Background

• Cancer of the larynx, or laryngeal cancer, refers to the larynx’s cancerous cell development, commonly known as the voice box. The larynx is a crucial organ located in the throat that houses the vocal cords, enabling speech production and helping with breathing by preventing food from entering the airway. 
• Laryngeal cancer typically develops in the squamous cells lining the inside of the larynx. It is often categorized based on the specific area within the larynx where the cancer originates, such as the supraglottic, glottis, or subglottis. The most prevalent type arises in the glottis, the middle part of the larynx containing the vocal cords. 
• Risk factors for developing laryngeal cancer include smoking tobacco, excessive alcohol consumption, prolonged exposure to irritants like chemicals or asbestos, and certain viral infections, such as human papillomavirus. Additionally, males are more likely to develop this type of cancer than females. 

Epidemiology

Incidence and Prevalence: 

• Global Incidence: Laryngeal cancer is among the most common cancers of the head and neck region, accounting for approximately 2-5% of all malignancies worldwide. 
• Geographical Variation: Incidence rates of laryngeal cancer can vary significantly across different regions and countries. Higher rates are often observed in developed countries, particularly in parts of Europe and North America. 

Risk Factors: 

• Tobacco Use: The main risk factors for laryngeal cancer are tobacco use, including smoking cigarettes. Long-term and heavy smokers have a significantly higher risk. 
• Alcohol Consumption: Prolonged irritation, heavy drinking, exposure to certain chemicals, and tobacco smoke are risk factors that can damage DNA in the cells of the larynx, initiating the cancer process. 

Anatomy

Pathophysiology

• Initiation: The exact cause of laryngeal cancer is not always clear, but it’s often associated with cumulative genetic mutations or alterations in the DNA of the cells in the larynx. Risk factors including prolonged irritation, heavy drinking, exposure to specific chemicals, and tobacco smoke can cause DNA damage in the larynx’s cells, which can start the cancer process. 
• Promotion: Following the initial genetic alterations, certain factors can promote the growth of these abnormal cells. Continued exposure to carcinogens, chronic inflammation due to irritants like smoking or alcohol, and other environmental factors can encourage the progression of these mutated cells. 
• Progression: The mutated cells start to proliferate and grow uncontrollably. Over time, these cells accumulate and form a mass or tumor within the larynx. This tumor can vary in size and location within the larynx, affecting different structures and potentially spreading to adjacent tissues. 
• Invasion: Cancer cells can invade nearby tissues and structures in the larynx, including the vocal cords, cartilage, muscles, and nerves. As the tumour expands, it may interfere with these structures’ regular functions, affecting breathing, swallowing, and speaking. 
• Metastasis: When cancer reaches an advanced stage, its cells can separate from the main tumour and travel through the circulation or lymphatic system to other areas of the body. Common sites of metastasis for laryngeal cancer include nearby lymph nodes in the neck, as well as distant organs like the lungs.

Etiology

• Tobacco and Alcohol Use: The two major risk factors for laryngeal cancer are strong alcohol use and tobacco use. Long-term exposure to these substances increases the likelihood of developing cancer in the larynx. 
• Exposure to Environmental Toxins: Occupational exposure to certain chemicals and toxins, such as asbestos, wood dust, paint fumes, and certain metals , can increase the risk of developing laryngeal cancer. 
• Chronic Irritation or Inflammation: Prolonged irritation of the larynx due to factors such as chronic acid reflux, poor vocal hygiene, repeated exposure to air pollutants, or chronic use of a poorly fitting denture that irritates the oral cavity might contribute to the development of laryngeal cancer. 
• Genetic Predisposition: There may be a hereditary component to laryngeal cancer development, although the specifics are not yet fully understood. 
• Poor Diet: The risk of laryngeal cancer may rise with a diet low in fruits and vegetables and deficient in key minerals, such as vitamins A and C. 

Genetics

Prognostic Factors

• Metastasis: The presence of distant metastases, where cancer has spread to other parts of the body, especially to distant organs, can significantly worsen the prognosis. 
• Histological Grade: The grade of the tumor, which reflects its level of abnormality and aggressiveness under the microscope, can influence prognosis. Well-differentiated tumors tend to have a better prognosis compared to poorly differentiated or undifferentiated tumors. 
• Tumor Size and Location: The size and specific location of the tumor within the larynx can impact prognosis and influence the choice of treatment. 

Clinical History

• Cancer of the larynx can occur at any age, but it is more commonly diagnosed in individuals who are over 40 years old.
• The risk of developing laryngeal cancer tends to increase with age, and it is more frequently seen in individuals between the ages of 55 and 75. However, cases in younger individuals, particularly due to factors such as smoking or exposure to certain environmental risks, are also reported. 

Physical Examination

• Laryngeal Examination: 
• Direct or indirect laryngoscopy may be performed by an otolaryngologist. 
• Direct laryngoscopy involves the use of a flexible or rigid scope to directly visualize the larynx. 
• Indirect laryngoscopy might involve the use of mirrors or video-assisted equipment to examine the larynx indirectly.  
• Imaging Studies: 
• Additional imaging tests, such as PET scans, MRI may be ordered to ascertain the cancer’s stage and extent based on the results and suspected extent of the disease. 
• Biopsy: 
• When unusual lesions or irregularities are detected, a medical procedure known as a biopsy might be conducted. This procedure entails extracting a tiny tissue sample from the affected region in the larynx. Subsequently, a pathologist examines this sample under a microscope to verify the existence of cancerous cells. 

Age group

Associated comorbidity

• Smoking and Alcohol Consumption: Chronic exposure to tobacco smoke and heavy alcohol consumption are the primary risk factors for developing laryngeal cancer. Smoking, especially, increases the risk significantly. People who both smoke and consume alcohol have a higher risk than those who do either alone. 
• Occupational Hazards: Exposure to certain workplace substances like asbestos, wood dust, paint fumes, and chemicals can increase the risk of developing laryngeal cancer. 
• Gender and Age: Laryngeal cancer is more common in men than women, and it tends to occur most frequently in people over the age of 55. 

Activities and Symptoms: 

• Voice Changes: Hoarseness or a change in the voice is one of the most common symptoms of laryngeal cancer. This may persist for a prolonged period. 
• Throat Pain or Difficulty Swallowing: Pain or difficulty while swallowing, or the sensation of something stuck in the throat, may be experienced. 
• Ear Pain: Pain in the ear may occur, though it’s not necessarily a common symptom. 
• Persistent Cough or Sore Throat: Laryngeal cancer may be indicated by a chronic cough or sore throat that either doesn’t go away or grows worse with time. 
• Breathing Difficulties: Advanced laryngeal cancer might cause breathing difficulties due to obstruction in the airway. 
• Weight Loss and Fatigue: Unexplained weight loss and fatigue may accompany advanced stages of laryngeal cancer. 

Associated activity

Acuity of presentation

• Hoarseness or Changes in Voice Quality: A laryngeal cancer early warning indication could be persistent hoarseness or changes in voice quality that continue longer than a few weeks. This is frequently the most prevalent first symptom. 
• Throat Pain or Soreness: Some individuals may experience persistent throat pain or a sore throat that doesn’t improve with time or treatment. 
• Difficulty Swallowing: As the tumour expands, it may block the larynx’s ability to transmit liquids or food, leading to difficulty or pain while swallowing (dysphagia). 
• Persistent Cough or Coughing up Blood: Coughing that doesn’t resolve and may be accompanied by blood in the sputum can be a symptom of advanced laryngeal cancer. 
• Ear Pain: Pain in the ears might be experienced as the cancer progresses, due to nerve involvement or spread of the tumor to adjacent structures. 
• Breathing Problems: In advanced cases where the tumor obstructs the airway, individuals may have trouble breathing, noisy breathing (stridor), or even shortness of breath. 
• Enlarged Lymph Nodes: If the cancer has progressed to these areas, the neck lymph nodes may swell or expand. 

Differential Diagnoses

• Benign Vocal Cord Lesions: Conditions like vocal cord polyps, nodules, cysts, or granulomas can cause voice changes and hoarseness like those seen in laryngeal cancer. 
• Laryngeal Trauma: Injury to the larynx due to intubation, direct trauma, or other causes can lead to symptoms like those of laryngeal cancer. 
• Gastroesophageal Reflux Disease: Irritation, vocal cord inflammation, and vocal abnormalities can result from persistent stomach acid reflux into the throat and larynx. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• Surgery: Depending on the stage and location of the cancer, surgery might involve removing a portion of the vocal cords, partial laryngectomy, or total laryngectomy. After a total laryngectomy, the patient loses the ability to speak normally and may need alternative methods of communication, such as speech therapy or voice prosthesis. 
• Radiation Therapy: This treatment uses high-energy beams to kill cancer cells. It can be used alone or in combination with surgery. For early-stage laryngeal cancer, radiation therapy might be the primary treatment or used post-surgery to eliminate any remaining cancer cells. 
• Chemotherapy: To increase the efficacy of radiation therapy, it can be used in conjunction with it. 
• Targeted Therapy: This treatment involves drugs that target specific abnormalities present within cancer cells, often with fewer side effects compared to chemotherapy. Targeted therapies might be used for certain types of advanced laryngeal cancers, especially when other treatments have not been successful. 
• Immunotherapy: This treatment boosts the body’s immune system to recognize and attack cancer cells. Immunotherapy drugs, such as immune checkpoint inhibitors, are used to treat some types of advanced laryngeal cancers. 
• Speech and Swallowing Therapy: For patients who undergo surgery affecting their vocal cords or larynx, speech therapy is crucial to help them regain communication skills. Swallowing therapy may also be necessary to learn how to swallow properly after certain types of treatment. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-laryngeal-cancer

• Avoidance of Tobacco: Smoking and using other tobacco products significantly increase the risk of developing laryngeal cancer. To prevent this kind of cancer, it is imperative that smokers give up and stay away from second-hand smoke. 
• Limit Alcohol Consumption: Heavy alcohol consumption is another significant risk factor for laryngeal cancer. Reducing or avoiding alcohol intake can help lower the risk of developing this condition. 
• Protection from Environmental Toxins: Minimizing exposure to industrial fumes, chemicals, and other environmental toxins that can irritate the larynx may lower the risk of cancer. This might involve using protective gear in certain occupational settings. 
• Voice Care: Individuals who rely heavily on their voices professionally (such as singers, teachers, public speakers) should practice proper voice care techniques. This includes avoiding excessive strain on the vocal cords, staying hydrated, and using amplification when needed to reduce strain. 
• Regular Medical Check-ups: Periodic medical check-ups and screenings can help in early detection of any precancerous or cancerous changes in the larynx. Early detection greatly improves treatment outcomes. 
• Immunization against HPV: A human papillomavirus infection raises the risk of developing some forms of laryngeal cancer. Getting vaccinated against HPV can lower the risk by preventing infection. 
• Follow Medical Advice: For individuals who have undergone treatment for laryngeal cancer, following medical advice, attending regular follow-up appointments, and adhering to prescribed therapies are crucial for recovery and reducing the chances of recurrence. 

Targeted therapy in treating laryngeal cancer

• cetuximab (Erbitux) 
• Cetuximab is a monoclonal antibody used in the treatment of various cancers, including certain types of head and neck cancers like laryngeal cancer. It works by targeting a protein known as the epidermal growth factor receptor (EGFR) that is found on the surface of some cancer cells. 
• In the treatment of laryngeal cancer, It is possible to combine cetuximab with other treatments like chemotherapy or radiation therapy. 

Immunotherapy in treating laryngeal cancer

• pembrolizumab (Keytruda) & nivolumab (Opdivo) 
• Pembrolizumab and nivolumab are both immune checkpoint inhibitors that target the PD-1 receptor. These medications function by boosting the immune system’s capacity to identify and combat cancerous cells. 
• Clinical trials and studies have investigated the effectiveness of pembrolizumab and nivolumab in treating laryngeal cancer, especially when the cancer has reappeared or spread after first receiving treatment. 

surgery-in-treating-laryngeal-cancer

• Surgery: The type of surgical procedure employed depends on the tumor’s size and its specific location within the body. It might involve: 
• Partial laryngectomy: Removing part of the larynx. 
• Total laryngectomy: Removing the entire larynx. 
• Neck dissection: If the cancer has spread, the neck lymph nodes will be removed. 
• Radiation Therapy: High-energy radiation is utilized to eliminate cancerous cells and can be applied independently or in conjunction with surgical procedures. Both external beam radiation and internal radiation techniques could be utilized in treatment. 
• Chemotherapy: Chemotherapy entails the utilization of medications to eliminate cancerous cells or hinder their proliferation. This treatment method can be employed independently or in conjunction with radiation therapy, a combined approach known as chemoradiation. 
• Targeted Therapy or Immunotherapy: These newer treatments target specific abnormalities within cancer cells or boost the body’s immune system to fight cancer. 

role-of-management-in-treating-laryngeal-cancer-specialty

• Diagnosis: 
• Clinical Examination: A thorough examination by an ENT specialist involves checking the larynx, neck, and throat for any abnormalities or signs of cancer. 
• Imaging Tests: Imaging tests like X-rays, PET scans, MRI scans, CT scans help in determining the extent of the cancer. 
• Biopsy: To verify whether cancer cells are present, a biopsy is carried out. A small tissue sample is taken from the affected area and examined under a microscope. 
• Staging: 

The tumor’s size is used to assess the cancer’s stage, its extent, and whether it has spread to nearby tissues or lymph nodes. Staging helps in planning the appropriate treatment. 

• Surgery: Depending on the stage and location of the cancer, surgery might involve removing part or all the larynx. 
• Radiation Therapy: Tumours can be shrunk, or cancer cells killed with high-energy radiation. 
• Chemotherapy: Drugs are used to either destroy or inhibit the growth of cancer cells. Chemotherapy can be applied both on its own and in conjunction with other medical procedures. 
• Targeted Therapy and Immunotherapy: These newer treatments target specific abnormalities within cancer cells or boost the body’s immune system to fight cancer. 
• Treatment Implementation: 

The treatment plan selected is implemented in accordance with the individual requirements and health condition of the patient. 

Follow-up visits and monitoring for potential side effects or complications are essential during this phase. 

• Rehabilitation: 

After treatments like surgery or radiation therapy, rehabilitation may be necessary to help patients adapt to changes in speech or swallowing abilities. 

Speech therapy and swallowing exercises may be recommended to regain or improve function. 

• Ongoing Monitoring and Support: 

Routine follow-up visits and examinations are essential to oversee and detect any indications of cancer reoccurrence or potential complications. 

Patients grappling with the emotional and psychological challenges of a cancer diagnosis and treatment can find significant benefits from psychological support, counselling, or participation in support groups. 

• Survivorship Care: 

After successful treatment, patients continue to receive care focusing on their overall health, addressing potential long-term side effects, and maintaining a healthy lifestyle. 

Medication

Future Trends

Media Gallary

References

• Laryngeal Cancer – StatPearls – NCBI Bookshelf (nih.gov)