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
Less common sites include the nasopharynx, nasal cavity and paranasal sinuses, hypopharynx, and salivary glands.
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) caused by human papillomavirus (HPV) infection. Head and neck cancer is more common among men than women at least in part because male smokers continue to outnumber female smokers and because oral HPV infection is more frequent in males.
Etiology
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 is associated with head and neck squamous cell carcinoma, particularly oropharyngeal cancer.
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.
Patients who in the past were treated with radiation for acne,
excess facial hair, enlarged thymus, or hypertrophic tonsils and
adenoids are predisposed to thyroid and salivary gland cancers and benign salivary tumors.
Epstein-Barr virus plays a role in the pathogenesis of nasopharyngeal cancer, and serum measures of certain Epstein-Barr virus proteins may be biomarkers of recurrence.
Symptoms and Signs
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
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Painful mucosal ulceration
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Visible mucosal lesion (eg, leukoplakia, erythroplakia)
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Hoarseness
Subsequent symptoms depend on location and extent of the tumor and include
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Pain
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Paresthesia
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Nerve palsies
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Trismus
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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
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Clinical evaluation
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Biopsy
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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. Any head and neck symptom (eg, sore throat, hoarseness,
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;
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
Head and neck cancers are staged according to size and site of
the primary tumor (T), number and size of metastases to the cervical
lymph nodes (N), and evidence of distant metastases (M) (1, 2). For oropharyngeal cancer, the HPV status also is taken into consideration. Staging usually requires imaging with CT, MRI, or both, and often PET.
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
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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.
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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
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
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Surgery, radiation therapy, or both
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Sometimes chemotherapy
The main treatments for head and neck cancer are surgery and radiation.
These modalities can be used alone or in combination and with or
without chemotherapy. Many tumors, regardless of location, respond
similarly to surgery and to radiation therapy, allowing other factors
such as patient preference or location-specific morbidity to determine
choice of therapy.
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, 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 pembrolizumab and nivolumab
are available for recurrent or metastatic disease resistant to platinum
based chemotherapy, but efficacy data so far are limited.
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, 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 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,
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 Systemic Disorders and the Mouth: Radiation therapy).
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.
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
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.
Current vaccines against HPV
target some of the HPV strains that cause oropharyngeal cancer, so
vaccination as currently recommended could be expected to lower the
incidence of these cancers.
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.
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