Laryngeal Cancer and Papillomatosis in Children

Juvenile laryngeal cancer is rare. Squamous cell carcinoma is the most prevalent type of laryngeal cancer in children. Children with laryngeal squamous cell carcinoma have survival rates similar to that of adults. To avoid a late diagnosis, physicians should consider laryngeal cancer in pediatric patients with hoarseness, dysphagia, and progressive airway obstruction.

Laryngeal cancer is classified into three categories based on the affected laryngeal area:

1. Glottic carcinoma (a type of vocal cord cancer)
2. Supraglottic cancer (affects the top region of the larynx, including the epiglottis, the cartilage that prevents food from entering the airways)
3. Subglottic carcinoma (a type of cancer that affects the subglottis, which is the lowest part of the larynx)

Rhabdomyosarcoma is the most common type of laryngeal cancer (soft tissue cancer) in children, but squamous cell carcinoma is more common in adults. Congenital subglottic hemangioma is a form of benign (nonmalignant) laryngeal tumor, which often occurs in children.

Although there are several forms of throat cancer, the risk factors and symptoms may be identical in many situations. Children must be treated by a doctor who specializes in pediatric oncology. The incidence of laryngeal cancer is less than 0.1 percent of all head and neck cancer cases in children.

Symptoms

• Cough
• Hoarseness or other changes in the voice
• Throat pain
• The sensation of a lump in the throat
• Swallowing difficulties
• Sore throat
• Unexplained weight loss
• Pain in the ear

Risk factors

The specific cause of laryngeal cancer development in children is unknown. Genetic mutations in laryngeal cells can cause uncontrolled cell proliferation. An increase in cell quantity and a reduction in cellular death can result in the buildup of malignant cells.

Some commonly known risk factors include:

• Human papillomavirus, which is a viral infection
• Gastroesophageal reflux disease (due to the regurgitation of stomach contents into the throat)
• Family history of throat cancer and head and neck cancer
• Smoking or chewing tobacco
• Heavy alcohol consumption

The otolaryngologist takes the complete personal and family medical history of the patient and performs a physical examination. Examination of the mouth and throat is done to detect any signs of cancer.

Radiological imaging techniques, such as barium swallowing, chest and neck X-rays, CT, MRI, and positron emission tomography scans, are used to find abnormal cancerous lesions.

Indirect fiberoptic laryngoscopy

• A laryngoscope (flexible tube with light and camera) is inserted into the nose, which goes way down to the throat. 
• This procedure is done either by numbing the nasal cavity with local anesthesia or general anesthesia is provided for children who are not cooperative. 
• The larynx and adjacent structures are well-inspected.

Direct laryngoscopy

• The laryngoscope is inserted through the mouth. 
• This procedure has the added benefit of allowing suspected tissue samples to be collected for laboratory analysis (biopsy). 
• This procedure may be done under the influence of general anesthesia.

The following laboratory tests are performed on the biopsy sample tissue:

Human papillomavirus (HPV) test 

• This test detects an HPV infection by DNA or RNA.
• Cells are extracted from the laryngeal mass and the DNA or RNA extracted from the cells is tested to see if the infection is caused by a type of HPV associated with laryngeal papillomatosis.

Immunohistochemistry

• In this test, antibodies are used to look for specific antigens (markers) in the tissue sample.
• Typically, antibodies are coupled to an enzyme or a luminous dye.
• The enzyme or dye is triggered once the antibodies attach to a specific antigen in the tissue sample and the antigen can then be observed under a microscope.
• This type of test is used to help detect cancer and distinguish one form of cancer from another.

Some treatments are in use, whereas others are being investigated in clinical studies.

Some of the treatment options include:

Laser treatment

• A laser beam (a narrow beam of bright light) is used in laser surgery to convert cancer cells into a gas that evaporates (dissolves into the air).
• Laser surgery can treat laryngeal cancer.

Radiation treatment

• A cancer treatment that employs high-energy X-rays or other forms of radiation to either kill or prevent cancer cells from developing.
• External radiation therapy uses a machine outside the body to direct radiation toward the cancerous location.
• Radiation treatment is often recommended to treat tumors that are prone to spread.

Immunotherapy

• A cancer treatment that employs the patient's immune system to combat the disease.
• Substances produced by the body or created in a laboratory are used to enhance or restore the body's natural anticancer defenses.

To treat laryngeal papillomatosis, the following immunotherapies are used:

Targeted therapy

• It is a cancer treatment in which medicines or other substances are used to locate and destroy specific cancer cells.
• A type of targeted treatment is monoclonal antibodies.
  • Monoclonal antibodies are immune system proteins created in the laboratory to treat a variety of disorders, including cancer.
  • These antibodies can bind to a specific target on cancer cells or other cells, which may aid in the growth of cancer cells.
  • These antibodies prevent the development of target cancer cells.
  • This antibody therapy can be given alone or in combination with other medications, which are toxic or radioactive and are delivered directly to cancer cells.

Interferon therapy

• Interferon inhibits cancer cell division and can halt tumor development.

A treatment clinical trial is a research study designed to enhance current medicines or gather information on novel treatments for cancer patients. When clinical studies report that a novel therapy outperforms the conventional treatment, the new treatment may be adopted as the standard treatment.

Because childhood cancer is uncommon, taking part in a clinical study should be encouraged. Some clinical trials are only available to people who have not yet begun therapy.

Laryngeal papillomatosis is also referred to as recurrent respiratory papillomatosis. Juvenile-onset laryngeal papillomatosis is more aggressive and the most common benign tumor of the larynx, which affects 4.3 per 100,000 children in the United States. 

Human papillomavirus types VI and XI are responsible for causing laryngeal papillomatosis. Mothers with HPV infect children during delivery with the virus that causes this type of laryngeal papillomatosis. 

It is also the second most common cause of childhood hoarseness. Although they can affect any area of the respiratory system, laryngeal papillomas are most commonly found in the larynx on the vocal cord borders and epiglottis.

Laryngeal papillomatosis in children is a more aggressive condition than in adults. They are noncancerous but can cause severe life-threatening respiratory complications and airway obstruction. Although noncancerous, they may undergo malignant transformation and cause squamous cell carcinoma. This transition is rare and seen in less than one percent of the cases.

Symptoms of laryngeal papillomatosis

• Progressively worsening hoarseness
• A strained or low-pitched voice
• Dyspnea (obstruction to the airway causing difficulty breathing)
• Stridor
• Chronic cough
• Shortness of breath 
• Dysphonia (difficulty speaking)
• Aphonia (complete loss of voice)
• Weak cry
• The sensation of a foreign body in the throat
• Choking
• Dysphagia (difficulty swallowing)
• Fail to grow and gain weight
• Acute respiratory distress
• Recurrent pneumonia
• Bronchiectasis (chronic lung disease)

Diagnosis

The otolaryngologist takes down the patient's detailed medical history and performs a physical examination to detect possible tumors. 

A laryngoscopy is performed on the child to view the larynx. A biopsy is also done to diagnose papillomatosis.

Although there is no cure for laryngeal papillomatosis, researchers are working toward surgical removal of the tumors with the help of potassium titanyl phosphate (KTP) laser and suppression of new tumor formation with drugs.

The following are a few treatment options:

Surgery

Surgical removal of the papilloma is the most advised treatment. In recent years, the KTP laser has been used for the surgical removal of papilloma. KTP laser is regarded as superior to other procedures such as carbon dioxide laser or microdebriders because it is more effective in removing tumors and reliable and does not cause injury to the larynx. 

Although surgical removal may improve the symptoms, reduce hoarseness, and prevent breathing difficulties, there is always a risk of recurrence of the papilloma. Some may require continuous surgeries because these tend to grow back. 

Targeted therapy

Studies have reported that the antiangiogenic drug bevacizumab can reduce the recurrence of papillomatous growth in the larynx. This drug is injected directly into the larynx or other surrounding structures. It restricts the growth of new blood vessels, preventing the generation of new tumors. Usually, this treatment is given in combination with laser surgery.

Studies regarding the drug's safety have reported that no complications associated with bevacizumab were noted for over a couple of years.

Adjuvant therapies

Several therapies are being used off-label and have been noted to have good responses.

• Interferon treatment is given to kill the virus that causes laryngeal papillomatosis.
• Vaccine against the human papillomavirus-9 used as a preventive measure has been studied as adjuvant therapy. 
• Proton pump inhibitors that control gastric acid may minimize metaplastic alterations in the epithelium, which could contribute to papilloma proliferation.