toxicities related to interferon:

a. neuropsychiatric complications and bone marrow

suppression

b. Neutropenia and thrombocytopenia may occur, along

with exacerbation of autoimmune disorders, renal

dysfunction, cardiac dysfunction, liver dysfunction,

alopecia, and impaired hormone levels leading to

infertility among women

c. significant rebound phenomenon may occur with

extensive regrowth of lesions after cessation of

interferon-α2a

- Retinoic acid

~ potentially affects epithelial maturation and the ability of the viral HPV

DNA to stimulate papillomatous growth

~ efficacy in selective patients

~ clinical trials have not demonstrated consistent, significant response

rates

- Photodynamic therapy

~ base on a selective uptake of hematoporphyrins by neoplastic cells and

subsequent exposure to specific wavelength laser light

~ Only variable results have been reported in the literature

- Indo-3 carbinol/diindolylmethane (I3C/DIM)

~ derived from eating cruciferous vegetables ( broccoli, cabbage, and

cauliflower)

~ estrogen metabolites: potential antipapilloma effect

~ significant regression in cervical intraepithelial neoplasia

~ Rosen et al.(1998): safety and efficacy of pre I3C/DIM in 18 children

(a small series)

- Cidofovir

~ nucleoside monophosphate analogue: inhibits viral DNA polymerase,

active against many DNA viruses such as herpes virus, EBV,

cytomegalovirus, adenovirus, and poxvirus

~ (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC)

~ FDA: cytomegalovirus retinitis in HIV-positive patients

~ injection after gross removal of the papillomas, max. doses: 5 mg/kg

~ treat papilloma at ant. commissure without risk of web formation

~ Van Custem et al. (1995): first report, Cidofovir in the treatment of

aerodigestive tract papillomas ( papillomatosis at upper esophagus and

hypopharynx ), disease free for 4 years

~ Snoeck et al. (1998): the use of Cidofovir in 17 adult patients with

laryngeal papillomatosis, 2.5 mg/mL every 2 weeks until a complete

clinical response

a. 10 patients remained disease free

b. 4 patients who relapsed responded to a repeat series of injections

and remained free of disease

c. 3 patients who were not cured of the papillomas required therapy

much less frequently than before

~ Pransky et al. (1999): 5 children who had required laser therapy more

frequently than once a month

a. one patient had complete remission

b. three pateintes had a significant decrease

c. one patient have had an “erratic” response

~ W. Peyton et al. (2003): 11 children who were requiring debridement of

papillomas at least every 6 weeks

a. 3 patients had impressive improvement

b. 2 patients had a partial response

c. 6 patients: cidofovir was considered ineffective

d. Cidofovir (5mg/mL) did not decrease the severity or frequency of

operative intervention for RRP in the majority of children in this

study

~ Details regarding the best treatment protocol for Cidofovir infection are

yet to be worked out

- Vaccine research

~ Pashley (2002): 11 patients with pediatric RRP underwent sequential

surgical debridement in the operating room with laryngeal injection of

mumps vaccine.

~ Remission occurred in 76% of patients

- Gene therapy

~ Sethi et al.(2003): direct gene transfer of the HSV-1TK (herpes simplex

virus type 1 thymidine kinase) into HPV-16-infected cells expressing E2

protein may result in cell death

Reference

1. Katherine A. Kendall: Current treatment for laryngeal papillomatosis. Current

Opinion in Otolaryngology & Head and Neck Surgery 2004, 12:157-159

2. Leena-Maija Aaltonen; Heikki Rihkanen; Antti Vaheri: Human Papillomavirus in

Larynx. Laryngoscope 112:700-707, 2002

3. Brian J. Wiatrak: Overview of recurrent respiratory papillomatosis. Current

Opinion in Otolaryngology & Head and Neck Surgery 2003, 11:433-441

4. De Clercq E, Holy A, Rosenberg I, et al.: A novel selective broad-spectrum anti-

DNA virus agent. Nature 1986, 323:464-467

5. Van Custem E, Snoeck R, VanRanst M, et al.: Successful treatment of a squamous

papilloma of the hypopharynx-esophagus by local infections of (S)-1-(3-hydroxy-

2-phonylmethoxypropyl) cytosine. J Med Virol 1995, 45:230-235.

6. W. Peyton Shirley, Brian Wiatrak: Is cidoforvir a useful adjunctive therapy for

recurrent respiratory papillomatosis in children. International Journal of Pediatric

Otorhinolarygology (2004) 68, 413-418.

7. Pransky SM, Magit AE, Dearns DB, et al: Intralesional Cidofovir for recurrent

respiratory papillomatosis in children. Arch Otolaryngol Head Neck Surg 1999,

125: 1143-1148

8. Snoeck R, Wellens W, Desloovere C, et al.: Treatment of severe laryngeal

papillomatosis with intralesional injections of Cidofovir. J Med Virol 1998,

54:219-225

9. Philip J, Andreas L, Ronald S, et al.: Preliminary report of enolaryngeal and

endotracheal laser surgery of juvenile-onset respiratory papillomatosis by

Nd:YAG laser and a new fiber guidance instrument. Otolaryngol Head Neck Surg

2004; 131:44-9

10. Pashley NR: Can mumps vaccine induce remission in recurrent repiratory

papilloma? Arch Otolaryngol Head Neck Surg 2002, 128: 783-786

11. Sethi N, Palefsky J: Treatment of human papillomavirus (HPV) type 16-infected

cells using herpes simplex virus type 1 thymidine kinase-mediated gene therapy

transcriptionally regulated by the HPV E2 protein. Hum Gene Ther 2003, 14:45-

57

Recurrent respiratory papillomatosis current status

By

Dr. T. Balasubramanian M.S. D.L.O.

Introduction:

Recurrent respiratory papillomatosis is a disorder of viral origin. It is associated

with multiple exophytic lesions present in the airway. It is a benign disorder, but

can cause airway complications with risk of malignant conversion. This disease is

difficult to treat because of its tendency to recur. Some patients may experience

spontaneous regression of the disease, while others may suffer from aggressive

papillomatous growth requiring multiple surgical interventions. The reasons for

this extremes in behaviour are not clearly understood.

Etiology: Human papilloma virus has been attributed as the causative organism.

Viral particles have never been consistently demonstrated in the papilloma

lesions even with electron microscopy. Use of viral probes have demonstrated

papilloma virus DNA in all the papilloma lesions studied.

Human papilloma virus: is a small DNA containing non enveloped icosahedral

(20 sided) capsid virus. The DNA is double stranded and circular.

Human papilloma virus

Depending on viral genetics 100 different types of human papilloma viruses have

been identified. Among the types affecting the aerodigestive and genital tracts

human papilloma virus types 6 and 11 have been associated with the lowest

malignant potential, where as human papilloma virus types 16 and 18 have the

greatest malignant potential. Children infected with human papilloma virus 11

have more obstructive airway early in the disease.

The human papilloma virus infects the basal layer of the mucosa. The viral DNA

enters the cells and gets transcribed into RNA. This RNA is translated into viral

proteins. After infection the viral DNA can either be actively expressed or can

exist as latent infection in the mucosa. In latent infections the mucosa remains

clinically and histologically normal. During latency, very little viral RNA is

present inside the cells. Reactivation of the virus can occur at any time leading to

symptoms.

The viral genome has 3 regions:

1. The upstream regulatory region

2. E region / Early region: The E genes are involved in oncogenes responsible for

active replication of the viral genome.

3. L region / Late region genes encode viral structural proteins.

Genome of Human papilloma virus

 

Human papilloma virus must have a means to reactivate the necessary host

replication genes to facilitate its own DNA replication. One growth factor known

to be associated with proliferation of epithelial cells is the epidermal growth

factor receptor. Papilloma virus induce epithelial proliferation by increasing the

level of expression of epidermal growth factor or its ligands. It may also increase

cell proliferation by interacting with p53 or other tumor suppressor proteins

inhibiting their normal functioning.

Host immune plays an important role in the pathogenesis of papilloma virus

infections. The patient's immunocompetence may influence the clinical course of

the disease. Both humoral and cellular immune responses may be compromised

in children with recurrent respiratory papillomatosis.

Epidemiology:

Recurrent respiratory papillomatosis may have its clinical onset either during

childhood or adulthood. Juvenile onset respiratory papilloma is more aggressive,

and adult onset disease may be little bit less aggressive. In children recurrent

respiratory papillomatosis is the most common benign neoplasm of the larynx.

Incidence may be very variable ranging from 2 - 3 / 100,000 population.

Observations suggest that most of these patients are first born child to young

primi gravida mothers. Primi gravida mothers are more prone for prolonged

second stage of labor causing increased exposure to the virus. It is common in

patients among low socioeconomic status. It is worthwhile to aggressively

manage genital papillomatous infections to prevent vertical transmission of the

infection from mother to child.

Transmission: The mode of transmission of human papilloma virus is unclear.

Studies have demonstrated the link between childhood onset recurrent

respiratory papillomatosis to mothers with genital papilloma virus infections; in

adults evidence suggests that it could be associated with oro genital contact.

Histology: It appears as sessile or pedunculated masses. It may be pink or

whitish in color. The masses consist of finger like projections of non keratinised

stratified squamous epithelium supported by a core of highly vascularised

connective tissue stroma. The basal layer may be either normal or hyperplastic

and mitosis is generally limited to this layer.

Histology of respiratory papilloma

Recurrent respiratory papilloma lesions occur often at anatomic sites in which

cilitated and squamous epithelium are juxtaposed. Common locations are:

1. Limen vestibuli of nose

2. Nasopharyngeal surface of soft palate

3. Laryngeal surface of epiglottis

4. Upper and lower margins of ventricle

5. Under surface of vocal folds

6. Carina

7. Bronchial spurs

Papilloma seen involving the vocal cord

Areas of transition from ciliated respiratory eithelium to native or metaplastic

squamous epithelium are commonly involved as seen in patients with

tracheostomies. Papilloma is seen at the stoma and in the mid thoracic trachea.

Children with broncho pulmonary dysplasia, in whom prolonged endotracheal

intubation may result interruption of the continous respiratory mucosal surface

causing increased incidence of respiratory papillomatosis.

Injury to respiratory mucosa caused by prolonged gastro oesophageal reflux

may also increase the risk of respiratory papillomatosis. Iatrogenic implantation

of papilloma may be prevented by avoiding injury to non diseased squamous or

ciliated epithelium adjacent to areas of frank papilloma.

Clinical presentation:

Hoarseness: of voice may occur depending on the position of the papilloma. It is

worse if the lesion is present in the vocal cord.

Stridor: occurs if the mass occludes the laryngeal inlet. Commonly inspiratory

becoming biphasic later.

Dysphonia: Children with respiratory papillomatosis always present with certain

degree of dysphonia

Physical examination:

Affected children should undergo complete physical examination. Airway

compromise if any must be given top priority. Tracheostomy will have to be

performed in cases of acute airway obstruction. Definitive diagnosis is possible

only after flexible fibre optic bronchoscopic examination.

Coltera and Derkay have evolved a staging system to stage recurrent

papillomatous lesions involving the respiratory tract.

Coltera-Derkay method of staging :

Clinical score:

1. Voice: Normal - 0, Abnormal - 1, Aphonia - 2

2. Stridor: Absent - 0, Present on activity - 1, Present at rest - 2

3. Respiratory distress - None - 0, Mild - 1, Moderate - 2, Severe - 3, Extreme - 4.

Anatomical score:

For each site - 0 = none, 1=surface lesion, 2= raised lesion, 3=bulky lesion.

Total score = Anatomical score + Total clinical score

Management:

Surgical: Microlaryngeal excision of the lesion is performed. Laser excision is

preferred in recurrent cases, and for cases where tracheal mucosa is involved.

Adjuvant treatment: Most commonly adopted criteria for initiating adjuvant

therapy is the requirement of more than 4 surgical procedures during a calender

year, distal multispread of disease.

Cidofovir: is a nucleoside analog that has antiviral activity against herpes family

of virus. This drug has been shown to induce apoptosis in human papilloma virus

infected cells.

Interferons: are manufactured by cells in response to a variety of stimuli,

including viral infection. Interferons when administered produce a blocking

effect on viral replication of RNA and DNA. It also alters the cell membrane

causing it become impervious to viral penetration. Hence interferon can be

adminstered as adjuvant.

Side effects of interferons include:

1. Flu like symptoms

2. Decreased growth rate of child

3. Leukopenia

4. Spastic diplegia

5. Thrombocytopenia

6. Alopecia

7. Pruritus

8. Fatigue

Photodynamic therapy:

Is based on the transfer of energy to a photosensitive drug. The drug used is

dihematoporphyrin ether (DHE). This drug has a tendency to concentrate within

papillomas more than in surrounding normal tissue. Patients are typically

treated intravenously with 4.25mg /kg of DHE before photoactivation with an

argon pump dye laser.

Ribavirin: is an antiviral drug used to treat pneumonia in infants caused by

respiratory syncytial virus has shown some promise in the treatment of

aggressive papillomatosis.

Celebrex (Celecoxib) Treatment of

Laryngeal Papilloma

This study has been terminated.

(03/01/2009,due to date close to termination of this funding/study period)

Sponsor:

Boston University

Collaborator:

National Institute on Deafness and Other Communication Disorders (NIDCD)

Information provided by (Responsible Party):

Zhi Wang, Boston University

ClinicalTrials.gov Identifier:

NCT00592319

First received: December 31, 2007

Last updated: August 24, 2012

Last verified: August 2012

History of Changes

Full Text View

  Purpose

Respiratory recurrent papilloma (RRP) is one of the most common benign tumors.

Surgical removal is the current management for RRP, but it is a very traumatic

procedure, and often leads to permanent voice dysfunction. In this study, we will

develop a new, combined RRP treatment with a pulsed dye laser (PDL) and Celebrex.

We will determine if Celebrex, a newly developed inhibitor of cyclooxygenase

(COX)-2, can provide a long-term inhibitory effect on RRP, therefore preventing RRP

from recurring. This combined strategy, if successful in this proposed study, will

provide a new and ideal "voice-preserving" therapy for RRP that will deliver long-

term efficacy in managing RRP.

Condition Intervention Phase

Laryngeal Drug: Celebrex Phase

Papilloma Device: PDL

Procedure: CO2 laser or

microsurgery

2

Study Type: Interventional

Study Design: Allocation: Randomized

Endpoint Classification: Efficacy Study

Intervention Model: Parallel Assignment

Masking: Open Label

Primary Purpose: Treatment

Official Title: Voice-preserving Treatment of Laryngeal Papilloma

Resource links provided by NLM:

Drug Information available for: Carbon   dioxide Celecoxib

U.S. FDA Resources

Further study details as provided by Boston University:

Primary Outcome Measures:

Number of Case With Papilloma Recurrence During a 12-month Follow up

[ Time Frame: 12-month follow up ] [ Designated as safety issue: No ]

Criteria for the recurrence: the site scoring >4, plus visible lesion found in

>50% of the treated tissue area, after surgery Description: The caculation of

the site scoring is based on a called Derkay's scoring system: to indicate how

many anatomic site involved, from the 0 (the best)to 13 (the worst),among a

total of 13 laryngeal sites such as epiglottis or right true vocal cords.

Secondary Outcome Measures:

Time Course (Month) With Papilloma Recurrence During 12-month Follow

up [ Time Frame: 12 months ] [ Designated as safety issue: No ]

The measuer is reported as time course (i.e., how many month) to see

papilloma recurrence if there is any such recurrence.

Enrollment: 10

Study Start Date: May 2005

Study Completion Date: July 2009

Primary Completion Date: July 2009 (Final data collection date for primary

outcome measure)

Arms Assigned Interventions

Experimental: PDL+Celebrex

endoscopic treatment with once-time PDL radiation

at 6.0-8.0 J on laryngeal papilloma, followed by oral

taking of 9-month Celebrex (100mg, BID), in 15

subjects

Drug: Celebrex

oral taking of Celebrex (100

mg, BID) for 9 months

Other Name: Celecoxib

Device: PDL

once time radiation on

laryngeal papilloma with PDL

, at 6.0-8.0 J

Other Name: 585 nm PDL

(cynosure Inc. Mass)

Active Comparator: standard surgery

once-time and routine surgery, with either of carbon

dioxide (CO2) laser radiation at 10.0-20.0 W or

"cold" surgery with microinstruments, in 15 subjects

Procedure: CO2 laser or

microsurgery

once-time surgery to remove

laryngeal papilloma

Other Name: ablation laser or

micro-instrumental surgery

Detailed Description:

RRP and its surgeries usually involves the vocal cords or other regions of the larynx,

thereby, resulting in a poor voice. Our previous studies have shown the efficacy and

safety of a microvascular targeting technique (MVT) for RRP treatment using the 585

nm PDL. This technique provides a less traumatic alternative to surgery. However,

postoperative recurrence of lesions still remains a problem because of microvascular

regrowth. This study is a continuation of our effort to develop a new and less

traumatic treatment for RRP. In this study, we will develop a new, combined RRP

treatment with PDL and Celebrex. We will determine if Celebrex, a newly developed

inhibitor of COX-2, can provide a long-term inhibitory effect on RRP through its anti-

angiogenic activity and the synergic effect produced with the laser therapy. The

hypothesis is that postoperative administration of Celebrex will provide a long-term

inhibitory effect on microvascular regrowth and on COX-2 enzyme, thereby,

preventing RRP from recurring after the PDL therapy. Our specific aim in this study

is to determine the synergic effect between PDL and Celebrex and long-term efficacy

of Celecoxib in preventing postoperative RRP recurrence. We will compare this new

combined strategy with traditional treatments in 30 adult patients. This is the first time

to combined this new laser MVT technique with a COX-2 inhibitor for microvascular

targeting therapy of RRP. This combined strategy, if successful in this proposed

study, will provide a new and ideal "voice-preserving" therapy for RRP that will

deliver long-term efficacy in managing RRP and will be safe and convenient enough

for use in out-patient treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years

Genders Eligible for Study:   Both

Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

1. 18 to 64 years of age

2. with laryngeal papillomas requiring surgical treatment

3. willingness to participate in the study

4. a signed informed consent form

Exclusion Criteria:

1. age less than 18 years

2. evidence of mental impairment so that the patient can not understand or sign

the consent form

3. malignant diseases such as laryngeal cancer

4. established coronary heart and artery disorder, cerebrovascular disease, and

other cardiovascular diseases

5. established diabetes, which requires (1) insulin treatment; or (2) more than 2

oral agents of medication; or (3) to have a baseline HgbA1c >8.0

6. hypertension, with ongoing blood pressure > 150 mg Hg systolic or to require

medication

7. family history with serious cardiovascular events and problems

8. any sign and evidence which in the opinion of cardiovascular physician

warrants exclusion of subject

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00592319

Locations

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

Boston University

National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

Principal Investigator: Wang Zhi, M.D Boston Medical Center  More Information

No publications provided

Responsible Party: Zhi Wang, Professor and Director, Boston University

ClinicalTrials.gov Identifier: NCT00592319     History of Changes

Other Study ID Numbers: RDC-006617A, R01DC006617

Study First Received: December 31, 2007

Results First Received: May 3, 2012

Last Updated: August 24, 2012

Health Authority: United States: Institutional Review Board

United States: Food and Drug Administration

United States: Federal Government

Keywords provided by Boston University:

Papilloma

pulsed dye laser

Celebrex

voice

Additional relevant MeSH terms:

Papilloma

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms

Celecoxib

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Molecular Mechanisms of

Pharmacological Action

Pharmacologic Actions

Anti-Inflammatory Agents, Non-

Steroidal

Analgesics, Non-Narcotic

Analgesics

Sensory System Agents

Peripheral Nervous System Agents

Physiological Effects of Drugs

Anti-Inflammatory Agents

Therapeutic Uses

Central Nervous System Agents

Antirheumatic Agents

ClinicalTrials.gov processed this record on December 15, 2013

IMAGE DESCRIPTIONS

This excision consists of a clearly exophytic tumor composed of numerous papillary

fronds.

The papillae are lined by a multilayered squamous epithelium which has undergone

dysplastic change. There are enlarged nuclei with disordered maturation and

significant crowding, features which are beyond that of the expected mild dysplasia

typical of HPV.

The squamous epithelium shows no maturation at all, consistent with a high grade

dysplasia. Additionally, there are mitoses near the surface.

Mitoses are numerous and involve all layers of the epithelium.

BACKGROUND

The non-keratinizing papilloma of the larynx can be divided in those arising in adults

or those in children. Human papillomavirus types 6 and 11 have been associated with

benign laryngeal papilloma.

The overall incidence of developing carcinoma in these lesions is about 2%, unless

there is a history of radiation, which increases this number to 14%. Transformation to

squamous cell carcinoma may result in loss of the HPV expression. One report

indicated that HPV-11 was the only type of HPV in all lesions comprising the

morphologic spectrum of papillomatosis progressing to carcinoma (Lele).

TREATMENT

Pharmacologic approaches (hormones, local corrosives, alkylating agents, interferon),

physical methods (electrocautery, ultrasound, laser, cryotherapy), and surgical

therapy, such as laser excision or microresection under microscope and open surgery

(Green)

PROGNOSIS

Despite surgical resection, papillomas tend to spread to surrounding tissues and recur.

The treatment of choice is complete resection of the lesion while preserving the

respiratory tract and protecting the voice. Lung and laryngeal carcinomas that may

develop are often diagnosed at a late stage with resultant low survival rates.

REFERENCES

Green, GE, Bauman, NM and Smith, RJ. (2000) Pathogenesis and treatment of

juvenile onset recurrent respiratory papillomatosis. Otolaryngol Clin North Am 33 ,

pp. 187-207.

Lele SM, et al. Molecular events in the progression of recurrent respiratory

papillomatosis to carcinoma. Arch Pathol Lab Med. 2002 Oct;126(10):1184-8.