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Overview of Head and Neck Tumors


Bradley A. Schiff

, MD, Montefiore Medical Center, The University Hospital of Albert Einstein College of Medicine

Reviewed/Revised Dec 2022

Head and neck cancer develops in almost 65,000 people in the United States each year. Excluding skin and thyroid cancers, > 90% of head and neck cancers are squamous cell (epidermoid) carcinomas; most of the rest are adenocarcinomas, sarcomas, and lymphomas.

The most common sites of head and neck cancer are the

Other sites of head and neck tumors are

The incidence of head and neck cancer increases with age. Although most patients are between age 50 to 70 years, the incidence in younger patients is increasing, related to cancers (primarily oropharyngeal Oropharyngeal Squamous Cell Carcinoma Oropharyngeal cancer refers to cancer of the tonsil, base and posterior one third of the tongue, soft palate, and posterior and lateral pharyngeal walls. Squamous cell carcinoma comprises over... read more ) caused by human papillomavirus (HPV) infection Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more Human Papillomavirus (HPV) Infection . Head and neck cancer is more common among men than women at least in part because males who smoke continue to outnumber females who smoke and because oral HPV infection is more frequent in males.

Etiology of Head and Neck Tumors

The vast majority of patients, 85% or more, with cancer of the head and neck have a history of alcohol use, smoking, or both. Heavy long-term users of tobacco and alcohol have an almost 40-fold greater risk of developing squamous cell carcinoma. Other suspected causes include use of snuff or chewing tobacco, sunlight exposure, previous x-rays of the head and neck, certain viral infections, ill-fitting dental appliances, chronic candidiasis, and poor oral hygiene. In India, oral cancer is extremely common, probably because of chewing betel quid (a mixture of substances, also called paan). Long-term exposure to sunlight and the use of tobacco products are the primary causes of squamous cell carcinoma of the lower lip.

Human papillomavirus (HPV) infection Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more Human Papillomavirus (HPV) Infection is associated with head and neck squamous cell carcinoma, particularly oropharyngeal cancer Oropharyngeal Squamous Cell Carcinoma Oropharyngeal cancer refers to cancer of the tonsil, base and posterior one third of the tongue, soft palate, and posterior and lateral pharyngeal walls. Squamous cell carcinoma comprises over... read more . The increase in HPV-related cancer has caused an overall increase in the incidence of oropharyngeal cancer, which otherwise would have been expected to decrease because of the decrease in smoking over the last 2 decades or so. The mechanism for viral-mediated tumor genesis appears to be distinct from tobacco-related pathways.

Symptoms and Signs of Head and Neck Tumors

The manifestations of head and neck cancer depend greatly on the location and extent of the tumor. Common initial manifestations of head and neck cancers include

Subsequent symptoms depend on location and extent of the tumor and include

  • Pain

  • Paresthesia

  • Nerve palsies

  • Trismus

  • Halitosis

Otalgia is an often overlooked symptom usually representing referred pain from the primary tumor. Weight loss caused by perturbed eating and odynophagia is also common.

Diagnosis of Head and Neck Tumors

  • Clinical evaluation

  • Biopsy

  • Imaging tests and endoscopy to evaluate extent of disease

Routine physical examination (including a thorough oral examination) is the best way to detect cancers early before they become symptomatic. Commercially available brush biopsy kits help screen for oral cancers. Unexplained head and neck symptoms such as sore throat, hoarseness, or otalgia lasting > 2 to 3 weeks should prompt referral to a head and neck specialist who will typically do flexible fiberoptic laryngoscopy to evaluate the larynx and pharynx.

Definitive diagnosis usually requires a biopsy. Fine-needle aspiration is used for a neck mass Neck Mass Patients or their family members may notice a mass in the neck, or a mass may be discovered during routine examination. A neck mass may be painless or painful depending on the cause. When a... read more ; it is well tolerated, accurate, and, unlike an open biopsy, does not impact future treatment options. Oral lesions are evaluated with an incisional biopsy or a brush biopsy. Nasopharyngeal, oropharyngeal, or laryngeal lesions are biopsied endoscopically.

Imaging (CT, MRI, or PET/CT) is done to help determine the extent of the primary tumor, involvement of adjacent structures, and spread to cervical lymph nodes.

Staging of Head and Neck Tumors

Clinical staging (cTNM) is based on the results of the physical examination and tests done before surgery. Pathologic staging (pTNM) is based on the pathologic characteristics of the primary tumor and the number of positive nodes found during surgery.

Extranodal extension is incorporated into the "N" category for metastatic cancer to neck nodes. Clinical diagnosis of extranodal extension is based on finding evidence of gross extranodal extension during the physical examination together with imaging tests confirming the finding. Pathologic extranodal extension is defined as histologic evidence of tumor in a lymph node extending through the lymph node capsule into the surrounding connective tissue, with or without associated stromal reaction.

Staging references

  • 1. Amin MB, Edge S, Greene F, Byrd DR, et al: American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. New York, Springer, 2017; AJCC Cancer Staging Form Supplement, 2018.

  • 2. Cramer JD, Reddy A, Ferris RL, et al: Comparison of the seventh and eighth edition American Joint Committee on Cancer oral cavity staging systems. Laryngoscope, 128(10):2351-2360, 2018. doi: 10.1002/lary.27205

Prognosis for Head and Neck Tumors

Prognosis in head and neck cancer varies greatly depending on the tumor size, primary site, etiology, and presence of regional or distant metastases. In general, the prognosis is favorable if diagnosis is early and treatment is timely and appropriate.

Head and neck cancers first invade locally and then metastasize to regional cervical lymph nodes. The spread to regional lymphatics is partially related to tumor size, extent, and aggressiveness and reduces overall survival by nearly half. Distant metastases (most often to the lungs) tend to occur later, usually in patients with advanced-stage disease. Distant metastases greatly reduce survival and are almost always incurable.

Advanced local disease (a criterion for advanced T stage) with invasion of muscle, bone, or cartilage also significantly decreases cure rate. Perineural spread, as evidenced by pain, paralysis, or numbness, indicates a highly aggressive tumor, is associated with nodal metastasis, and has a less favorable prognosis than a similar lesion without perineural invasion.

With appropriate treatment, 5-year survival can be as high as 90% for stage I, 75 to 80% for stage II, 45 to 75% for stage III, and up to 50% for some stage IV cancers. The survival rates vary greatly depending on the primary site and etiology. Stage I laryngeal cancers have an excellent survival rate when compared to other sites. Oropharyngeal cancers caused by HPV have a significantly better prognosis compared with oropharyngeal tumors caused by tobacco or alcohol. Because the prognosis between HPV-positive and HPV-negative oropharyngeal cancers differs, all tumors of the oropharynx should be routinely tested for HPV.

Treatment of Head and Neck Tumors

  • Surgery, radiation therapy, or both

  • Sometimes chemotherapy

However, at certain locations, there is clear superiority of one modality. For example, surgery is better for early-stage disease involving the oral cavity because radiation therapy has the potential to cause mandibular osteoradionecrosis. Endoscopic surgery has become more frequently used; in select head and neck cancers, it has cure rates similar to or better than those of open surgery or radiation, and its morbidity is significantly less. Endoscopic approaches are most often used for laryngeal surgery and usually use a laser to make the cuts. Endoscopic approaches also are being used in the treatment of selected sinonasal tumors.

If radiation therapy is chosen for primary therapy, it is delivered to the primary site and sometimes bilaterally to the cervical lymph nodes. The treatment of lymphatics, whether by radiation or surgery, is determined by the primary site, histologic criteria, and risk of nodal disease. Early-stage lesions often do not require treatment of the lymph nodes, whereas more advanced lesions do. Head and neck sites rich in lymphatics (eg, oropharynx, supraglottis) usually require lymph node radiation regardless of tumor stage, whereas sites with fewer lymphatics (eg, larynx) usually do not require lymphatic radiation for early-stage disease. Intensity-modulated radiation therapy (IMRT) delivers radiation to a very specific area, potentially reducing adverse effects without compromising tumor control.

Advanced-stage disease (stages III and IV) often requires multimodality treatment, incorporating some combination of chemotherapy, radiation therapy, and surgery. Bone or cartilage invasion requires surgical resection of the primary site and usually regional lymph nodes because of the high risk of nodal spread. If the primary site is treated surgically, then postoperative radiation to the cervical lymph nodes is delivered if there are high-risk features, such as multiple lymph nodes with cancer or extracapsular extension. Postoperative radiation usually is preferred over preoperative radiation because radiated tissues heal poorly.

Recent studies have shown that adding chemotherapy to adjuvant radiation therapy to the neck improves regional control of the cancer and improves survival. However, this approach causes significant adverse effects, such as increased dysphagia and bone marrow suppression, so the decision to add chemotherapy should be carefully considered.

Advanced squamous cell carcinoma without bony invasion often is treated with concomitant chemotherapy and radiation therapy. Although advocated as organ-sparing, combining chemotherapy with radiation therapy doubles the rate of acute toxicities, particularly severe dysphagia. Radiation may be used alone for debilitated patients with advanced disease who cannot tolerate the sequelae of chemotherapy and are too high a risk for general anesthesia.

Chemotherapy is almost never used as primary treatment for cure. Primary chemotherapy is reserved for chemosensitive tumors, such as Burkitt lymphoma Burkitt Lymphoma Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma occurring in children and adults. Endemic (African), sporadic (non-African), and immunodeficiency-related forms exist. (See also... read more Burkitt Lymphoma , or for patients who have widespread metastases (eg, hepatic or pulmonary involvement). Several drugs—cisplatin, fluorouracil, bleomycin, and methotrexate—provide palliation for pain and shrink the tumor in patients who cannot be treated with other methods. Response may be good initially but is not durable, and the cancer almost always returns. Targeted drugs such as cetuximab are increasingly used instead of traditional chemotherapy drugs for select patients, but efficacy data so far are limited.

Because the treatment of head and neck cancer is so complex, multidisciplinary treatment planning is essential. Ideally, each patient should be discussed by a tumor board consisting of members of all treating disciplines, along with radiologists and pathologists, so that a consensus can be reached on the best treatment. Once treatment has been determined, it is best coordinated by a team that includes ear, nose, and throat and reconstructive surgeons, radiation and medical oncologists, speech and language pathologists, dentists, and nutritionists.

Plastic and reconstructive surgeons play an increasingly important role because the use of free-tissue transfer flaps has allowed functional and cosmetic reconstruction of defects to significantly improve a patient's quality of life after procedures that previously caused excessive morbidity have been done. Common donor sites used for reconstruction include the fibula (often used to reconstruct the mandible), the radial forearm (commonly used for the tongue and floor of mouth), and the anterior lateral thigh (often used for laryngeal or pharyngeal reconstruction).

Treatment of tumor recurrence

Managing recurrent tumors after therapy is complex and has potential complications. A palpable mass or ulcerated lesion with edema or pain at the primary site after therapy strongly suggests a persistent tumor. Such patients require CT (with thin cuts) or MRI.

For local recurrence after surgical treatment, all scar planes and reconstructive flaps are excised along with residual cancer. Radiation therapy, chemotherapy, or both may be done but have limited effectiveness. Patients with recurrence after radiation therapy are best treated with surgery. However, some patients may benefit from additional radiation treatments, but this approach has a high risk of adverse effects and should be done with care. The immune checkpoint inhibitors Immunotherapy and Targeting Inhibitors of Immune Responses A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more pembrolizumab and nivolumab are available for recurrent or metastatic disease resistant to platinum based chemotherapy; while the early results are promising, best practices for integrating these treatments into clinical care are not yet clear.

Symptom control

Pain is a common symptom in patients with head and neck cancer and must be adequately addressed. Palliative surgery or radiation may temporarily alleviate pain, and in 30 to 50% of patients, chemotherapy can produce improvement that lasts a mean of 3 months. A stepwise approach to pain management, as recommended by the World Health Organization: Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents, is critical to controlling pain. Severe pain is best managed in association with a pain and palliative care specialist.

Pain, difficulty eating, choking on secretions, and other problems make adequate symptomatic treatment essential. Patient advance directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more regarding such care should be clarified early.

Adverse effects of treatment

All cancer treatments have potential complications and expected sequelae. Because many treatments have similar cure rates, the choice of modality is based largely on real, or perceived, differences in sequelae.

Although it is commonly thought that surgery causes the most morbidity, many procedures can be done without significantly impairing appearance or function. Increasingly complex reconstructive procedures and techniques, including prostheses, grafts, regional pedicle flaps, and complex free flaps, can restore function and appearance often to near normal.

Toxic effects of chemotherapy include malaise, severe nausea and vomiting, mucositis, transient hair loss, gastroenteritis, hematopoietic and immune suppression, and infection.

Therapeutic radiation for head and neck cancers has several adverse effects. The function of any salivary gland within the beam is permanently destroyed by a dose of about 40 Gray, resulting in xerostomia Xerostomia Xerostomia is dry mouth caused by reduced or absent flow of saliva. This condition can result in discomfort, interfere with speech and swallowing, make wearing dentures difficult, cause halitosis... read more , which markedly increases the risk of dental caries. Newer radiation techniques, such as intensity-modulated radiation therapy (IMRT), can minimize or eliminate toxic doses to the parotid glands in certain patients.

In addition, the blood supply of bone, particularly in the mandible, is compromised by doses of > 60 Gray, and osteoradionecrosis may occur (see also Radiation Therapy Radiation therapy Clues suggesting systemic disease may be found in the mouth and adjacent structures (see Introduction to the Approach to the Dental Patient and table Oral Findings in Systemic Disorders). A... read more ). In this condition, tooth extraction sites break down, sloughing bone and soft tissue. Therefore, any needed dental treatment, including scaling, fillings, and extractions, should be done before radiation therapy. Any teeth in poor condition that cannot be rehabilitated should be extracted. It is unclear whether hyperbaric oxygen therapy Recompression Therapy Recompression therapy is administration of 100% oxygen for up to several hours in a sealed chamber pressurized to at least 1.9 (usually 1.9 to 3.0) atmospheres, gradually lowered to atmospheric... read more can hep prevent osteoradionecrosis after dental extraction.

Radiation therapy may also cause oral mucositis and dermatitis in the overlying skin, which may result in dermal fibrosis. Loss of taste (ageusia) and impaired smell (dysosmia) often occur but are usually transient.

Prevention of Head and Neck Tumors

Removing risk factors is critical, and all patients should cease tobacco use and limit alcohol consumption. Removing risk factors also helps prevent disease recurrence in patients treated for cancer. A new primary cancer develops in about 5% of patients/year (to a maximum risk of about 20%); risk is lower in those who stop using tobacco.

Cancer of the lower lip may be prevented by sunscreen use and tobacco cessation. Because 60% of head and neck cancers are well advanced (stage III or IV) at the time of diagnosis, the most promising strategy for reducing morbidity and mortality is diligent routine examination of the oral cavity.

Drugs Mentioned In This Article

Drug Name Select Trade
Platinol, Platinol -AQ
Adrucil, Carac, Efudex, Fluoroplex, Tolak
Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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