Laryngeal papillomatosis

Laryngeal papillomatosis (papilloma) is a benign neoplasm, formativing from pavement or transitional epithelium and overhanging its surface as a papilla.Papillomatosis is a pathologic process, which is characterized by formation of multiple papillomas on any part of the skin or mucous membrane.

Laryngeal papillomatosis is happened to be as often as laryngeal polyps. They are the result of the proliferous process developing in epithelium and connective elements of mucous membrane under the influence of the Human Papilloma Virus. The isolated papillomas are very rare, in most cases they are the multiple formations, which can proceed not only in larynx, but at the same time on the soft male, palatine tonsils, lips, skin, mucous membrane of trachea. Papillomas anticipate very often, that's why this disease is named papillomatosis. More frequently Papillomas occur in early childhood and very seldom at grown-ups. Some cases of inborn papillomas are described.

Structurally, the papillomas represent the formations of two layers: papillary layer consisted of connective tissue and epithelial layer. At multiple children papillomas the connective plentifully vascularized elements are prevailed, as the elements of surface epithelium are prevailed in “older” papillomas of young men and grown-ups. Such papillomas have white and grey colors, in contrast with the first which are pink or red colors.

Laryngeal papillomatosis epidemiology

According to different authors, the papillomas make 15,9-57,5% in the structure of benign tumors. The disease can begin both in children's age and in adulthood. The juvenile papillomatosis is more often occured (in 87%), the symptoms of which are revealed in the first five years of life.

Prevention of laryngeal papillomatosis

Preventive events come down to dynamic surveillance over the patient, adherence the gentle voice mode by the patient, elimination of a professional harmfulness, treatment of a gastrointestinal tract concomitant pathology (reflux esophagitis) and respiratory tracts, inflammatory diseases of an ear, a throat and a nose, prevention of HPV infection.

Cause

The infection with the Human Papilloma Virus (HPV). Respiratory or laryngeal papillomatosis is basically caused (in 80-100% cases) by papillomaviruses by 11 (rare by 6) type. These are the viruses with oncogenic DNA, stimulating the proliferation of epithelial cells in the basal layer of the mucous membrane of the respiratory tract with the formation of papillomatous growths.
Laryngeal papillomatosis is mostly common for adult men and for children of first years of lives.

Classification

There are two types of papillomatosis according to age, severity of clinical manifestations and sources of infection:

• Adult-onset recurrent respiratory papillomatosis.
  Infection with HPV may occur via oral-genital and (or) oral-anal contact with a sexual partner who has clinical manifestations of human papillomavirus infection or with asymptomatic.
• Childhood-onset recurrent respiratory papillomatosis.
  Laryngeal papillomatosis is a quite rare, but a sore clinical manifestation of HPV infection, which is potentially life-threatening. As the newborns and also older children surrer from it. The infection is usually perinatal. The rapid course of the disease at young children (even at adults), leads to the development of respiratory stenosis, which requires reintervention, in some cases, monthly surgeries; many patients endure tens or even hundreds of endolaryngeal papillomas removal surgeries.

The prevalence: 1. limited 2. common 3. occlusive
The respiratory tract: 1. stenosis 0 degree 2. stenosis of Ia degree 3. stenosis of Ib degree 4. stenosis of the II degree 5. stenosis the III degree 6. stenosis of the IV degree
The violation of the speech: 1. not broken 2. easy violation 3. severe hoarseness 4.aphonia
The nature of the clinical course : 1. recurrence once a year; 2. recurrence 1-3 times a year; 3. constant recurrencing course.

Ways of infection

• oral-genital or oral-anal contact with a sexual partner with symptoms of papilloma infection or an asymptomatic virus carrier;
• from the sick mother to the fetus during the passage through the birth canal;

The pathogenesis of laryngeal papillomatosis

The disease is characterized by rapid course, a tendency to relapse is often accompanied by stenosis of the larynx lumen. The papilloma develops at the adult age of 20-30, or at the old age. The frequent relapses are forced to the numerous surgical interventions, therefore the cicatricial deformations of the larynx are developed among most patients, sometimes leading to the stricture and deterioration of voice function. Bronchial pneumonia may develop among the children, moreover the spread of papillomas in the trachea is diagnosed in 17-26%, in the bronchi and lungs - in 5% of cases. The last one is considered a poor prognostic sign concerning the malignancy.
The disease is accompanied by a decrease of general and local immunity, the violation of its humoral, changes of hormonal and metabolic status.

The symptoms of laryngeal papillomatosis

• hoarseness up to its full loss
• difficulty of breath
• asthma (in serious cases)
• cough
• shortness of breath

The main clinical sign of the laryngeal papillomatosis is hoarseness and breathing disorders. The severity of the disease is caused with frequent relapses, which can lead to stenosis of the larynx, the possibility of papillomas spread into trachea and bronchi with subsequent development of pulmonary insufficiency and malignancy.

The symptoms of laryngeal papillomatosis are determined by the patient's age, localization and incidence of tumors. Common diffuse forms are mostly observed in small children, whereas older children have papillomas with a more limited localization (circumscripta papillomatosis). Adults have more common papillomas on vocal folds, characterized by hyperkeratosis.

The main symptom among children and adults is increasing hoarseness, reaching full aphonia. At the same time children have increasing phenomena respiratory disorders, shortness of breath during phisical exercises and other signs of hypoxia. The signs of dyspnoea increase, the spasms of the larynx, stridor and symptoms of suffocation appear. It can lead to child's death, if emergency measures are not accepted.

In some cases, the attacks of asphyxia suddenly arise during the trivial intercurrent inflammatory disease of the larynx, developing with its concomitant swelling. The younger the child, the more dangerous these attacks, because of the significant development of the loose connective tissue in the subglottic place, the small size of the respiratory tract and at young children, papillomatosis diffuses and evolves very quickly. All these risky factors of asphyxia should be considered at monitoring these children. Asthma is not observed at adults, and the only symptom indicating a substantial formation in the area of the glottis is hoarseness.

Diagnosis of laryngeal papillomatosis
Mostly common used such diagnostic methods as:

• Molecular and histological research of biopsy material using methods of hybridization in situ and PCR;
• Direct laryngotracheotomy: it is performed using special flexible endoscopic techniques;
• Computed tomography;
• Microlaryngoscopy;
• Microlaryngostroboscopy;
• Additional methods of primary and clarifying diagnostics - photodynamic endoscopic and autofluorescence researches, allowing to define the clear boundaries of tumor growth and to identify hidden lesions of HPV.

Differential diagnostics

In case of microlaryngoscopy the picture of papillomatosis is very specific — the growth has the view of limited, often multiple papillary excrescences with fine-grain surface and in appearance it resembles a mulberry berry. Its color is dependent on the availability of vessels, the thickness and keratinization of the epithelium, so papilloma can change its color at different periods of the development from red, pale pink to white. The differential diagnosistics is carried out with tuberculosis and larynx cancer. The signs of malignancy are: ulceration of papillomas, the change of vascular pattern, a sharp restriction of vocal folds mobility in the absence of the scar process, submerged growth, keratosis. Difficulties of differential diagnosistics in papillomavirus present have elderly patients and patients with a large number of surgical interventions in their history. The final diagnosis is established by histological examination.

Treatment of laryngeal papillomatosis

The aims of treatment

• The removal of the primary cause – human papillomavirus - from the body;
• Elimination of respiratory tractstenosis;
• Reducing the number of recurrences;
• Preventing the spread of the process;
• Restore voice function.

Medication

During recent years the doctors often turn to non-surgical medical treatment of papillomatosis in children. The use of modern drugs allows significantly to lengthen the intervals between operations, and in some cases even refuse surgical intervention. Moreover, the most aggressive forms of papillomatosis are best amenable to the drug therapy, which are poorly treated surgically.

Such successes became possible when the causative agent had been identified - the human papilloma virus, in particularly its certain types: 6 and 11 types.
Currently the most popular are interferons (interal, reaferonum), the drugs are used which promote the body to produce its own interferon (cycloferon, Amiksin, etc.). It is established that interferons are the important component of antiviral immunity, and this is the asnwer of their choice to treate the patients with laryngeal papillomatosis.
The choice of another drugs group as antiviral is quite clear, because the disease has a viral nature. Among the antiviral agents, which are used for the treatment of respiratory papillomatosis there are cidofovir, acyclovir, etc. Allokin-alpha has become popular as a quite new antiviral drug.

They also apply the drugs which slow the cells reproduction - cytostatic agents. As they are superpotent substances (they are used in oncology) to treat laryngeal papillomatosis at children, they are used only topically: swab the surface of the vocal folds after the papillomas removal or instead of surgical treatment.
Podophyllin is the most widely used for this purpose, a herbal drug consisted of a mixture with different compounds obtained from rhizomes and roots of podophyllum thyroid. The juice of Kalanchoe is also used for lubrication of the vocal folds.

A new group of drugs, so-called cytokine therapy, is more and more widely used during last years. Among the drugs of this group for the treatment of respiratory papillomatosis roncoleukin is applied.

Antibiotics play an important part in the treatment of postoperative laryngitis, local and general anti-inflammatory therapy. They accept the local application of cytostatics, antiviral drugs and drugs which affect the level of estrogen metabolites and etc. On the base of the immune status study they hold the immune correction.

Surgical treatment of Laryngeal papillomatosis

To remove papillomas is used:

• electrocoagulation (the growth impact by electric current)
• cryotherapy (the growth destruction using low temperatures)
• ultrasonic disintegration (the growth destruction using high intensity ultrasound)
• CO2 laser and argon plasma coagulation (the growth impact by laser beam)

But during the operation only the papillomavirus is deleted, the virus itself remains in the body.

An effect in the laryngeal papillomatosis treatment is possible to obtain only by a reasonable combination of different methods. If we do only a surgical removal of papillomas without antiviral therapy, the possibility to keep a more or less good larynx, alas, is probably unlikely.

Unfortunately, the most common way to help the child at papillomatosis is currently just surgical. The method is extremely simple: to remove papillomatous growths, and thus to create conditions for optimal breathing. It is clear that the surgical intervention has no therapeutic effects on the development of the disease.

Therefore it is no surprise that children have several surgeries to remove the laryngeal papilloma: they can have five, ten, and even more than two dozen! Besides, the surgical treatment of laryngeal papillomatosis in children is always associated with additional tissues trauma and leads to two equally unpleasant results: first, frequently the operation increases the growth of new papillomas, and secondly, it always causes the formation of scar tissue, which further degrades the voice and breath.

So if it is possible, doctors try to use more gentle methods of treatment of Laryngeal papillomatosis. For example, a laser surgery that much less damages the larynx. An effective method of photodynamic therapy has been developed, when the special substance is administered endovenously - a photosensitiser, then the surface of papillomatous changed parts of the larynx are illuminated with the light of a certain frequency. These methods are used in the clinic of ENT diseases of St. Petersburg medical University named after academician I. P. Pavlov.

Prediction

The prediction is usually favorable with combination therapy.
Laryngeal papillomatosis is considered as a precancerous condition, malignizaciei occurs in 15-20% of cases, however, there may be a spontaneous remission.