Laryngeal (larynx) cancer

Overview

The larynx is located between the base of the tongue and the trachea in the throat. The vocal cords are located in the larynx and vibrate and generate a sound when air is directed against them. To produce a person's voice, the sound echoes via the pharynx, mouth, and nose.

Laryngeal malignancies account for one-third of all head and neck cancers and maybe a major cause of morbidity and death. Patients with a considerable smoking history are more likely to be diagnosed. They can affect several areas of the larynx, and the location of the involvement determines the presentation, patterns of spread, and treatment choices.

Early-stage illness is typically very treatable with either surgical or radiation treatment, with the larynx often preserved. Late-stage illness is associated with worse results, necessitates multimodal therapy, and is less likely to allow for laryngeal preservation.

Laryngeal (larynx) cancer definition

Laryngeal carcinoma is a kind of cancer that affects the larynx or voice box. Laryngeal cancer symptoms include hoarseness of the voice and a persistent painful throat or cough. A laryngectomy is a surgical procedure that removes part or all of the larynx.

In the United States, over 13,000 laryngeal malignancies are diagnosed each year, the vast majority of which are squamous cell tumors. Previously, laryngeal cancer was treated solely surgically; however, today's therapeutic approach is more focused on organ preservation with chemoradiation. Many studies demonstrate that this method yields outcomes comparable to complete laryngectomy. Endoscopic ways of treating laryngeal cancer are also available nowadays.

There are three main parts of the larynx:

• Supraglottis: The upper part of the larynx above the vocal cords, including the epiglottis.
• Glottis: The middle part of the larynx where the vocal cords are located.
• Subglottis: The lower part of the larynx between the vocal cords and the trachea (windpipe).

Epidemiology

In 2017, there were 13,150 new instances of laryngeal cancer, accounting for nearly one-third of all head and neck malignancies, with 3710 fatalities. The average age of patients is 65, with a larger number of males than females and blacks than whites. In recent years, age-adjusted incidence rates have fallen by roughly 2% per year, owing to lower cigarette smoking rates.

Approximately 98 percent of laryngeal malignancies occur in the supraglottic or glottic areas, with glottic cancers being three times more prevalent than supraglottic cancers and subglottic cancers accounting for only 2% of all instances. Early-stage malignancies are extremely treatable, with local control rates ranging from 90% to 95% for T1 glottic tumours and from 80% to 90% for early-stage supraglottic cancers.

Furthermore, such early-stage malignancies are usually amenable to surgical treatment that spares the vocal cords. Locally advanced tumors, on the other hand, have control rates ranging from 40% to 70%, with bulky and/or T4 disease frequently necessitating laryngectomy. However, advancements in technology have enabled for more laryngeal preservation and improved speech rehabilitation in individuals after laryngectomy.

Etiology

Smoking is the most major risk factor for laryngeal cancer, accounting for an estimated 70% to 95% of all occurrences. Any history of smoking increases risk, with present smokers having a greater relative risk than ex-smokers overall and a higher relative risk for supraglottic malignancies compared glottic tumors.

An link with strong alcohol intake has also been identified, albeit the independent effect of alcohol is unclear given that most instances include concurrent usage with cigarettes. Marijuana use may be a factor in younger patients. Unlike other head and neck cancers, the function of human papillomavirus (HPV) as a causal agent has not been demonstrated.

Other risk factors for laryngeal cancer include the following:

• Advanced age
• Diet low in green leafy vegetables
• Infection with HPV
• Diet rich in fats and salt-preserved meat
• Exposure to paint, asbestos, gasoline fumes and radiation

Pathophysiology

The great majority of laryngeal malignancies are well-differentiated squamous cell carcinoma. A small percentage of cases are squamous cell variations such as verrucous carcinoma, sarcomatoid carcinoma, and neuroendocrine carcinoma. Historically, verrucous and sarcomatoid carcinomas were thought to be radioresistant, however current evidence challenges this belief.

The pattern of spread is determined by the location of the main mass and the intrinsic lymphatic supply at that area. Laryngeal malignancies are classified as supraglottic, glottic, or subglottic, with pathogenesis and therapy varied depending on the subsite. 

Supraglottic

The supraglottis is split further into suprahyoid epiglottis, infrahyoid epiglottis, false vocal cords, aryepiglottic folds, and the arytenoids. Suprahyoid epiglottic tumors can develop exophytically and superiorly, reaching quite big before symptoms appear. In some circumstances, they may infiltrate inferiorly into the epiglottis tip and damage adjacent cartilage.

Infrahyoid epiglottic tumors, on the other hand, tend to develop circumferentially, including the aryepiglottic folds and infiltrating inferiorly into the false vocal cords. They also infiltrate the pre-epiglottic fat region anteriorly, followed by the vallecula and base of the tongue.

In contrast to glottic and subglottic tumors, lymphatic involvement is a pathologic feature of supraglottic malignancies, with 55 percent of patients having clinical signs of nodal metastases at presentation and 16 percent having contralateral involvement. Cancer primarily spreads to levels II, II, and IV of the cervical nodal chain to reduce the likelihood of involvement.

Locally progressed tumors have a greater risk of nodal metastasis, either because of bilateral tumor involvement, which raises the likelihood of lymphatic dissemination in the bilateral neck, or because of superior extension and invasion into the base of the tongue, vallecula, and pyriform sinus.

Glottic

The ventricle's apex indicates the transition from supraglottic to glottic larynx. The vocal cords are 3 to 5 mm thick and end posteriorly at a commissure with the vocal process. Because they have a limited lymphatic supply, they do not provide a danger of lymphatic involvement unless there is a supraglottic or glottic extension. Glottic malignancies are often limited to the anterior region of one vocal cord's top free margin. They can cause vocal cord fixation by using pure mass, intrinsic muscles and ligaments, or, in rare cases, the recurrent laryngeal nerve.

Subglottic

The subglottis extends superiorly from the free edge of the vocal cord to the inferior border of the cricoid cartilage and inferiorly to the superior border of the cricoid cartilage (or 10 mm below the apex of the ventricle). They also have a limited lymphatic supply, with drainage accumulating in cervical nodal levels IV and VI.

Symptoms

Patients are generally men who have a history of current or previous cigarette use. Hoarseness is a common early sign of glottic malignancies caused by vocal cord immobility or fixation, with swallowing difficulty and transferred ear pain suggesting advanced illness. In contrast, the most frequent early sign of supraglottic cancer is swallowing discomfort, with hoarseness suggesting advanced illness that has spread into the glottis.

Nodal metastases appear in the neck as fixed, hard, painless lumps. Weight loss, dysphagia, aspiration and its consequences, and airway compromise are common late symptoms across all subsites. The most important aspect of a physical examination is an invasive assessment of the main lesion, which may include indirect laryngoscopy, a mirror exam, and, in certain cases, fiberoptic endoscopy.

The goal is to determine the local extent of the tumor, taking note of the size and involvement of surrounding tissues, as well as the mobility of the vocal cord.

Direct laryngoscopy improves the capacity to identify the extent of illness as well as gather tissue specimens. A thorough neck examination is required not only to detect nodal metastases but also to determine the extent of the initial disease. Tenderness of the thyroid cartilage implies direct tumor extension, whereas firm fullness palpated slightly superior to the thyroid notch shows pre-epiglottic space invasion. 

Diagnosis

Other examinations are required in addition to the history, physical examination, and direct view of the larynx with tissue sampling indicated above. Tissue can be obtained in a variety of ways. The most useful are direct laryngoscopy biopsy of a suspected main lesion and fine-needle aspiration (FNA) of any suspected nodal illness.

Imaging of the main lesion and draining lymph nodes, generally using contrast-enhanced CT of the neck, is recommended for all laryngeal malignancies, whether presumed to be early or late stage. This study visualizes the lymphatics in the neck, as well as structures that cannot be assessed adequately with direct laryngoscopy, such as the subglottic region, as well as subtle signs of disease extension, such as minor invasion into the thyroid cartilage, all of which are critical for accurate staging.

To rule out distant metastases, a contrast-enhanced CT of the chest and a PET/CT scan would be performed if the illness was considered to be locally progressed. Suspected encroachment into the hypopharynx may need an esophagogastroduodenoscopy (EGD) and/or barium swallow, which can help distinguish the proper aerodigestive tissue of cancer origin.

Blood work is required prior to any operation, including a CBC, platelet count, liver and renal function, blood type, thyroid function, electrolytes, and albumin levels.

During the workup of laryngeal cancer, the following factors are considered:

• Vocal cord mobility
• Number of regions involved
• Presence of cervical or distant metastatic lesions
• Involvement of the base of the tongue
• Involvement of the paraglottic and pre-epiglottic space
• Involvement of the thyroid cartilage
• Involvement of the carotid artery and sheath
• Invasion of the esophagus
• Invasion of soft tissue and adjacent laryngeal muscles
• Involvement of neck lymph nodes

• MRI (magnetic resonance imaging): A technique that use a magnet, radio waves, and a computer to create a sequence of detailed images of locations within the body. This method is also known as nuclear magnetic resonance imaging (NMRI).
• PET scan (positron emission tomography scan): A method of locating malignant tumor cells in the body. In a vein, a little quantity of radioactive glucose (sugar) is injected. The PET scanner moves around the body, capturing images of where glucose is utilised in the body. Because malignant tumor cells are more active and take up more glucose than normal cells, they appear brighter in the image.
• PET-CT scan: A technique for combining images from positron emission tomography (PET) and computed tomography (CT) scans. The PET and CT scans are performed on the same equipment at the same time. The combined scans provide more comprehensive images of locations inside the body than either scan alone. A PET-CT scan can be used to assist identify diseases like cancer, plan treatment, or determine how well treatment is working.
• Bone scan: A test to see if there are any fast proliferating cells in the bone, such as cancer cells. A trace quantity of radioactive material is injected into a vein and circulated through the circulation. The radioactive substance accumulates in the bones of cancer patients and is identified by a scanner.
• Barium swallow: An x-ray sequence of the esophagus and stomach. The patient consumes a barium-containing beverage (a silver-white metallic compound). X-rays are obtained while the liquid clogs the esophagus and stomach. This is also known as an upper GI series.

Management

Early Stage Laryngeal Cancer

Early-stage laryngeal malignancies, including T1-2N0 illness, are successfully treated with a single, locally-directed treatment method, such as local radiation therapy or surgery.

T1-2N0 Glottic Cancer

Local radiation treatment or surgery is advised, with the choice of modality heavily influenced by physician experience and patient desire. Given the limited lymphatic drainage of the genuine glottis, these techniques all share a core tenet in that they solely treat the original tumor. Although there is no Level I data comparing the two techniques, local control rates from retrospective experience are comparable between surgical and RT treatments.

In many, but not all, of these malignancies, voice-saving surgery is an option. In one study, complete laryngectomy was the needed surgical technique in 10% of T1 tumors and 55% of T2 tumors. Transoral laser excision, laryngofissure, and partial laryngectomy are further options. Despite the lack of randomized evidence comparing surgery and RT, there is randomized data indicating that definitive RT outperforms transoral laser excision in terms of voice preservation.

T1-2N0, Selected T1-2N1/T3N0-1 Supraglottic Cancer

Supraglottic tumors, like early-stage glottic malignancies, can be handled with either larynx-sparing surgery or RT monotherapy, with proven generally equivalent effectiveness. The main distinction between glottic and non-glottic tumors is the care of the neck due to the likelihood of nodal metastases.

Endoscopic resection or partial supraglottic laryngectomy are surgical techniques for T1-2 and low-volume T3 illness, with neck dissection being needed for T2 or T3 lesions. Many patients receive adjuvant RT for reasons such as positive nodal disease, extracapsular expansion, and positive margins. Definitive RT frequently includes at-risk cervical nodal sites, typically levels II to IV.

Locally Advanced Laryngeal Cancers

Locally advanced malignancies, such as T3-4N1-3 illness, are more difficult to treat and usually require a combination of therapies. These tumors, even if surgically resectable, are not amenable to laryngeal preservation surgery, while definitive radiotherapy combined with cisplatin chemotherapy remains an option for laryngeal preservation.

Unlike early-stage cancer, the treatment strategy to locally progressed disease is based on level I data, with combination chemotherapy and radiation displaying superior locoregional control and larynx preservation.

In the setting of T4 illness, laryngectomy and adjuvant RT have shown comparable locoregional control rates to chemoradiation and salvage surgery. Chemoradiation to preserve the larynx is not advised for T4 illness and is associated with a worse survival rate.

Post-operative RT is indicated in cases of emergent tracheostomy due to morbid tumor invasion (to reduce the risk of tumor spread into the tracheostomy), advanced tumor and nodal stage on surgical pathology, and other high-risk pathologic features such as close margins (less than 5 mm), perineural invasion, lymphovascular space invasion, and extracapsular extension. Furthermore, near or involved margins, many positive nodes, and extracapsular expansion need chemotherapy in addition to RT.

It is critical for the reader to understand that the innovative techniques of treating laryngeal cancer have not considerably improved survival rates but have instead reduced surgical morbidity.

Transoral laser microsurgery has recently gained popularity in the treatment of early glottic and supraglottic malignancies. However, surgical expertise is essential. The malignancy is removed piecemeal during surgery, and the margins are evaluated.

Post-operative RT /Chemoradiotherapy

In patients at high risk of locoregional recurrence, post-operative radiotherapy to the main site and/or neck can enhance locoregional control and survival. Post-operative RT is recommended for pT4 laryngeal cancers of any nodal stage, pT1/T2/T3 tumors with N2–N3 nodal stage, and all patients with close or positive resection margins and/or extracapsular spread; other unfavorable pathological factors, such as peri-neurial and vascular invasion, are relative indications for RT.

Concurrent cisplatin treatment with post-operative RT improves locoregional control and disease-free survival in locally advanced tumors compared to post-operative RT alone, but at the price of greater mucosal and haematological damage and probably higher mortality. This method increases overall survival in a subset of patients, notably those with extracapsular dissemination and/or positive margins, and should be reserved for patients who are at high risk of relapse.

Differential Diagnosis

• Acute sialadenitis
• Bacterial lymphadenopathy
• Benign tumours (rare)
• Branchial cleft cyst   
• Chronic laryngitis
• Chronic sialadenitis
• Contact granuloma
• Hemangioma
• HPV papillomas
• Laryngocele
• Polyps on the vocal cord(s)
• Reinke's edema
• Thyroglossal duct cyst

Staging

As with all head and neck malignancies, the initial diagnosis of laryngeal carcinoma is based on a thorough history and clinical examination in the clinic. Laryngeal malignancies are usually detectable in the outpatient department after a thorough examination of the larynx using a fiberoptic laryngoscope. Imaging is used to determine the stage of the tumor. While precise procedures vary depending on local imaging preferences, individuals suspected of having laryngeal cancer typically have magnetic resonance imaging (MRI) or computed tomography (CT) of the head and neck, as well as a CT scan of the thorax and upper abdomen.

The exception to this is when patients arrive with early stage T1 glottic lesions without anterior commissure involvement, in which case imaging is useless. Histological evaluation of a tissue biopsy collected during a general anaesthesia endoscopic examination of the larynx, pharynx, and upper oesophagus yields a definitive diagnosis. The inspection under anaesthesia is critical for staging.

The combined information supplied by imaging and endoscopic examination aids in tumor staging using the tumor–node–metastasis (TNM) paradigm detailed below. Treatment selections are finally decided based on the TNM stage of the tumor, as well as the patient's overall fitness.

Cancer may spread from where it began to other parts of the body.

Metastasis occurs when cancer spreads to another section of the body. Cancer cells break out from the original tumor and migrate via the lymph system or bloodstream.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The initial tumor and the metastatic tumor are both cancers. If laryngeal cancer spreads to the lung, the cancer cells in the lung are in fact laryngeal cancer cells. The condition is caused by metastatic laryngeal cancer, not lung cancer.

Conclusion 

An ENT surgeon, oncologist, nutritionist, pulmonologist, speech therapist, intensivist, and radiation therapist are part of an interprofessional team that treats laryngeal cancer. The majority of patients first report to the nurse practitioner or primary care physician with hoarseness, otalgia, dysphagia, and weight loss.

Patients are generally men who have a history of current or previous cigarette use. If the hoarseness persists and is linked with additional symptoms of cancer, an ENT surgeon should be consulted.

Because of the complexities of the treatment, an interprofessional approach comprising an ENT or oncologic surgeon, oncologist, speech therapist, respiratory therapist, and oncology nurses is recommended for assessment and follow-up therapy. To achieve the greatest results, the patient and family will need coordinated education on treatments and follow-up care.

The most important aspect of a physical examination is an invasive assessment of the main lesion, which may include indirect laryngoscopy, a mirror exam, and, in certain cases, fiberoptic endoscopy.

Surgery is used to treat laryngeal cancer, which is a technically hard and sophisticated procedure. Postoperative problems are prevalent, and patients' airway patency must be closely monitored. Early-stage laryngeal cancer has a decent prognosis, while advanced cancer has a poor prognosis.