Laryngeal papillomatosis

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Laryngeal papillomatosis
SynonymsAdult papillomatosis, Juvenile papillomatosis, Recurrent respiratory papillomatosis, Squamous cell papillomatosis, Nonkeratinized papillomatosis
CT tracheal papillomatosis volume.png
Volumetric CT rendering of multiple tracheal papilloma (arrow).
Specialty Otorhinolaryngology   Blue pencil.svg
Complications Squamous cell carcinoma
CausesHPV infection

Laryngeal papillomatosis, also known as recurrent respiratory papillomatosis or glottal papillomatosis, is a rare medical condition in which benign tumor s (papilloma) form along the aerodigestive tract. [1] [2] There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis. [3] The tumors are caused by human papillomavirus (HPV) infection of the throat. The tumors may lead to narrowing of the airway, which may cause vocal changes or airway obstruction. [4] [5] Laryngeal papillomatosis is initially diagnosed through indirect laryngoscopy upon observation of growths on the larynx and can be confirmed through a biopsy. [6] [7] [8] Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence. [9] Due to the recurrent nature of the virus, repeated treatments usually are needed. [7] [9] [2] [10] Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases. [7] [10] The evolution of laryngeal papillomatosis is highly variable. [4] [1] Though total recovery may be observed, it is often persistent despite treatment. [11] [8] [1] The number of new cases of laryngeal papillomatosis cases is at approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually. [1] [6] [7] [12]

A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discovering treatments for it, except by the government granting economically advantageous conditions to creating and selling such treatments. Orphan drugs are ones so created or sold.

Neoplasm abnormal mass of tissue as a result of abnormal growth or division of cells

A neoplasm is a type of abnormal and excessive growth, called neoplasia, of tissue. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass. When it forms a mass, it may be called a tumor.

Papilloma cell type benign neoplam that is composed of epithelial tissue on papillae of vascularized connective tissue

A papilloma is a benign epithelial tumor growing exophytically in nipple-like and often finger-like fronds. In this context papilla refers to the projection created by the tumor, not a tumor on an already existing papilla.


Signs and symptoms

A common symptom of laryngeal papillomatosis is a perceptual change in voice quality. More specifically, hoarseness is observed. [4] [5] As a consequence of the narrowing of the laryngeal or tracheal parts of the airway, shortness of breath, chronic cough and stridor (i.e. noisy breathing which can sound like a whistle or a snore), can be present. [4] [5] As the disease progresses, occurrence of secondary symptoms such as dysphagia, pneumonia, acute respiratory distress syndrome, failure to thrive, and recurrent upper respiratory infections can be diagnosed. [4] [5] The risk of laryngeal papillomatosis spreading to the lungs is higher in the juvenile-onset than the adult-onset. [3] In children, symptoms are usually more severe and often mistaken for manifestations of other diseases such as asthma, croup or bronchitis. Therefore, diagnosis is usually delayed. [8] [5]

Hoarse voice voice disorder

A hoarse voice, also known as dysphonia, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the throat. Hoarseness is often a symptom of problems in the vocal folds of the larynx. It may be caused by laryngitis, which in turn may be caused by an upper respiratory infection, a cold, or allergies. Cheering at sporting events, speaking loudly in noisy situations, talking for too long without resting one's voice, singing loudly, or speaking with a voice that's too high or too low can also cause temporary hoarseness. A number of other causes for losing one's voice exist, and treatment is generally by resting the voice and treating the underlying cause. If the cause is misuse or overuse of the voice drinking plenty of water may alleviate the problems.

Larynx voice box, an organ in the neck of amphibians, reptiles, and mammals

The larynx, commonly called the voice box, is an organ in the top of the neck of tetrapods involved in breathing, producing sound, and protecting the trachea against food aspiration. The larynx houses the vocal folds, and manipulates pitch and volume, which is essential for phonation. It is situated just below where the tract of the pharynx splits into the trachea and the esophagus. The word larynx comes from a similar Ancient Greek word.

Trachea cartilaginous tube that connects the pharynx and larynx to the lungs

The trachea, colloquially called the windpipe, is a cartilaginous tube that connects the pharynx and larynx to the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends from the larynx and branches into the two primary bronchi. At the top of the trachea the cricoid cartilage attaches it to the larynx. This is the only complete tracheal ring, the others being incomplete rings of reinforcing cartilage. The trachealis muscle joins the ends of the rings and these are joined vertically by bands of fibrous connective tissue – the annular ligaments of trachea. The epiglottis closes the opening to the larynx during swallowing.


Laryngeal papillomatosis is caused by human papillomavirus (HPV) infection, most frequently genotypes 6 and 11 [13] although genotypes 16, 18, 31, and 33 have also been implicated. [7] HPV-11 is associated with more aggressive forms of papillomatosis, which may involve more distal parts of the tracheobronchial tree. [7] The mode of viral innoculation is hypothesized to vary according to age of disease onset. [13] [14] The presence of HPV in the respiratory tract does not necessarily result in the development of laryngeal papillomatosis. Other factors that could be involved include immunodeficiency or other similar infections. For example, laryngeal papillomatosis may become more aggressive due to the presence of certain viruses (e.g., herpes simplex virus, Epstein-Barr virus). [2]

Human papillomavirus infection

Human papillomavirus infection is an infection by human papillomavirus (HPV). Most HPV infections cause no symptoms and resolve spontaneously. In some people, an HPV infection persists and results in warts or precancerous lesions. The precancerous lesions increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, or throat. Nearly all cervical cancer is due to HPV with two types, HPV16 and HPV18, accounting for 70% of cases. Between 60% and 90% of the other cancers mentioned above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

The disease is typically separated into two forms, juvenile and adult papillomatosis, based on whether it develops before or after 20 years of age. [1] [7] The juvenile form is generally transmitted through contact with a mother’s infected vaginal canal during childbirth. [14] Less is known about transmission in the adult form of this disease, though oral sex has been implicated as a potential mode of transmission. [13] [14] However, it is uncertain whether oral sex would directly transmit the virus [14] or activate the dormant virus that was transmitted at childbirth. [14] [13]

Oral sex sexual activity involving the stimulation of the genitalia by the use of the mouth

Oral sex, sometimes referred to as oral intercourse, is sexual activity involving the stimulation of the genitalia of a person by another person using the mouth or throat. Cunnilingus is oral sex performed on female genitals, while fellatio is oral sex performed on a penis. Anilingus, another form of oral sex, is oral stimulation of a person's anus. Oral stimulation of other parts of the body is usually not considered oral sex.

In general, physicians are unsure why only certain people who have been exposed to the HPV types implicated in the disease develop laryngeal papillomatosis. In the case of the juvenile form of the disease, the likelihood of a child born of an infected mother developing laryngeal papillomatosis is low (between 1 in 231 to 1 in 400), [15] even if the mother’s infection is active. [13] Risk factors for a higher likelihood of transmission at childbirth include the first birth, vaginal birth, and teenage mother. [14] [13]

There are three big risk factors that contribute to the acquirement of the juvenile variant. These include: [16]


Laryngeal papillomatosis can be diagnosed through visualization of the lesions using one of several indirect laryngoscopy procedures. [6] [8] In indirect laryngoscopy, the tongue is pulled forward and a laryngeal mirror or a rigid scope is passed through the mouth to examine the larynx. [12] [6] Another variation of indirect laryngoscopy involves passing a flexible scope, known as a fiberscope or endoscope, through the nose and into the throat to visualize the larynx from above. [12] [8] This procedure is also called flexible fiberoptic laryngoscopy. [12]

The appearance of papillomas has been described as multiple or rarely, single, white growths with a lumpy texture similar to cauliflower. [12] [7] Papillomas usually present in the larynx, especially on the vocal folds and in the space above the vocal folds called the ventricles. [17] [18] [1] They can spread to other parts of the larynx and throughout the aerodigestive tract, from the mouth to the lower respiratory tract. [1] [7] [17] Spread to regions beyond the larynx is more common in children than adults. [17] Growths tend to be located at normal junctions in squamous and ciliated epithelium or at tissue junctions arising from injury. [1] [17] [18]

A confirmatory diagnosis of laryngeal papillomatosis can only be obtained through a biopsy, involving microscopic examination and HPV testing of a sample of the growth. [7] [6] Biopsy samples are collected under general anesthesia, either through direct laryngoscopy or fiberoptic bronchoscopy. [6] [7]


Little is known in terms of effective means of prevention. Due to the low likelihood of transmission even from an infected mother, it is not recommended to expose the mother and child to the additional risks of caesarean section to prevent the transmission of this disease during vaginal childbirth. [13] Opting for a caesarean section does not guarantee that transmission will not still occur. [14]


As of 2014 there was no cure for laryngeal papillomatosis, and treatment options aimed to remove and limit the recurrence of the papillomas. [9] Repeated treatments are often needed because of the recurrent nature of the virus, especially for children, as the juvenile form of laryngeal papillomatosis often triggers more aggressive relapses than the adult form. [9] [2] [7] [10] Between recurrences, voice therapy may be used to restore or maintain the persons's voice function. [12]


The first line of treatment is surgery to remove papillomas. [7] [10] Typically performed using a laryngeal endoscopy, surgery can protect intact tissues and the individual’s voice, as well as ensure that the airway remains unobstructed by the disease. [2] However, surgery does not prevent recurrences, and can lead to a number of serious complications. [9] [7] [10] Laser technology, and carbon dioxide laser surgery in particular, has been used since the 1970s for the removal of papillomas; however, laser surgery is not without its risks, and has been associated with a higher occurrence of respiratory tract burns, stenosis, severe laryngeal scarring, and tracheoesophagyeal fistulae. [9] [2] [7] [10] Tracheotomies are offered for the most aggressive cases, where multiple debulking surgery failures have led to airways being compromised. [2] [7] The tracheotomies use breathing tubes to reroute air around the affected area, thereby restoring the person's breathing function. Although this intervention is usually temporary, some people must use the tube indefinitely. [8] This method should be avoided if at all possible, since the breathing tube may serve as a conduit for spread of the disease as far down as the tracheobronchal tree. [2] [7]

A microdebrider is a tool that can suction tissue into a blade, which then cuts the tissue. Microdebriders are gradually replacing laser technology as the treatment of choice for laryngeal papillomatosis, due to their ability to selectively suction papillomas while relatively sparing unaffected tissue. [2] [10] In addition to the lower risk of complications, microdebrider surgery also is reportedly less expensive, less time-consuming, and more likely to give the person a better voice quality than the traditional laser surgery approaches. [10]

Nonsurgical adjuvant treatment

For about 20% of people, surgery is not sufficient to control their laryngeal papillomatosis, and additional nonsurgical and/or medical treatments are necessary. [7] At the present time, these treatments alone are not sufficient to cure laryngeal papillomatosis, and can only be considered supplemental to surgery. [2] Some varieties of nonsurgical treatments include interferon, antiviral drugs (especially cidofovir, but also ribavirin and acyclovir), and photodynamic therapy. [9] [2] [7] [10] [12] The monoclonal antibody against Vascular Endothelial Growth Factor (VEGF), Bevacizumab has shown promising result as an adjuvant therapy in the management of recurrent respiratory papillomatosis. [19] [20]


The evolution of laryngeal papillomatosis is highly unpredictable and is characterized by modulation of its severity and variable rate of progression across individuals. [4] [1] While instances of total recovery are observed, the condition is often persistent and lesions can reappear even after treatment. [8] [1] [11] Factors that might affect the clinical course of the condition include: the HPV genotype, the age at onset, the elapsed time between the diagnosis and first treatment in addition to previous medical procedures. [7] [17] [1] Other factors, albeit controversial, such as smoking or the presence of gastroesophageal reflux disease might also play a role in the progression of the disease. [17] [3]

The papillomas can travel past the larynx and infect extralaryngeal sites. [4] In more aggressive cases, infection of the lungs can occur with progressive airway obstruction. [4] [5] Although rare (less than 1% of people with laryngeal papillomatosis), transformation from a benign form to a malignant form is also observed. [4] [5] Death can result from these complications (morbidity rate is around 1-2%). [4]


Laryngeal papillomatosis is a rare disease with a bimodal distribution based on age of incidence. [1] The incidence, or number of new cases, of laryngeal papillomatosis cases is at approximately 4.3 cases per 100 000 children and 1.8 cases per 100 000 adults annually. [7] [6] [12] [1] The incidence of laryngeal papillomatosis in children peaks before the age of 5, though the term juvenile papillomatosis refers to all cases occurring before the age of 20. [1] [7] The incidence of adult laryngeal papillomatosis, which has an onset after the age of 20, peaks between the ages of 20 and 40. [7] [1] While there are no gender differences in the incidence of laryngeal papillomatosis in children, adult laryngeal papillomatosis occurs more frequently in males than in females. [7] [17] [1] The incidence of laryngeal papillomatosis also varies according to factors such as socioeconomic status, such that higher rates are observed in groups having a lower socioeconomic status. [7]


As of 2013 there had been case reports of using HPV vaccines to prevent laryngeal papillomatosis but it was not known if this was effective. [21] As of 2015 use of the measles-mumps-rubella vaccine to reduce rate of recurrences had been investigated, but had not yielded significant results. [2]

See also

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