Overview of the diagnosis and staging of head and neck cancer

Authors
Colin S Poon, MD, PhD, FRCPC
Kerstin M Stenson, MD, FACS
Section Editors
Bruce E Brockstein, MD
Marvin P Fried, MD, FACS
Deputy Editor
Michael E Ross, MD
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Mar 2015. &#124 This topic last updated: Mar 09, 2015.

INTRODUCTION — Head and neck cancers can arise in the oral cavity, pharynx, larynx, nasal cavity,
paranasal sinuses, thyroid, and salivary glands and include a variety of histopathologic tumors.

An overview of the epidemiology, clinical presentation, diagnosis, and staging for head and neck
cancer is presented here. More detailed discussions for specific primary tumor site are presented
in the relevant site-specific topics. A general overview of treatment is also presented separately.
(See "Overview of treatment for head and neck cancer".)

EPIDEMIOLOGY AND RISK FACTORS — There are large geographic differences in the incidence and
primary site of head and neck cancers. These likely reflect the prevalence of risk factors, such as
tobacco and alcohol consumption, as well as ethnic and genetic differences among populations.

Although the highest rates of head and neck cancer are in older males, the incidence has been
increasing in females as more women use tobacco, and in young non-smokers as human
papillomavirus (HPV) plays an increasingly prominent role as an etiologic factor in the
development of oropharyngeal head and neck cancer.

Tobacco (smoked and smokeless) is the most important known risk factor for the development of
head and neck cancer. There is some evidence for a genetic predisposition to the carcinogenic
effects of tobacco. In addition, tobacco and alcohol consumption appear to have a synergistic
effect. The repeated exposure of the mucosa of the upper aerodigestive tract to the carcinogenic
effects of tobacco, alcohol, or both appears to cause multiple primary and secondary tumors in
this “condemned mucosa”, a phenomenon described as "field cancerization".

HPV infection is a causative agent for head and neck cancer. HPV-associated head and neck
cancers occur primarily in the oropharynx (tonsils and base of tongue), account for the younger
age of patients with oropharyngeal squamous cell carcinoma, and define a subset of patients with
improved treatment outcome. However, the use of HPV status in clinical decision making remains
investigational at this time, and treatment is the same as for patients without an HPV-associated
tumor. (See "Human papillomavirus associated head and neck cancer".)

Other head and neck cancer risk factors include betel nut chewing, radiation exposure, vitamin
deficiencies, periodontal disease, immunosuppression, and other environmental and occupational
exposures. (See "Epidemiology and risk factors for head and neck cancer" and "Second primary
malignancies in patients with head and neck cancers".)
ANATOMIC SUBSITES — Head and neck cancer encompasses a variety of cancers, mostly
squamous cell carcinoma, arising from a variety of sites. The head and neck region consists of
several anatomic areas (figure 1):

●The oral cavity includes the lips, buccal mucosa, anterior tongue, floor of the mouth, hard palate,
and upper and lower gingiva. The anterior border of the oral cavity is defined by the vermillion of
the lips. The posterior border is defined by the circumvallate papillae of the tongue, the anterior
tonsillar pillars (palatoglossus muscles), and the posterior margin of the hard palate. The hard
palate defines the superior boundary of the oral cavity. Inferiorly, the oral cavity is defined by the
mylohyoid muscles. The lateral boundary of the oral cavity is defined by the buccomasseteric
region (buccal mucosa of the cheeks) and the retromolar trigone (which is located behind the
mandibular third molar).

●The pharynx is divided into the nasopharynx, oropharynx, and hypopharynx.

•The nasopharynx forms the continuation of the nasal cavity. The boundary between the nasal
cavity and nasopharynx is defined by the posterior choanae of the nasal cavity. The nasopharynx is
defined superiorly by the basisphenoid and basiocciput (clivus) and inferiorly by the hard and soft
palate. The prevertebral muscle and anterior margin of the cervical spine at C1 and C2 levels form
the posterior margin of the nasopharynx. The posterolateral boundary of the nasopharynx
includes several important structures. The lateral wall of the nasopharynx is elevated by the torus
tubarius, a cartilaginous structure that constitutes the opening of the Eustachian tube. The
Eustachian tube allows communication between the middle ear and the nasopharynx through a
defect (sinus of Morgagni) of the pharyngobasilar fascia, which lines the nasopharynx. The sinus of
Morgagni may allow nasopharyngeal cancer to gain access into the skull base. The fossa of
Rosenmuller (lateral nasopharyngeal recess), a common site of nasopharyngeal cancer, is located
posterior to the torus tubarius. The nasopharynx also includes the adenoids (nasopharyngeal
tonsils), located in the midline roof of the nasopharynx.

•The soft palate defines the boundary between the nasopharynx and oropharynx. The oropharynx
is separated anteriorly from the oral cavity by the circumvallate papillae and the anterior tonsillar
pillars. The palatine tonsils, posterior tonsillar pillars, tongue base (posterior one-third of the
tongue), valleculae, soft palate and the posterior pharyngeal wall are structures of the oropharynx.
Inferiorly, the oropharynx is defined by the hyoid and the pharyngoepiglottic folds.

•The hypopharynx includes the pyriform sinuses, the posterior surface of the larynx (postcricoid
area), and the inferior, posterior, and lateral pharyngeal walls.

●The larynx, which is divided into three anatomic regions: the supraglottic region, the glottic
larynx (true vocal cords and mucosa of the anterior and posterior commissures), and the subglottic
larynx, which extends to the inferior border of the cricoid cartilage.

●The nasal cavity and the paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal).

●The major (parotid, submandibular, and sublingual) and minor salivary glands. Minor salivary
glands are found within the submucosa throughout the oral cavity, palate, paranasal sinuses,
pharynx, larynx, trachea and bronchi, but are most concentrated in the buccal, labial, palatal, and
lingual regions.
CLINICAL PRESENTATION — The clinical presentation of head and neck cancer varies widely
depending upon the primary site and exposure to various risk factors.

●Nasopharyngeal carcinoma – The most frequent presenting complaint is a neck mass due to
regional lymph node metastasis, which occurs in nearly 90 percent of patients. Symptoms due to
the primary tumor may include hearing loss (associated with serous otitis media), tinnitus, nasal
obstruction and pain, and its associated growth into adjacent anatomical structures, which can
lead to muscle involvement and impaired function of cranial nerves II to VI.

●Oral cavity tumors – Patients may present with mouth pain or nonhealing mouth ulcers,
loosening of teeth, ill-fitting dentures, dysphagia, odynophagia, weight loss, bleeding, or referred
otalgia. Up to 66 percent of patients with primary tongue lesions have cervical lymph node
involvement, depending on T-stage and depth of invasion, while the incidence is substantially
lower in patients with hard palate cancers.

•Tongue cancer may grow as an infiltrative and/or exophytic lesion. The presenting symptom is

often pain, with or without dysarthria. Dysarthria implies deep muscle invasion of advanced tumor
stage. There may be a history of longstanding leukoplakia or erythroplakia.

•Lip cancer usually presents as an exophytic or ulcerative lesion of the lower lip, occasionally
associated with bleeding or pain. Some patients complain of numbness of the skin of the chin due
to involvement of the mental nerve.

●Oropharyngeal tumors – Presenting complaints can include dysphagia, pain (odynophagia,

otalgia), obstructive sleep apnea or snoring bleeding, or a neck mass.

Patients with HPV positive oropharyngeal cancers often present with cystic neck masses. These
cystic neck masses are often mistaken for branchial cleft cyst carcinomas. In reality, branchial cleft
cyst carcinoma is exceptionally rare and its diagnosis should be one of exclusion rather than
presumption [1]. For adult patients presenting with cystic neck mass, metastatic cystic squamous
cell carcinoma associated with HPV needs to be strongly considered and excluded. (See "Human
papillomavirus associated head and neck cancer".)

●Hypopharyngeal tumors –  Patients with these tumors often remain asymptomatic for a longer
period and are therefore more likely to be seen in the later stages of the disease. Dysphagia,
odynophagia, otalgia, weight loss, hemoptysis, dyspnea, and neck mass are common presenting
symptoms.

•Significance of otalgia: Cranial nerves 5, 7, 9, and 10 contribute afferents to the external and
middle ear. Referred otalgia is considered a “red flag” in the evaluation of a patient with a possible
head and neck malignancy

●Laryngeal cancer – The symptoms associated with cancer of the larynx depend upon location.
Persistent hoarseness may be the initial complaint in glottic cancers; later symptoms may include
dysphagia, referred otalgia, chronic cough, hemoptysis, and stridor. Supraglottic cancers are often
discovered later and may present with airway obstruction or palpable metastatic lymph nodes.
Primary subglottic tumors are rare. Affected patients typically present with stridor or complaints of
dyspnea on exertion.

●Sinus tumors – Common presenting symptoms of sinus tumors include epistaxis and unilateral
nasal obstruction. Facial and/or head pain may be seen in later stages, due to pressure or tumor
infiltration into nerves or periosteum.

PATHOLOGY — Squamous cell carcinomas account for 90 to 95 percent of the lesions in the oral
cavity and larynx. They can be categorized as well differentiated (greater than 75 percent
keratinization), moderately differentiated (25 to 75 percent keratinization), and poorly
differentiated (less than 25 percent keratinization) tumors. Less common histologies include
verrucous carcinoma (a variant of squamous cell carcinoma), adenocarcinoma, adenoid cystic
carcinoma, and mucoepidermoid carcinomas. (See "Pathology of head and neck neoplasms",
section on 'Squamous cell carcinoma'.)

Squamous cell carcinoma of the head and neck cancer often develops through a series of changes
from premalignant entities. (See "Pathology of head and neck neoplasms", section on 'Squamous
cell cancer precursors'.)

●Clinical signs

•Leukoplakia is characterized by hyperparakeratosis and is usually associated with underlying

epithelial hyperplasia. In the absence of underlying dysplastic changes, the probability of
malignant change is less than 5 percent [2].

•Erythroplakia is characterized by red superficial patches adjacent to normal mucosa. It is

commonly associated with epithelial dysplasia and is associated with carcinoma in situ or invasive
tumor in up to 40 percent of cases [2].

●Histopathologic findings

•Dysplasia is characterized histopathologically by the presence of mitoses and prominent nucleoli.

Involvement of the entire mucosal thickness is usually referred to as carcinoma in situ. Dysplasia is
associated with progression to invasive cancer in 15 to 30 percent of cases.

TNM STAGING SYSTEM — The tumor node metastases (TNM) staging system of the American Joint
Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC) is used to
classify cancers of the head and neck [3]. The T classifications indicate the extent of the primary
tumor and are site specific; there is considerable overlap in the cervical node (N) classifications.

TNM staging varies depending upon the primary tumor site:

●Oral cavity (table 1) (see "Treatment of early (stage I and II) head and neck cancer: The oral
cavity", section on 'Anatomy and staging')

●Nasopharynx (table 2) (see "Treatment of early and locoregionally advanced nasopharyngeal

carcinoma", section on 'Staging and pathology')
●Oropharynx (table 3) (see "Treatment of early (stage I and II) head and neck cancer: The
oropharynx", section on 'Staging')

●Hypopharynx (table 4) (see "Treatment of early (stage I and II) head and neck cancer: The
hypopharynx", section on 'Anatomy and staging')

●Larynx (table 5) (see "Treatment of early (stage I and II) head and neck cancer: The larynx",
section on 'Staging and anatomy')

●Nasal cavity and paranasal sinuses (table 6) (see "Cancer of the nasal vestibule", section on
'Staging' and "Paranasal sinus cancer", section on 'Diagnosis and staging' and "Tumors of the nasal
cavity")

●Salivary glands (table 7) (see "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and
staging", section on 'Staging')

DIAGNOSIS AND STAGING EVALUATION

Initial evaluation — The initial assessment of the primary tumor is based upon a thorough history
and combination of inspection, palpation, indirect mirror examination, or direct flexible
laryngoscopy. Physical examination should include careful assessment of the nasal cavity and oral
cavity with visual examination and/or palpation of mucous membranes, the floor of the mouth,
the anterior two-thirds of the tongue, tonsillar fossae and tongue base (best seen on mirror
examination or flexible laryngoscopy), palate, buccal and gingival mucosa, and posterior
pharyngeal wall.

External auditory canal examination and anterior rhinoscopy should be undertaken.

For patients with non-laryngeal lesions but a strong alcohol or smoking history, flexible
laryngoscopy is commonly undertaken to visualize potential other lesions and to document vocal
cord mobility.

A metastatic work-up with appropriate imaging is recommended for all newly-diagnosed head and
neck cancer patients, with particular attention to regional lymph node spread. For those with
locoregionally advanced tumors, distant metastatic imaging, with attention to the lungs, is often
performed. Patients with severe dysplasia or carcinoma in-situ who have a strong smoking,
alcohol, or family history of cancer may also benefit from a more extensive work-up for
metastases or a second primary. Use of clinical judgement is important.

Visualization of lesions outside the mouth is best accomplished by mirror examination and/or the

use of a flexible fiberoptic endoscope with the goal of examining all of the mucosa in the
nasopharynx oropharynx, hypopharynx, and larynx. Aside from mucosal irregularities, other
abnormalities that should be specifically searched for are impairment of vocal cord mobility,
pooling of secretions, asymmetries, and bleeding. The appropriate nodal drainage areas are
examined by careful palpation of the neck. Examination of the neck for pathologic adenopathy or
other masses is best done according to neck levels. The parotid glands are also palpated for
abnormalities (figure 2).
An examination under anesthesia often is performed to best characterize the extent of the tumor,
to look for synchronous second primary tumors, and to take biopsies for a tissue diagnosis. This
exam is particularly useful for patients with laryngeal and hypopharyngeal malignancies.
Symptom-directed panendoscopy (laryngoscopy, bronchoscopy and esophagoscopy) reveals a 2.4
to 4.5 percent incidence of second primary tumors of the upper aerodigestive tract, but not of the
lower airways [4-6]. Other authors have found that screening panendoscopy revealed second
primary cancers only in patients with a current or past smoking history [7]. There is evidence that
positron emission tomography (PET) may complement or replace panendoscopy in detecting
synchronous primary cancers [8], although some studies have shown there is still a risk of false
negatives (9 in 589 patients in one study). In general, patients with a history of heavy alcohol or
tobacco use should undergo a work-up for second primary tumors with PET or panendoscopy as
part of their operative staging for characterization of the primary tumor or to look for distant
disease in early stage disease. Operative stagingand/or panendoscopy may find synchronous
primaries that are too small to be identified with PET, while PET may identify lower aerodigestive
tract tumors not seen with panendoscopy. Although the incidence of second or synchronous
primary tumor is low, the impact on treatment for the individual patient is significant. Those with
HPV positive tumors without other known risk factors are not as likely to benefit from
panendoscopy.

Imaging studies may augment the physical exam and evaluation of squamous cell carcinoma of the
head and neck, particularly for assessing the degree of local invasion, involvement of regional
lymph nodes, and presence of distant metastases or second primary malignancies. The most
common metastatic sites are the lungs, liver, and bone, while the most common sites of second
primary malignancies are the head and neck, followed by the lungs and esophagus. Ideally,
imaging should take place prior to biopsy, which may distort anatomy and create a false positive
finding on PET scanning. (See 'Imaging studies' below and 'Evaluation for distant metastases'
below.)

Fine needle aspiration biopsy — Fine needle aspiration biopsy (FNA) is frequently used to make an
initial tissue diagnosis of a head and neck cancer when a patient presents with a neck mass
(metastatic cervical lymph node) without an obvious primary mucosal/upper aerodigestive tract
site. This technique has high sensitivity and specificity and a diagnostic accuracy that ranges from
89 to 98 percent [9-11]. Nondiagnostic aspirations occur in 5 to 16 percent of cases, most
commonly in cystic neck masses, as is common in the presentation of patients with HPV associated
oropharyngeal cancers. If an initial FNA is negative from a suspicious neck node, repeat FNA may
be considered before doing an excisional biopsy. (See "Head and neck squamous cell carcinoma of
unknown primary".)

Fine needle aspiration biopsy of a suspected involved lymph node in the setting of an established
primary tumor may provide relevant information when clinical and imaging evaluation of neck
lymph nodes is equivocal and a positive or negative finding would change the clinical treatment
approach (eg, RT field or dose, or the use of concurrent chemoradiotherapy versus RT alone).
Several studies have compared ultrasound plus ultrasound-guided FNA biopsy to neck computed
tomography (CT); the procedures were comparable in terms of overall accuracy (88 and 85
percent in one series compared to 69 percent by palpation) [12,13], while others noted better
results with FNA [14,15]. In one report of 86 patients with clinically node-negative (N0) necks,
ultrasound with FNA detected malignancy in five who did not fulfill radiologic criteria for
malignancy by CT scan [16]. Conversely, several enlarged nodes on CT scan were negative by
cytology (ie, they potentially represented a false-positive finding).PET may also have a role in the
evaluation of cervical lymph nodes. (See 'PET and integrated PET/CT' below.)

Another promising strategy for increasing the accuracy of overall staging is sentinel lymph node
biopsy [17-20]. Like cutaneous melanoma, this technique utilizes preoperative
lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel lymph node
biopsy is a reliable and reproducible method for staging the clinically and radiologically N0 neck in
patients with early stage head and neck cancer. It also may have use in determining the best
treatment for contralateral N0 neck in patients with midline malignancies and node positive
ipsilateral disease. Sentinel lymph node biopsy is technically feasible, reliable (high sensitivity if the
three highest intensity nodes are sampled), oncologically safe, and associated with less morbidity
than elective neck dissection. Despite these findings, this technique is not yet widely used clinically
in the United States.

Imaging studies — Imaging studies (computed tomography [CT] magnetic resonance imaging

[MRI], PET, and integratedPET/CT) are important for assessing the degree of local infiltration,
involvement of regional lymph nodes, and presence of distant metastases or second primary
tumors.

CT scan — CT can identify tumors of the head and neck based upon either anatomic distortion or
specific tumor enhancement (image 1). In general, tumors enhance more than normal head and
neck structures except for mucosa, extraocular muscles, and blood vessels [21]. Compared with
MRI, CT provides greater spatial resolution, and can be performed with faster acquisition times,
thereby virtually eliminating motion artifact, and it is better for the evaluation of bone destruction.

Modern multidetector CT technology allows scanning to be performed with slice thickness less
than 1 mm. Slice thickness of 3 mm is generally optimal, while slice thickness greater than 5 mm
does not offer sufficient spatial resolution. Images should be reconstructed and viewed in both
soft tissue and bone windows. Dental amalgam can create severe beam hardening image artifacts
that obscure image details in the scan plane. This problem can be remedied by rescanning the
obscured area with angulated gantry.

●Primary site — For cancers of the oral cavity, contrast-enhanced CT can help determine the
extent of tumor infiltration into deep tongue musculature and whether or not the mandible is
involved. For other head and neck cancers, CT is particularly useful in upstaging cancers that have
deeper local invasion or infiltration into adjacent structures that is difficult to detect on physical
examination. CT can provide information on invasion of the preepiglottic space, laryngeal cartilage,
paraglottic space and subglottic extension, and can evaluate retropharyngeal, parapharyngeal,
upper mediastinal, and paratracheal nodes. In addition, bone and cartilage invasion, a criterion for
stage T4 disease, can be more readily detected.

Distinction of cartilage invasion from non-ossified cartilage can be a difficult task for conventional
CT. The new technology of dual energy and multispectral CT has demonstrated improved accuracy
for assessing cartilage invasion compared with conventional CT [22]. Preliminary results have
demonstrated an increase of specificity for evaluation of thyroid cartilage invasion from 70 to 96
percent, with no compromise of sensitivity (86 versus 86 percent) [22,23]. In general, the
advantage of improved tissue characterization offered by dual-energy and spectral CT may
enhance the accuracy of CT for evaluation of tumor extent and staging [24].
In one review of 81 patients with head and neck cancer, CT resulted in a change in assigned clinical
stage in 54 percent of cases [25]. This was most likely to occur with hypopharyngeal tumors and
least likely with glottic laryngeal tumors (90 and 16 percent, respectively).

●Regional nodes — Imaging by CT or MRI is complementary to the clinical examination for the
staging of the neck lymph nodes. CT evaluation of regional lymph nodes primarily relies upon size
criteria as well as the appearance of lymph nodes to differentiate involved from uninvolved lymph
nodes. The use of size criteria alone results in frequent false positive and false negative
assessment of regional nodes. CT is also highly sensitive for detection of extracapsular spread of
tumor.

Pathologic lymphadenopathy is usually defined radiologically as a node greater than 10 to 11 mm

in minimal axial diameter or one that contains central necrosis [26,27]. The choice of how a lymph
node is measured is often controversial and reflects a tradeoff between sensitivity and specificity.
In general, criteria based on measurement of minimal axial diameter are considered the most
accurate and effective [28,29], and probably most reproducible [30]. Other features that suggest
pathological lymph nodes include rounded shape, loss of normal fatty hilum, and increased or
heterogeneous contrast enhancement. In one study, data from 47 consecutive patients with head
and neck cancer (total of 53 neck dissections) were combined with findings from a 15-year
MEDLINE review of the English-language literature to compare physical examination with CT scan
[31]. CT was superior to physical examination in terms of sensitivity (83 versus 74 percent),
specificity (83 versus 81 percent), accuracy (83 versus 77 percent), and detection of pathologic
cervical adenopathy (91 versus 75 percent).

Although CT is superior to physical examination, the use of size criteria and the presence of central
necrosis are limitations that prevent detection of borderline-sized nodes, nonnecrotic nodes, or
extracapsular spread confined within the radiologically-defined margin of nodes. These cannot be
differentiated by CT from reactive or normal nodes [26]. This is an important issue since
microscopic or occult nodal adenopathy is not unusual in head and neck cancer.

In one series of 957 lymph nodes from patients with head and neck cancer, 102 (11 percent)
harbored malignant cells [32]. The following findings were noted in terms of nodes that would not
be called malignant by CT:

•Sixty-seven percent of tumor-containing nodes were 10 mm or smaller.

•Twenty percent of malignant nodes had extracapsular spread; almost one-third of these nodes
were 10 mm or smaller and some were less than 5 mm.

•Central necrosis was found primarily in nodes larger than 20 mm, suggesting that it is a late event
in metastatic adenopathy.

•Extracapsular spread of nodal metastasis is an important prognostic factor that should be

assessed on imaging. Imaging findings that suggest extracapsular spread of nodal metastasis
include irregular border of the lymph node, infiltration of adjacent fat planes, and loss of cleavage
plane with adjacent anatomical structures.
Magnetic resonance imaging — MRI provides superior soft tissue definition compared with CT [33]
and can often provide information that is complementary to CT. For example, MRI can provide
more accurate definition of tumors of the tongue and is more sensitive for superficial tumors. MRI
is also better than CT for discriminating tumor from mucus and in detecting bone marrow invasion
[34]. For this reason, MRI can be useful for evaluation of cartilage invasion, particularly for non-
ossified cartilage that can pose difficulty for CT. On the other hand, CT scanning is better than MRI
for detection of bone cortex invasion since MRI shows no bony detail. The availability of dual
energy and multispectral CT, however, may decrease the advantage of MRI in cartilage evaluation
[22,23], although a direct comparison between MRI and dual energy CT has not been reported.

MRI is superior to CT for evaluation of perineural spread, skull base invasion, and intracranial
extension of head and neck cancer. MRI may also provide additional benefits compared with CT in
the evaluation of the base of tongue and parotid glands.

Most important imaging sequences for head and neck imaging include non-contrast enhanced T1-
weighted images, contrast-enhanced T1-weighted images with fat suppression, and T2-weighted
images with fat suppression. Images in axial and coronal plane are the most useful. For general
purpose, slice thickness should be no more than 5 mm. Some applications, such as evaluation of
skull base and perineural spread, may require thinner slice thickness, typically around 3 mm.

In most studies, CT scanning outperforms MRI for the detection of pathologic nodal metastases.
The reported sensitivity of MRI is as low as 57 to 67 percent. However, neither test reliably detects
clinically occult regional node involvement.

PET and integrated PET/CT — With PET, injected positron-emitting radionuclides, such as fluorine-
18, are taken up by metabolically or functionally active tissues. PET images are created by
detecting these emissions by an array of detectors and then using reconstruction techniques to
create a three dimensional image. The most commonly used agent is 18F-flourodeoxyglucose
(FDG), which is taken up into cells in different concentrations depending on the relative
metabolism of different tissues. It is fairly specific for tumors because metabolic rates are very
high in many tumors.

Imaging of the primary tumor site and regional lymph nodes with PET is limited by its poor spatial
resolution, which can make it difficult to localize the anatomic location of the FDG uptake. These
issues can be at least partially addressed with integrated PET-CT imaging, in which PET and CT are
performed sequentially during a single visit on a hybrid PET-CT scanner. The images are then
coregistered using fusion software, enabling the physiologic data obtained on PET to be localized
according to the anatomic CT images.

Historically, CT images obtained from integrated PET-CT scanners had lower spatial resolution
compared with dedicated CT scanners. This problem is now being overcome by new generation of
PET-CT scanners that offer volumetric CT capability

PET appears to be at least as sensitive and specific as CT and MRI in detecting primary head and
neck tumors [35-38]   More importantly, PET is superior to both CT and MRI for detecting regional
nodal metastases, as well as distant metastases and second primary tumors [39-41].
Despite these data, the value of PET is uncertain for patients with a clinically negative (N0) neck, a
reflection of its limitations in detecting occult nodal metastases less than 5 mm. The sensitivity of
PET is lower in this setting (25 to 51 percent in four separate studies [42-45]), although at least one
series reports better results [46]. Some of this disparity may be due to the detail with which
resected lymph nodes are examined pathologically [47].

When used for the initial staging of head and neck cancer, integrated PET-CT imaging appears
superior to CT, MRI, or PET alone:

●In one series of 30 patients with newly diagnosed head and neck cancer, PET-CT (98 percent) was
better than CT (70 percent) and MR alone (80 percent) in identifying primary tumor invasion of
specific anatomical structures. Findings on PET-CT imaging altered management in 7 of 30 patients
(23 percent) [15]. Similar findings have been reported by others [48,49].

●The superiority of PET-CT in evaluating the cervical nodes was shown in a series in which
integrated PET-CT was compared to CT alone in 63 patients with newly diagnosed head and neck
cancer [50]. While CT alone identified 14 of 17 diseased heminecks (82 percent sensitivity) and 9 of
9 negative heminecks (specificity 100 percent), PET-CT detected metastatic disease in all 17
diseased heminecks and in 26 of 27 nodal zones that were histologically positive at the time of
dissection.

●In a second report of 68 patients (52 with a squamous cell cancer of the head or neck, 8 with a
squamous cell cancer of unknown origin, and 8 with recurrent or metastatic thyroid cancer), six
proven malignancies were missed by PET, but only one was missed with PET-CT [51]. Of the 157
foci with abnormal FDG uptake, the fraction of equivocal lesions decreased by 53 percent with the
integration of PET and CT (from 39 of 155 with PET to 18 of 157). Findings on PET-CT changed the
treatment plan in 12 patients (18 percent).

●In a retrospective report of 123 patients with previously untreated head and neck cancer who
underwent pretreatmentPET/CT, the scan was true positive in 103 (83 percent), while 15 (12.2
percent) had a false-positive study at the primary or elsewhere [52]. Synchronous lesions were
found in 10 patients (8.3 percent) and distant metastases in 19 (15.4 percent). Of the 40
heminecks that underwent dissection, PET was positive in 19 of the 22 involved sides (sensitivity
86 percent) and it was negative in 16 of 17 uninvolved sides (specificity 96 percent). Overall,
management was altered in 38 patients (31 percent) as a result of the PET scan. The originally
planned surgery was canceled (19 patients, 15 percent) because of metastatic disease or finding a
primary tumor residing outside of the head and neck region.

●False negatives of PET may be seen in lymph nodes less than 5 mm, necrotic or cystic lymph
nodes, and tumors of low metabolic activity.

Taken together, these data indicate that PET/CT is accurate for detecting occult cervical nodal
metastases, although it does not have the sensitivity to replace neck dissection. Its main utility is in
finding occult distant metastases, unknown primary lesions, and synchronous second primary
tumors, as well as altering radiation fields and doses for patients who are not undergoing neck
dissection. (See 'Evaluation for distant metastases' below.)
Evaluation for distant metastases — A component of the initial staging evaluation for patients with
new or recurrent head and neck cancer is the search for distant metastases. The reported
incidence is between 2 and 26 percent and varies based on locoregional control, nodal
involvement (number and presence of extracapsular extension), primary site (particularly
hypopharynx), histologic grade, and T stage [53-56].

Distant metastases at initial diagnosis are usually asymptomatic; the most common sites are the
lungs followed by the liver and bone. Screening tests such as chest x-ray, serum alkaline
phosphatase, and liver function tests are insensitive to the presence of distant metastases [57-59].

Until recently, CT scan was the most sensitive method to screen for distant metastases in patients
with head and neck cancer, identifying malignant findings in between 4 and 19 percent of newly
diagnosed cases [59-65]. Although chest CT detects distant metastases more frequently than chest
x-ray, it fails to detect the 2 to 5 percent of patients who will have distant metastases outside the
chest [60,66,67].

PET and integrated PET/CT have greatly replaced other tests for detection of distant metastases
and synchronous second primary tumors [48,66-71]. However, false-positive findings are common,
underscoring the need to undertake histologic confirmation of any sites of abnormal
uptake. PET/CT is sensitive and superior for evaluation of deep lesions, while panendoscopy is
highly accurate for evaluation of smaller or more superficial second primary mucosal
lesions.PET/CT and direct mucosal inspection therefore play important complimentary roles in the
work-up of head and neck cancers. (See 'PET and integrated PET/CT' above.)

These issues can be illustrated by a series of 349 patients with head and neck tumors who
underwent preoperativehead/neck CT or MRI and whole body PET-CT [69]. Further diagnostic
imaging was guided by the results of the PET-CT scan. Overall there were 14 second primary
tumors (4 percent) and 26 patients with distant metastases (7.4 percent) detected during staging
or within 15 months of surgery. PET-CT correctly identified all but one (a patient with CT-
demonstrable metastases in the lungs and gluteus muscle). However, there were 23 false-positive
PET-CT results. Overall, the sensitivity, specificity, positive predictive value and negative predictive
value were 98, 93, 63, and 99.7 percent, respectively.

Incidence of second and multiple primaries — At-risk patients (ie, those with strong tobacco and
alcohol use or family history) are prone to develop second primary cancers of the upper
aerodigestive tract. Such tumors may be present at presentation or develop subsequently. (See
"Second primary malignancies in patients with head and neck cancers".)

Future molecular staging methods — Analyzing differences in gene expression patterns across

individual patients with a certain type of cancer may reveal molecular differences that permit
refinements in their classification, prognostication, and treatment selection. At least some data
suggests that primary head and neck cancers may carry specific molecular changes that are
capable of predicting the presence of (or potential for) cervical nodal metastases [72,73].
However, these approaches remain investigational. (See "Overview of gene expression profiling,
proteomics, and microRNA profiling in clinical oncology".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The
Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable with
some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a variety
of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient information: Mouth sores (The Basics)" and "Patient information:
Tongue cancer (The Basics)" and "Patient information: Laryngeal cancer (The Basics)" and "Patient
information: Throat cancer (The Basics)")

SUMMARY

●Head and neck cancer encompasses a variety of cancers, mostly squamous cell carcinomas,
which can arise in the oral cavity, pharynx, larynx, or salivary glands. The initial symptoms and
subsequent staging depend upon the site of the primary tumor.

•(See 'Clinical presentation' above and 'TNM staging system' above.)

•See individual tumor sites for more detailed discussions of different primary sites.

●Proper staging of the primary tumor, regional lymph nodes, and exclusion of distant metastases
is required for developing an optimal treatment plan. The initial assessment of the primary tumor
includes a combination of inspection, palpation, indirect mirror examination, and direct
endoscopy. An examination under anesthesia should generally be performed to define the extent
of the tumor and to take biopsies for a tissue diagnosis. (See 'Initial evaluation' above.)

●Imaging studies (computed tomography [CT] magnetic resonance imaging [MRI], positron
emission tomography [PET], and integrated PET/CT) are important to assess the degree of local
infiltration, involvement of regional lymph nodes, and presence of distant metastases or second
primary tumors. The evaluation of the regional lymph nodes has improved significantly with the
development of improved imaging modalities such as integrated PET/CT, but these approaches
still can miss more limited degrees of tumor involvement.

All patients should have a staging CT scan or MRI of the head and neck (although CT scan of the
brain is not needed). The role of a routine PET scan in staging of all patients is less clear but should
be considered in patients at high risk for metastatic disease or with equivocal findings on CT or
MRI scan, or those at increased risk of second malignancy (especially those with a smoking history)
who are not having an operative panendoscopy (laryngoscopy, esophagoscopy, bronchoscopy).
Panendoscopy may not be needed if PET scan is performed, particularly when the PET scan is
negative [8,74]. (See 'Imaging studies' above.)

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