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Advanced HNSCC requires multimodal

imaging for appropriate, multidisciplinary

treatment planning and follow up.

Irena Orlov. Industrial feel 5673. Digital on canvas, 40" × 60".

Multimodal Imaging of Head and Neck Squamous Cell Carcinoma

Kenneth L. Gage, MD, PhD, Kerry Thomas, MD, Daniel Jeong, MD, Dexter G. Stallworth, MD,
and John A. Arrington, MD

Background: The role of imaging in the staging, treatment planning, and ongoing surveillance of patients
with head and neck squamous cell carcinoma (HNSCC) continues to evolve. Changes in patient demographics,
treatment paradigms, and technology present opportunities and challenges for the management of HNSCC.
Methods: The general indications and usage of standard and multimodal cross-sectional imaging in the evalu-
ation and management of HNSCC are reviewed, with an emphasis on incorporating them into treatment path-
ways. Emerging imaging technologies and methods with a potential near-term impact on HNSCC are discussed.
Results: In general, the complex, multidisciplinary approach to the treatment of advanced HNSCC requires
multimodal imaging for adequate treatment planning and follow up. Early-stage disease can often be man-
aged with clinical and endoscopic examinations and a single, cross-sectional imaging modality (eg, computed
tomography, magnetic resonance imaging).
Conclusions: Although generalized treatment pathways and guidelines do exist, the literature is rapidly
advancing and new radiotracers and evaluation methods are expected to alter both imaging and treatment
recommendations in the years to come.

Background is estimated to be greater by an order of magnitude,

In the United States, head and neck cancers are expect- with 686,000 new cases diagnosed and 375,000 related
ed to account for 3.7% (63,030 new cases) of all can- deaths.2 Head and neck cancers encompass a broad
cers diagnosed in 2017.1 In that same year, an estimated range of tumor histologies and locations. However,
13,360 Americans will die as a result of tumors involv- more than 90% of head and neck cancers are squa-
ing the oral cavity, pharynx, and larynx.1 The world- mous cell carcinomas, arising from the upper aerodi-
wide incidence of new cases of head and neck cancers gestive tract and frequently involving the oral cavity,
oropharynx, hypopharynx, and larynx.2 Although the
From the Diagnostic Imaging and Interventional Radiology overall rate of new cases of oropharyngeal cancer in
Program (KLG, KT, DJ, DGS, JAA), H. Lee Moffitt Cancer Center the United States has been stable or decreasing, cases
& Research Institute, and the Departments of Oncologic Sciences linked to human papillomavirus (HPV) continue to
(JAA) and Radiology (JAA), University of South Florida College of
Medicine, Tampa, Florida. rise, altering the demographics and presentation of
Address correspondence to John A. Arrington, MD, Moffitt new cases of head and neck squamous cell carcinoma
Cancer Center, 12902 Magnolia Drive, WCB-RAD MD/OPI, (HNSCC).3
Tampa, FL 33612. E-mail:
Because of its low contribution to the overall can-
Submitted November 10, 2016; accepted March 28, 2017.
cer incidence in the United States, the true impact of
No significant relationships exist between the authors and the
companies/organizations whose products or services may be HNSCC on public health may be under-represented.1
referenced in this article. No widely accepted screening test exists for HNSCC,

172 Cancer Control April 2017, Vol. 24, No. 2

and many patients present with advanced-stage dis- Primary Site
ease, requiring disfiguring surgery, chemoradiothera- The extent of mucosal involvement by the primary tu-
py, or both. Both timely diagnosis and accurate staging mor is best documented through clinical and endoscop-
of HNSCC are critical to avoid under- or overtreatment ic examinations, whereas imaging is obtained to evalu-
and to minimize mortality and morbidity. Thus, the ob- ate submucosal and deep, soft-tissue extension as well
jective of this review is to summarize the role of imag- as osseous, cartilaginous, or skull-base involvement.
ing in the management of HNSCC throughout the con- The location of the primary site of disease can in-
tinuum of care while also providing clinical examples fluence the selection of modalities for initial imaging
highlighting the strengths and weaknesses of each assessment. For example, MRI is often the preferred
imaging modality (magnetic resonance imaging [MRI], imaging modality for evaluating the oral cavity, es-
contrast-enhanced computed tomography [CT], and pecially the anterior tongue, retromolar trigone, and
positron emission tomography [PET]/CT). the floor of the mouth, in which dental hardware and
beam-hardening artifact can limit the usefulness of
Role of Imaging CT (Fig 1).6,7 MRI provides superior soft-tissue contrast
Since the introduction of CT and MRI, the role of imag- and allows the detection of suspicious changes in bone
ing in HNSCC has grown. The widespread application marrow, aiding in the evaluation of the adjacent man-
of fludeoxyglucose F 18 (18F-FDG) positron emission dible and other osseous structures when tumor inva-
tomography (PET) in the late 1990s added a functional sion is suspected. MRI is considered the best imaging
metabolic component to imaging, with the subsequent modality for assessing perineural tumor spread, intra-
fusion of functional (PET) and anatomical (CT) imag- cranial and orbital extension (Fig 2), nasopharyngeal
ing in the combined modality of PET/CT resulting in carcinoma, and marrow involvement.
further improvements in disease management.4 Con- However, the superior, soft-tissue contrast provided
tinued technological progress and the broadening by MRI of the head and neck is not without its own limi-
applications further increase the role of diagnostic tations. The intense inflammatory response surround-
imaging in the evaluation and management of HN- ing some lesions highlighted with contrast-enhanced
SCC. PET/CT, contrast-enhanced CT, and MRI have MRI can lead to difficulties in determining the true ex-
well-defined strengths and weaknesses and, therefore, tent of disease, thus complicating treatment approaches
play complementary roles in the evaluation and treat- and radiation fields (Fig 3). In some cases, the true lesion
ment planning of HNSCC. However, no single imaging burden is better delineated with functional techniques
modality can accurately diagnose, stage, and provide such as PET/CT. In addition, the relative scarcity of ex-
long-term surveillance of HNSCC. citable protons in the osseous matrix results in minimal
signal from cortical bone, which may limit the detection
Initial Staging
Accurate initial staging is critical to the establishment
of prognosis, treatment selection, and the manage-
ment of HNSCC. Guidelines issued by the American
Joint Commission on Cancer represent the standard
for HNSCC staging and require detection and precise
delineation of the patient’s primary tumor (T), cer-
vical nodal involvement (N), and distant metastases
(M) for classifying patients, a process known as TNM
staging.5 These guidelines provide separate staging C D
criteria based on the mucosal site of origin, separat-
ing patients into those with cancers of the lip and oral
cavity, pharynx, and larynx.5 The resulting prognostic
stage groupings range from stages I to IV and also in-
clude substages.5
In general, diagnostic imaging complements the
clinical evaluation of the primary tumor and regional
cervical lymph nodes and can be used to detect me- Fig 1A–D. — A man aged 63 years with an infiltrating, destructive mass
involving the right mandible from right retromolar trigone squamous
tastases and second primary tumors in patients with cell carcinoma. (A) Axial, contrast-enhanced CT reveals the limited le-
HNSCC. Following an initial clinical examination and sion visibility from beam-hardening artifact on CT, even from primarily
endoscopy of the upper aerodigestive tract with biop- left-sided dental hardware. (C) Coronal imaging allow improved visu-
alization of the mandibular destruction; however, contrast-enhanced,
sy, staging is refined with diagnostic imaging and final- T1-weighted, fat-suppressed imaging (B and D) provides better repre-
ized with the pathological evaluation of cervical lymph sentation of the true extent of soft-tissue involvement in this case.
nodes from nodal dissection, if performed. CT = computed tomography.

April 2017, Vol. 24, No. 2 Cancer Control 173

and accurate characterization of osseous destruction on with cervical nodal metastasis, distant metastasis, or
MRI (Fig 4). In these cases, diagnostic CT is often con- both types of metastases have worse prognoses and
sidered the best imaging modality for lesion assessment. decreased 5-year survival rates when compared with
those without metastatic disease.1 The importance of
Locoregional and Nodal Disease nodal status for overall prognosis and management
The most important factor that affects prognosis is cer- is such that debate remains as to when elective neck
vical nodal status, and an accurate assessment is criti- dissections or irradiation should be performed, with
cal to the treatment plan and choice of therapy. Patients a 20% or greater risk of occult, microscopic nodal dis-
ease often used as a threshold for prophylactic treat-
ment.8 Imaging detection (or exclusion) of clinically oc-
cult nodal metastasis, distant metastasis, or both types
of metastases may alter the treatment plan, thus reduc-
ing rates of unnecessary surgery and therapy as well as
associated morbidity and cost.
Diagnostic imaging adds to the clinical evaluation
of cervical nodal involvement by detecting clinically oc-
cult nodal metastases and identifying morphological
features of clinical importance (Fig 5), such as the pres-
ence of extracapsular nodal extension, vascular encase-

Fig 2A–B. — A man aged 63 years with aggressive squamous cell carci-
noma involving the skull base. (A) Sagittal, contrast-enhanced computed A B
tomography reveals a destructive, centrally hypoenhancing mass at the
skull base with unclear involvement of the intracranial structures. (B) Con-
trast-enhanced, T1-weighted, fat-suppressed imaging obtained at a similar
orientation demonstrates dural enhancement, increasing clinical suspicion
for intracranial tumor growth. The carotid artery was also circumferentially
involved and narrowed (not shown), which is a poor prognostic sign.


Fig 4A–B. — A man aged 63 years with aggressive squamous cell carcinoma
involving the skull base (same patient as Fig 2). (A) Sagittal, contrast-enhanced
CT imaging reconstructed with a bone algorithm reveals sclerosis of the skull
base (red arrow) and cortical destruction in the more posterior temporal bone
(red arrowheads). (B) Contrast-enhanced, T1-weighted, fat-suppressed MRI
obtained in a similar plane also demonstrates significant marrow enhance-
ment along the area of sclerosis seen on CT; however, the osseous destruction
is not well appreciated on MRI when compared with CT (red arrow).
CT = computed tomography, MRI = magnetic resonance imaging.


Fig 3A–D. — (A) Contrast-enhanced, T1-weighted, fat-suppressed and

(B) T2-weighted, fat-suppressed axial imaging of a woman aged 55 years
with aggressive squamous cell carcinoma involving the right pterygoids
and their osseous structures. (A) T1-weighted imaging reveals the pres-
ence of a hypoenhancing, possibly necrotic component (red arrow), but Fig 5A–B. — (A) Axial, contrast-enhanced CT and (B) fludeoxyglucose F 18
the overall degree of enhancement obscures the exact extent of dis- PET/CT demonstrating an ill-defined mass (red arrows) obliterating the fat
ease. (B) T2-weighted, fat-suppressed imaging delineates the lesion mar- planes deep into the right sternocleidomastoid muscle in a man aged 52 years
gins (red arrowheads), closely correlating with the findings on (C) fludeox- with human papillomavirus-positive squamous cell carcinoma. PET/CT imag-
yglucose F 18 PET/CT. (D) Magnetic resonance imaging poorly demarcates ing suggests low-level, possibly nonspecific activity; however, the absence
the extent of bone destruction (yellow arrow), which is best illustrated on of clear fat planes and the infiltrative appearance of the lesion on contrast-
the CT component of PET/CT imaging (C and D). enhanced CT suggest extracapsular nodal disease, a poor prognostic factor.
CT = computed tomography, PET = positron emission tomography. CT = computed tomography, PET = positron emission tomography.

174 Cancer Control April 2017, Vol. 24, No. 2

ment, and “matted” lymphadenopathy (loss of the fat the detection of nodal metastases, the absolute physi-
plane between ≥ 3 adjacent lymph nodes with extracap- cal limitations of the imaging technology can result in
sular tissue).9,10 In general, contrast-enhanced CT and false-negative results for nodes measuring less than
MRI are superior for detecting nodal anatomic features 1 cm.13 In addition, the nonspecific nature of hyper-
and provide an excellent anatomical road map for sur- metabolic activity can confound PET/CT interpreta-
gical planning; PET/CT demonstrates excellent overall tion. Elevated concentrations of 18F-FDG can occur in
sensitivity for the presence of nodal metastatic disease. post-treatment infection and localized inflamma-
The detection of small, nonclustering nodal metas- tion but are also observed during the initial staging
tases can be challenging when using anatomical imag- process. Oftentimes, PET/CT does not adequately de-
ing approaches such as CT or MRI. Criteria have been lineate deep soft-tissue extension or osseous involve-
established for the assessment of cervical lymph nodes ment, and therefore may not provide an adequate ana-
using both modalities; these criteria attempt to balance tomical road map for surgical and treatment planning.
the sensitivity and specificity of various nodal features, High-resolution, cross-sectional imaging with contrast-
with size being the dominant component.11 Of course, enhanced CT or MRI provides the anatomical details
size is not the single imaging feature of interest, and the and soft-tissue contrast necessary for therapy.
high spatial resolution and standard use of contrast for
both CT and MRI provide improved anatomical defini- Distant Metastatic Disease
tion, which readily reveals suspicious morphological Distant metastases are estimated to be extant in 10% to
features such as those previously described. The rising 15% of patients at the time of HNSCC presentation and
prevalence of HPV-positive status in patients with HN- can profoundly alter treatment.14 In such cases, local-
SCC has led to an increase in patients presenting with ized surgery and radiotherapy with curative intent are
cystic lymph-node metastases, which can be difficult to abandoned and management directed toward a pallia-
appreciate on PET/CT due to the minimal metabolic ac- tive, systemic approach.
tivity in the cystic component but are easily visualized Screening for metastatic disease at the time of
on contrast-enhanced CT and MRI (Fig 6).12 the initial diagnosis is a generally well accepted use
Although PET/CT has superior overall accuracy for of PET/CT for the initial evaluation of advanced head
and neck cancers, with PET/CT demonstrating superi-
or sensitivity for the detection of distant metastases as
well as second primary cancers.15 In patients for whom
PET/CT is unavailable or not clearly indicated, those
with HNSCC and higher-stage lesions will still often re-
ceive imaging beyond the anatomical limitations of the
head and neck. In general, head and neck cancers tend
to have distant metastases to the lungs, with nasopha-
ryngeal carcinoma proving to be the exception with
osseous metastases.16 In these instances, patients will
often undergo dedicated, contrast-enhanced CT of the
C D chest due to the increased risk of metastatic disease.14

Despite the approaches for initial TNM staging, several
questions remain as to the most appropriate approach
for evaluating patients with less-common clinical pre-
sentations such as occult primary lesions and those
presenting without palpable cervical adenopathy.
Cancer of Unknown Primary: Patients with
HNSCC can present with cervical adenopathy from an
Fig 6A–D. — (A) Axial and (C) coronal, contrast-enhanced CT imaging of
the skull base and neck reveal faintly enhancing, primary oropharyngeal occult primary lesion despite thorough clinical or en-
squamous cell carcinoma (HPV/p16 positive) at the right tongue base doscopic evaluation, a situation termed carcinoma of
(arrowhead) with a cystic, right, level 2A metastatic lymph node (red unknown primary (CUP).17 Historically, CUP was a rare
arrow) in a man aged 59 years. (B, D) Fludeoxyglucose F 18 PET/CT imag-
ing shows intense uptake in the primary lesion, but significantly less presentation of patients with HNSCC, especially as the
uptake in the cystic node when compared with an adjacent subcentime- use of multimodal imaging became widespread.18 How-
ter, tumor-containing level 2 node (yellow arrow). HPV-positive nodes ever, the increasing prevalence of HPV-positive disease
may become cystic and have low-level, nonspecific metabolic activity
on PET/CT. has led to an increase in CUP, possibly due to the ten-
CT = computed tomography, HPV = human papillomavirus, PET = positron dency of these tumors to have increased nodal disease
emission tomography. burden with small or occult primary lesions.12,19

April 2017, Vol. 24, No. 2 Cancer Control 175

PET/CT has been shown to have superior sensi- contrast-enhanced CT and MRI.25-28 One meta-anal-
tivity compared with contrast-enhanced CT and com- ysis found similar diagnostic accuracy rates between
bined CT/MRI for the detection of occult primary le- MRI, CT, PET, and ultrasonography for the detection
sions, with the added advantage of its ability to detect of occult disease in the setting of a clinically negative
distant metastatic disease and synchronous second neck.29 However, data from Roh et al,30 who conducted
malignancies (Fig 7).20 In addition, PET/CT can locate a prospective clinical trial, found PET/CT to have supe-
infraclavicular sites of primary disease when primary rior sensitivity for the detection of clinically occult, cer-
head and neck cancer is not the source of adenopathy, vical metastatic disease compared with CT/MRI (71%
and it has been recommended for the workup of pa- vs 50%), a finding that highlights the importance of
tients when standard clinical and imaging approaches the improved anatomical localization seen in the com-
are unable to identify a primary site of disease.21,22 bined PET/CT approach.4,31 Although it is an active area
Management of “true” CUP remains challenging, of research, PET/CT may be reaching the point where
with panendoscopy, tonsillectomy, and “blind” biopsies certain neck dissections may be avoided or — at the
of lymphoid tissue advocated as possible approaches to very least — minimized, thus resulting in decreased as-
identify occult primary lesions when diagnostic imag- sociated costs and morbidity.30
ing is unable to provide a potential target.23,24 Second Primary Malignancies: Patients with
Clinically Negative Neck: Patients can present HNSCC are at significant risk of second (synchronous)
with symptomatic primary lesions without palpable or metachronous primary malignancies, which can
nodal metastatic disease, a situation termed clinically present at the initial diagnosis, during treatment, and
negative neck (staged cN0 in the TNM staging system). at follow-up visits; these malignancies are estimated
These cases are diagnostically challenging because the to occur in approximately 12% of cases.32 Presumably,
nodal status of the patient is of primary importance for these tumors are multifactorial in origin, with environ-
disease prognosis and management. mental factors (eg, use of tobacco, alcohol), infectious
Use of PET/CT for the evaluation of the clinically agents (eg, Epstein–Barr virus, HPV), and location of
negative neck is controversial, especially for early- the primary lesion potentially playing a role in deter-
stage disease: Historical studies have been unable to mining where and how frequently these lesion occur.32
discern a significant advantage of PET or PET/CT over The impact of second primary malignancies on
more traditional, cross-sectional imaging such as overall patient survival is significant.32 Approximate-
ly 75% of patients with HNSCC and second prima-
ry cancers will have those second primary cancers
outside of the head and neck region, primarily in-
volving the lungs.32 Therefore, it is imperative that
infraclavicular imaging (contrast-enhanced CT of the
chest, whole-body PET/CT, or whole-body MRI) be
pursued for select patients.
Whole-body imaging is the standard approach
for PET/CT in patients with HNSCC, unlike the lim-
ited field of view used for MRI and CT imaging. The
extended anatomical field of PET/CT provides an
C D advantage for detecting both distant metastatic dis-
ease and second primary malignancies outside of the
head and neck, with pooled sensitivity and specificity
rates estimated to be 88.8% and 95.1%, respectively.16
Whole-body MRI offers the potential to detect metastat-
ic disease and second primary malignancies without
the need for ionizing radiation; however, comparative
studies in the pretreatment setting found no statistical
difference between PET/CT and whole-body MRI.33
Fig 7A–D. — (A) Axial and (B) sagittal fludeoxyglucose F 18 PET/CT and
(C) axial and (D) sagittal, contrast-enhanced, magnetic resonance im- Residual or Recurrent Disease
aging of a man aged 51 years with human papillomavirus/p16-positive
primary squamous cell carcinoma at the right base of the tongue. PET/CT Patients with HNSCC who receive treatment may be
detected a small lesion (red arrows) that was otherwise poorly seen. cured of disease, harbor residual neoplasms at treat-
PET/CT can be useful in situations such as this where the primary malig- ment sites, experience locally recurrent disease, or de-
nancy cannot be found. (A) Low-level activity in the left jugulodigastric
chain was also seen (yellow arrow), highlighting the nonspecific activity velop distant metastatic disease or new second prima-
that can also complicate evaluation in cases of head and neck cancers. ry malignancies (local or distant). Evaluation of these
CT = computed tomography, PET = positron emission tomography. patients requires an approach that accounts for the sta-

176 Cancer Control April 2017, Vol. 24, No. 2

tistical likelihood of local and distant disease and ap- mean glycolytic volume, and many others.39
propriately leverages imaging. Despite the search to associate individual quanti-
Detection of malignant disease (residual, recur- tative, continuous variables with clinically significant
rent, or second primary malignancies) in the treat- prognostic outcomes, studies have indicated that there
ed head and neck can be challenging. Soft-tissue is value in more qualitative assessments such as the
changes and anatomical disfigurement seen after visual pattern of metabolic activity.38,40,41 For example,
surgery, chemotherapy, radiotherapy, or all 3 cours- qualitative metrics by Koyasu et al38 characterized le-
es of management can distort the intricate anatomy sions as having ring-shaped (ie, central decreased ac-
of the head and neck, thereby limiting sensitivity for tivity) vs sphere-shaped distributions of 18F-FDG and
detecting residual or recurrent disease. PET/CT has demonstrated a robust prediction of outcomes in their
been suggested as the best modality for assessment of the cohort. Mathematically characterizing these qualitative
post-treatment or altered neck, although appropriate tim- measures is the focus of the field of radiomics, an area
ing of follow-up PET/CT imaging (generally 12 weeks of study that has had some success in head and neck
after treatment) is required to mini-
mize false-positive findings from A B C
residual, treatment-related hyper-
metabolic activity (Fig 8).34 PET/
CT with iodinated intravenous
contrast has several diagnostic
advantages but is not routinely
used at most institutions.35
In addition to the challenge
of detecting locoregional fail-
ure on follow-up examination,
patients with HNSCC may be at
significant risk for distant meta-
static disease and remote primary
cancers, especially patients with Fig 8A–C. — Imaging in a man aged 52 years with head and neck squamous cell carcinoma negative
for human papillomavirus. (A) Beam-hardening effect from dental hardware limits evaluation of the
higher-stage malignancies.14 oropharynx and adjacent structures on contrast-enhanced CT. (B) Combined PET/CT is less affected
PET/CT was found to have high by beam hardening and reveals nonspecific, diffuse activity post partial glossectomy. (C) Repeat
sensitivity and specificity rates imaging several months later reveals more focal, intense, radiotracer accumulation in the posterior
and anterior tongue and floor of the mouth, subsequently determined to be recurrent disease.
(92% and 95%, respectively) for
CT = computed tomography, PET = positron emission tomography.
detecting distant metastatic dis-
ease in patients suspected of hav-
ing recurrent HNSCC (Fig 9).36 A B
Protocols for whole-body MRI
have also been used and com-
pared with PET/CT for the evalu-
ation of HNSCC in the post-treat-
ment setting; however, superiority
was not demonstrated of either C
modality, although a trend was
observed toward greater diagnos-
tic accuracy with PET/CT.37

Emerging Applications
Prognostic Evaluation With D
Functional Imaging
Several efforts have been pub-
lished regarding the use of quanti-
tative 18F-FDG PET/CT measures
as prognostic factors for head and
neck cancers.38 These quantitative Fig 9A–D. — A woman aged 55 years with recurrent squamous cell carcinoma of the right maxillary
sinus, negative for human papillomavirus and Epstein–Barr virus (same patient seen in Fig 3), now
measures include the mean, max, involving the pterygoids and mandible. (A) Maximum intensity projection, (B) CT, (C) 18F-FDG PET,
and peak of the standardized up- and (D) 18F-FDG PET/CT imaging reveal evidence of numerous, distant pulmonary metastases.
take value, total glycolytic volume, 18F-FDG = fludeoxyglucose F 18, CT = computed tomography, PET = positron emission tomography.

April 2017, Vol. 24, No. 2 Cancer Control 177

cancers and can potentially offer a more generalizable, evaluation provided by magnetic resonance imaging
systematic approach.40,41 (MRI) or contrast-enhanced CT result in the most com-
prehensive imaging evaluation of head and neck squa-
New Radiotracers mous cell carcinoma (HNSCC). The complete evalua-
Use of PET/CT has traditionally focused on 18F-FDG, tion provided by combined modalities (PET/CT with or
a positron-emitting radiotracer that follows the ini- without contrast-enhanced CT or MRI) is often needed
tial steps of glucose metabolism and takes advantage for the management of advanced (stage III/IV) HN-
of the propensity of malignant cells to preferentially SCC, which generally requires multidisciplinary treat-
utilize aerobic glycolysis as an energy source, the ment encompassing surgery, radiotherapy, and che-
so-called Warburg effect.42 There is an increasing as- motherapy. Fludeoxyglucose F 18 PET/CT has become
sortment of radiotracers targeting alternate pathways the imaging cornerstone for evaluating these patients,
(fluorothymidine F 18, cellular proliferation), receptor with the decision being whether to utilize contrast-en-
targets, and tumor environmental conditions (fluo- hanced CT or MRI for anatomical details. Early-stage
romisonidazole F 18, tumor hypoxia) that may prove cancers, on the other hand, are often adequately im-
useful for further characterizing HNSCC in patients.43-45 aged and staged with a single modality, usually con-
trast-enhanced CT. Established imaging guidelines are
Discussion in constant flux as new imaging paradigms, radiotrac-
The medical literature outlines well-defined roles for ers, and therapies are introduced and evaluated, and it
the various imaging modalities for the evaluation, is expected that quantitative imaging approaches will
management, and surveillance of HNSCC. Although begin to play a more important role in the manage-
these roles are generally accepted by multidisciplinary ment of HNSCC.
clinical services, variability exists between institutions
regarding which imaging modality or modalities are References
useful for specific clinical situations. Surgeon and ra- 1. American Cancer Society. Cancer Facts & Figures 2017. Atlanta:
American Cancer Society; 2017.
diologist preference, availability, cost, health insurance /cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and
coverage, and the patient’s clinical condition will im- -figures/2017/cancer-facts-and-figures-2017.pdf. Accessed March 29, 2017.
2. Stewart BW, Wild C, eds. World Cancer Report. Lyon, France: Inter-
pact imaging choices and utilization. national Agency for Research on Cancer; World Health Organization; 2014.
Treatment pathways developed at Moffitt Cancer 3. Deschler DG, Richmon JD, Khariwala SS, et al. The “new” head
and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive:
Center and elsewhere provide guidance regarding the evaluation. Otolaryngol Head Neck Surg. 2014;151(3):375-380.
timing, frequency, and recommended protocols for 4. Beyer T, Townsend DW, Brun T, et al. A combined PET/CT scanner
for clinical oncology. J Nucl Med. 2000;41(8):1369-1379.
the various imaging modalities used for the manage- 5. Edge S, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual.
ment of HNSCC.46 At Moffitt Cancer Center, we utilize 7th ed. New York: Springer; 2010.
6. Rumboldt Z, Gordon L, Bonsall R, et al. Imaging in head and neck
contrast-enhanced CT as the mainstay of our cross- cancer. Curr Treat Options Oncol. 2006;7(1):23-34.
sectional imaging in patients with HNSCC and utilize 7. Escott EJ. Role of positron emission tomography/computed tomography
(PET/CT) in head and neck cancer. Radiol Clin North Am. 2013;51(5):881-893.
MRI as a “problem solver” or in specific clinical situa- 8. Corry J, Rischin D, Hicks RJ, et al. The role of PET-CT in the man-
tions such as perineural tumor spread or intracranial agement of patients with advanced cancer of the head and neck. Curr Oncol
Rep. 2008;10(2):149-155.
or orbital extension, as well as for the evaluation of 9. Spector ME, Gallagher KK, Light E, et al. Matted nodes: poor prog-
postoperative patients with abnormal findings on PET/ nostic marker in oropharyngeal squamous cell carcinoma independent of
HPV and EGFR status. Head Neck. 2012;34(12):1727-1733.
CT and a normal clinical examination. The utilization 10. Spector ME, Chinn SB, Bellile E, et al. Matted nodes as a predictor
of MRI and contrast-enhanced CT is determined by pa- of distant metastasis in advanced-stage III/IV oropharyngeal squamous
cell carcinoma. Head Neck. 2016;38(2):184-190.
tient-specific clinical concerns and questions that need 11. Som PM. Detection of metastasis in cervical lymph nodes:
to be answered by imaging. PET/CT is initially used in CT and MR criteria and differential diagnosis. AJR Am J Roentgenol.
patients with higher T-staged disease at Moffitt Cancer 12. Subramaniam RM, Alluri KC, Tahari AK, et al. PET/CT imaging and
Center to identify second primary malignancies and human papilloma virus-positive oropharyngeal squamous cell cancer:
evolving clinical imaging paradigm. J Nucl Med. 2014;55(3):431-438.
distant metastases, as well as in the post-treatment and 13. Yamazaki Y, Saitoh M, Notani K, et al. Assessment of cervical
surveillance settings to detect treatment failure and lymph node metastases using FDG-PET in patients with head and neck
cancer. Ann Nucl Med. 2008;22(3):177-184.
recurrence. Patient and disease-specific factors often 14. Ferlito A, Shaha AR, Silver CE, et al. Incidence and sites of distant
lead to the adjustment of pathway recommendations, metastases from head and neck cancer. ORL J Otorhinolaryngol Relat
Spec. 2001;63(4):202-207.
which are usually addressed on a case-by-case basis 15. Ng SH, Chan SC, Liao CT, et al. Distant metastases and synchro-
during multidisciplinary tumor boards. nous second primary tumors in patients with newly diagnosed oropharyn-
geal and hypopharyngeal carcinomas: evaluation of (18)F-FDG PET and
extended-field multi-detector row CT. Neuroradiology. 2008;50(11):969-979.
Conclusions 16. Xu GZ, Guan DJ, He ZY. (18)FDG-PET/CT for detecting distant
metastases and second primary cancers in patients with head and neck
The functional and physiological advantages of posi- cancer. A meta-analysis. Oral Oncol. 2011;47(7):560-565.
tron emission tomography (PET)/computed tomogra- 17. Issing WJ, Taleban B, Tauber S. Diagnosis and management of
carcinoma of unknown primary in the head and neck. Eur Arch Otorhino-
phy (CT) combined with the cross-sectional anatomi- laryngol. 2003;260(8):436-443.
cal details, superior soft-tissue contrast, and osseous 18. Strojan P, Ferlito A, Medina JE, et al. Contemporary management

178 Cancer Control April 2017, Vol. 24, No. 2

of lymph node metastases from an unknown primary to the neck: I. A review 2014;28(10):1020-1026.
of diagnostic approaches. Head Neck. 2013;35(1):123-132. 44. van Dijk LK, Boerman OC, Kaanders JH, et al. PET imaging in head
19. Motz K, Qualliotine JR, Rettig E, et al. Changes in unknown primary and neck cancer patients to monitor treatment response: a future role for
squamous cell carcinoma of the head and neck at initial presentation in EGFR-targeted imaging. Clin Cancer Res. 2015;21(16):3602-3609.
the era of human papillomavirus. JAMA Otolaryngol Head Neck Surg. 45. Zschaeck S, Haase R, Abolmaali N, et al. Spatial distribution of FMISO
2016;142(3):223-238. in head and neck squamous cell carcinomas during radio-chemotherapy
20. Lee JR, Kim JS, Roh JL, et al. Detection of occult primary tumors and its correlation to pattern of failure. Acta Oncol. 2015;54(9):1355-1363.
in patients with cervical metastases of unknown primary tumors: comparison 46. National Comprehensive Cancer Network. NCCN Clinical Practice
of (18)F FDG PET/CT with contrast-enhanced CT or CT/MR imaging- Guidelines in Oncology: Head and Neck Cancers. V1.2017. Published
prospective study. Radiology. 2015;274(3):764-771. February 6, 2017.
21. Hermans R. Imaging in cervical nodal metastases of unknown primary. /head-and-neck.pdf. Accessed April 13, 2017.
Cancer Imaging. 2011;11(A):S9-S14.
22. Fletcher JW, Djulbegovic B, Soares HP, et al. Recommendations on
the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49(3):480-508.
23. Koch WM, Bhatti N, Williams MF, et al. Oncologic rationale for bilat-
eral tonsillectomy in head and neck squamous cell carcinoma of unknown
primary source. Otolaryngol Head Neck Surg. 2001;124(3):331-333.
24. Kothari P, Randhawa PS, Farrell R. Role of tonsillectomy in the
search for a squamous cell carcinoma from an unknown primary in the
head and neck. Br J Oral Maxillofac Surg. 2008;46(4):283-237.
25. Nahmias C, Carlson ER, Duncan LD, et al. Positron emission
tomography/computerized tomography (PET/CT) scanning for preoper-
ative staging of patients with oral/head and neck cancer. J Oral Maxillofac
Surg. 2007;65(12):2524-2535.
26. Ng SH, Yen TC, Chang JT, et al. Prospective study of [18F]fluorode-
oxyglucose positron emission tomography and computed tomography and
magnetic resonance imaging in oral cavity squamous cell carcinoma with
palpably negative neck. J Clin Oncol. 2006;24(27):4371-4376.
27. Schöder H, Carlson DL, Kraus DH, et al. 18F-FDG PET/CT for
detecting nodal metastases in patients with oral cancer staged N0 by
clinical examination and CT/MRI. J Nucl Med. 2006;47(5):755-762.
28. Schroeder U, Dietlein M, Wittekindt C, et al. Is there a need for posi-
tron emission tomography imaging to stage the N0 neck in T1-T2 squamous
cell carcinoma of the oral cavity or oropharynx? Ann Otol Rhinol Laryngol.
29. Liao LJ, Lo WC, Hsu WL, et al. Detection of cervical lymph node
metastasis in head and neck cancer patients with clinically N0 neck-a meta-
analysis comparing different imaging modalities. BMC Cancer. 2012;12:236.
30. Roh JL, Park JP, Kim JS, et al. 18F fluorodeoxyglucose PET/CT
in head and neck squamous cell carcinoma with negative neck palpation
findings: a prospective study. Radiology. 2014;271(1):153-161.
31. Branstetter BF, Blodgett TM, Zimmer LA, et al. Head and neck
malignancy: is PET/CT more accurate than PET or CT alone? Radiology.
32. Birkeland AC, Rosko AJ, Chinn SB, et al. Prevalence and outcomes
of head and neck versus non-head and neck second primary malignancies
in head and neck squamous cell carcinoma: an analysis of the Surveillance,
Epidemiology, and End Results database. ORL J Otorhinolaryngol Relat
Spec. 2016;78(2):61-69.
33. Chan SC, Wang HM, Yen TC, et al. 18F-FDG PET/CT and 3.0-T
whole-body MRI for the detection of distant metastases and second primary
tumours in patients with untreated oropharyngeal/hypopharyngeal carcinoma:
a comparative study. Eur J Nucl Med Mol Imaging. 2011;38(9):1607-1619.
34. Fukui MB, Blodgett TM, Snyderman CH, et al. Combined PET-CT in
the head and neck: part 2. Diagnostic uses and pitfalls of oncologic imaging.
Radiographics. 2005;25(4):913-930.
35. King KG, Kositwattanarerk A, Genden E, et al. Cancers of the oral
cavity and oropharynx: FDG PET with contrast-enhanced CT in the post-
treatment setting. Radiographics. 2011;31(2):355-373.
36. Gao S, Li S, Yang X, Tang Q. 18FDG PET-CT for distant metastases
in patients with recurrent head and neck cancer after definitive treatment.
A meta-analysis. Oral Oncol. 2014;50(3):163-167.
37. Ng SH, Chan SC, Yen TC, et al. PET/CT and 3-T whole-body MRI in
the detection of malignancy in treated oropharyngeal and hypopharyngeal
carcinoma. Eur J Nucl Med Mol Imaging. 2011;38(6):996-1008.
38. Koyasu S, Nakamoto Y, Kikuchi M, et al. Prognostic value of pre-
treatment 18F-FDG PET/CT parameters including visual evaluation in
patients with head and neck squamous cell carcinoma. AJR Am J Roentgenol.
39. Chung MK, Jeong HS, Son YI, et al. Metabolic tumor volumes
by [18F]-fluorodeoxyglucose PET/CT correlate with occult metastasis in
oral squamous cell carcinoma of the tongue. Ann Surg Oncol. 2009;16(11):
40. Aerts HJ, Velazquez ER, Leijenaar RT, et al. Decoding tumour
phenotype by noninvasive imaging using a quantitative radiomics approach.
Nat Commun. 2014;5:4006.
41. Leijenaar RT, Carvalho S, Hoebers FJ, et al. External validation of
a prognostic CT-based radiomic signature in oropharyngeal squamous cell
carcinoma. Acta Oncol. 2015;54(9):1423-1429.
42. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis?
Nat Rev Cancer. 2004;4(11):891-899.
43. Hoshikawa H, Yamamoto Y, Mori T, et al. Predictive value of
SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT
for short-term outcome with head and neck cancers. Ann Nucl Med.

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