Squamous Cell Carcinoma of Head and Neck

Head and neck squamous cell carcinoma, HNSCC, SCCHN

Squamous cell carcinoma of the head and neck is a cancer that develops in the moist tissues lining your mouth, nose, and throat, with most cases linked to tobacco use, heavy alcohol consumption, or infection with human papillomavirus (HPV).

Table of contents

• What is squamous cell carcinoma of head and neck
• Where the cancer develops
• How common is this cancer
• What causes this cancer
• Signs and symptoms
• How doctors diagnose this cancer
• Treatment options
• Outlook and survival
• Reducing your risk

What is squamous cell carcinoma of head and neck

Squamous cell carcinoma of the head and neck, often called HNSCC, is a type of cancer that arises from special cells called squamous cells. These are thin, flat cells found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and digestive system^[3]. In head and neck cancer, these cells are found in the mucosal surfaces of the mouth, nose, and throat^[2].

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx, and larynx, and are known collectively as head and neck squamous cell carcinoma^[4]. These cancers usually begin in the squamous cells that line the mucosal surfaces of the head and neck, such as those inside the mouth, throat, and voice box^[2].

Where the cancer develops

• Oral cavity (lips, tongue, gums, inside of cheeks and lips, floor of mouth, hard palate)
• Pharynx (throat, including nasopharynx, oropharynx, and hypopharynx)
• Larynx (voice box)
• Nasal cavity and paranasal sinuses
• Salivary glands

Head and neck cancers can form in several specific areas. The oral cavity includes the lips, the front two-thirds of the tongue, the gums, the lining inside the cheeks and lips, the floor of the mouth under the tongue, the hard palate (bony top of the mouth), and the small area of the gum behind the wisdom teeth^[2].

The throat (pharynx) is a hollow tube about 5 inches long that starts behind the nose and leads to the esophagus. It has three parts: the nasopharynx (the upper part of the pharynx, behind the nose); the oropharynx (the middle part of the pharynx, including the soft palate, the base of the tongue, and the tonsils); and the hypopharynx (the lower part of the pharynx)^[2].

The voice box (larynx) is a short passageway formed by cartilage just below the pharynx in the neck. The voice box contains the vocal cords. It also has a small piece of tissue, called the epiglottis, which moves to cover the voice box to prevent food from entering the air passages^[2].

Other areas include the paranasal sinuses, which are small hollow spaces in the bones of the head surrounding the nose, and the nasal cavity, which is the hollow space inside the nose. The major salivary glands are in the floor of the mouth and near the jawbone, producing saliva^[2].

How common is this cancer

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide. Approximately 600,000 new cases are diagnosed each year, including about 50,000 in the United States^[3]. About 4.5% of cancer diagnoses worldwide are head and neck cancers^[14].

HNSCC occurs most often in men in their 50s or 60s, although the incidence among younger individuals is increasing^[3]. Most head and neck cancers affect males over 50, but this may be because this group is more likely to have risk factors associated with these cancers, like a history of tobacco use^[14].

In the United States, instances of tobacco-related head and neck cancers have fallen. Head and neck cancers related to HPV (a type of sexually transmitted infection) are on the rise. Alongside this shift, more people getting diagnosed are under 50^[14].

What causes this cancer

Squamous cell carcinoma of the head and neck can be separated into two main types based on what causes them: HPV-negative HNSCC and HPV-positive HNSCC^[4].

Alcohol and tobacco use (including secondhand smoke and smokeless tobacco, sometimes called “chewing tobacco” or “snuff”) are the two most important risk factors for head and neck cancers, especially cancers of the oral cavity, hypopharynx, and voice box^[2]. People who use both tobacco and alcohol are at greater risk of developing these cancers than people who use either tobacco or alcohol alone^[2]. Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse, or both^[4].

Infection with certain strains of human papillomavirus (HPV) is linked to the development of HNSCC. HPV infection accounts for the increasing incidence of HNSCC in younger people^[3]. Pharynx cancers are increasingly attributed to infection with human papillomavirus, primarily HPV-16^[4]. In particular, HPV infection is a risk factor for oropharyngeal cancer (cancer of the middle of the throat, including the tonsils and base of tongue)^[12].

The overall incidence of HPV-positive head and neck cancers is rapidly increasing in the United States, while the incidence of HPV-negative (primarily tobacco- and alcohol-related) cancer is decreasing. HPV-related head and neck cancer has a unique risk factor profile, and a more favorable prognosis than tobacco or alcohol induced HNSCC^[12].

Researchers have identified mutations in many genes in people with HNSCC. The proteins produced from several of the genes associated with HNSCC, including TP53, NOTCH1, and CDKN2A, function as tumor suppressors, which means they normally keep cells from growing and dividing too rapidly or in an uncontrolled way. When tumor suppressors are impaired, cells can grow and divide without control, leading to tumor formation. It is likely that a series of changes in multiple genes is involved in the development and progression of HNSCC^[3].

Signs and symptoms

Head and neck cancer symptoms are often mild. They can mimic less serious conditions like a cold or sore throat. A sore throat that doesn’t get better is the most common sign of head and neck cancer^[14].

HNSCC can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes^[3].

Depending on the type of head and neck cancer, you may experience a persistent sore throat, persistent earaches or symptoms of ear infections (especially when your ear looks normal to your healthcare provider), frequent headaches, pain in your face or neck that won’t go away, pain in your upper teeth, pain when you chew or swallow, hoarseness or voice changes, or trouble breathing or speaking^[14].

You may notice a lump in your throat, mouth or neck, a mouth or tongue sore that doesn’t heal, frequent nosebleeds or bloody saliva or phlegm, a white or red patch on your gums, tongue or inside your mouth, or swelling in your jaw, neck or side of your face (that may cause your dentures to fit poorly)^[14].

How doctors diagnose this cancer

Head and neck cancer diagnosis often begins with an exam of the head and neck area. Other tests might include imaging tests and a procedure to remove some cells for testing. The tests used for diagnosis may depend on the cancer’s location^[13].

A healthcare professional may look at your head and neck area for sores or other issues. The health professional might feel your neck for lumps or swelling. To see inside your mouth, the health professional might use a light and a mirror. To see inside the throat, sometimes a tiny camera is put down the throat. The camera transmits images that let the health professional look for signs of cancer. To see inside the nose, a tiny camera can go through the nostrils^[13].

Imaging tests make pictures of the inside of the body. The pictures can show the size and location of the cancer. Imaging tests used for head and neck cancer include CT, MRI, and positron emission tomography scans, also called PET scans^[13].

A biopsy is a procedure to remove a sample of tissue for testing in a lab. How the cells are collected depends on the cancer’s location. If the cancer is easy to access, a healthcare professional might cut out some of the tissue with a cutting tool. Sometimes a needle can go through the skin and into the cancer to draw out some cells. Special tools can collect cells from inside the throat or inside the nose^[13].

The tissue sample collected during a biopsy goes to a lab for testing. Tests can show if the cells are cancerous. Other special tests give more details about the cancer cells, which helps determine treatment options^[13].

Treatment options

Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers^[4]. The treatment approach is generally multimodal, consisting of surgery followed by chemotherapy plus radiation (chemoradiation or CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers^[4].

Treatment for head and neck cancer depends on individual factors, including the exact location of the tumor, stage of the tumor, and a person’s general health. These conventional treatments for head and neck cancer (surgery, radiation, and chemotherapy) may be used alone or in combination, depending on stage and location^[5].

Head and neck cancer is highly curable—often with single-modality therapy (surgery or radiation)—if detected early. More advanced head and neck cancers are generally treated with various combinations of surgery, radiation, and chemotherapy. With any treatment plan, the goal is not only to remove the cancer, but also to preserve the functions of the structures involved in speaking, swallowing, and expression^[12].

The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy^[4]. Cetuximab (Erbitux) is a monoclonal antibody that targets the EGFR pathway and is approved for subsets of patients with advanced head and neck cancer, including as a first-line therapy^[12].

The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease^[4]. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are checkpoint inhibitors that target the PD-1/PD-L1 pathway and are approved for subsets of patients with advanced head and neck cancer^[12].

If head and neck cancer is going to spread, it almost always does so locally and/or to the lymph nodes in the neck^[2]. If it spreads, the cancer has a worse prognosis and can be fatal^[3].

Outlook and survival

About half of affected individuals survive more than five years after diagnosis^[3]. The five-year survival rate of patients with head and neck cancer is about 60 percent^[12].

Despite significant investment in research to investigate different treatment regimens for head and neck cancer, limited improvement in patient survival has been achieved in the last 30 years in many countries. One reason for this is that head and neck cancer is frequently diagnosed at an advanced stage^[17].

Most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion, despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC^[4].

Reducing your risk

HNSCC is generally not inherited; it typically arises from mutations in the body’s cells that occur during an individual’s lifetime. This type of alteration is called a somatic mutation^[3]. You can reduce your risk by avoiding tobacco, limiting alcohol, and getting the HPV vaccine. These cancers are often treatable if caught early, and most are preventable^[14].

The strongest risk factors for developing this form of cancer are tobacco use (including smoking or using chewing tobacco) and heavy alcohol consumption^[3]. Environmental risk factors for head and neck cancers include tobacco use, heavy alcohol consumption, prolonged sun exposure, and certain viruses, including human papilloma virus (HPV) and Epstein-Barr virus (EBV)^[12].

One HPV vaccine, Gardasil-9, is approved for the prevention of infection by HPV types 16, 18, 31, 33, 45, 52, and 58, and for the prevention of genital warts caused by HPV types 6 or 11. This vaccine can help prevent the development of HPV-related head and neck cancers^[12].