Overview of treatment for head and neck cancer

Authors
Bruce E Brockstein, MD
Kerstin M Stenson, MD, FACS
Shiyu Song, MD, PhD
Section Editors
Marshall R Posner, MD
Marvin P Fried, MD, FACS
David M Brizel, MD
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: Jan 14, 2015.

INTRODUCTION — Most head and neck cancers begin in the mucosal surfaces of the upper
aerodigestive tract and these are predominantly squamous cell carcinomas.

An overview of treatment for head and neck squamous cell carcinomas will be presented here. An
overview of the diagnostic approach and staging of head and neck cancers is presented separately.
(See "Overview of the diagnosis and staging of head and neck cancer".)

Malignancies arising in other organs within the head and neck regions are discussed in the
relevant site-specific topics.

INTEGRATED APPROACH TO MANAGEMENT — A multidisciplinary approach is required before

therapeutic intervention for planning treatment and managing these patients. This should include
surgeons, medical oncologists, and radiation oncologists, as well as
dentists, speech/swallowing pathologists, dieticians, and rehabilitation therapists.

Furthermore, treatment of complex cases of head and neck cancer should be treated at high-
volume centers whenever possible, where expertise in each of these disciplines may be better [ 1].
An analysis of outcomes from a large randomized trial (RTOG 0129) found that patients treated at
centers with historically high accrual to head and neck clinical trials had a significantly better five-
year overall survival rate compared with those treated at centers with historically low accrual (69
versus 51 percent) [2]. These differences could not be explained based upon differences in the
prognostic factors of enrolled patients.

ANATOMIC SUBSITES — Head and neck cancers arise from a variety of sites within the head and
neck region, which is divided into five basic areas (figure 1). These are discussed in detail
separately. (See "Overview of the diagnosis and staging of head and neck cancer", section on
'Anatomic subsites'.)

In brief:

●The oral cavity includes the lips, buccal mucosa, anterior tongue, floor of the mouth, hard palate,
upper gingiva, lower gingiva, and retromolar trigone (figure 2).
●The pharynx is divided into the oropharynx, the nasopharynx, and the hypopharynx.

•The nasopharynx, the narrow tubular passage behind the nasal cavity, is the upper part of the
pharynx.

•The oropharynx, the middle part of the pharynx, includes the tonsillar area, the tongue base, the
soft palate, and the posterior pharyngeal wall.

•The hypopharynx, which is the lower part of the pharynx, includes the pyriform sinuses, the
posterior surface of the larynx (postcricoid area) and the inferoposterior, and inferolateral
pharyngeal walls.

●The larynx contains the vocal cords and epiglottis. It is divided into three anatomic regions: the
supraglottic larynx, the glottic larynx (true vocal cords and the anterior and posterior
commissures), and the subglottic larynx (figure 3 and figure 4).

●The nasal cavity and the paranasal sinuses, which include the maxillary, ethmoid, sphenoid, and
frontal sinuses (figure 5).

●The major salivary glands (parotid, submandibular, and sublingual (figure 6)) and the minor
salivary glands, which are located throughout the submucosa of the mouth and upper
aerodigestive tract, including the oral cavity (especially the palate), paranasal sinuses, larynx, and
pharynx.

TNM STAGING SYSTEM — The tumor node metastases (TNM) system of the American Joint
Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC) is used to stage
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 "Tumors of the nasal cavity" and "Cancer of the
nasal vestibule", section on 'Staging' and "Paranasal sinus cancer", section on 'Diagnosis and
staging')

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

The approach to the diagnosis and staging of head and neck cancer is discussed separately. (See
"Overview of the diagnosis and staging of head and neck cancer", section on 'Diagnosis and staging
evaluation'.)

MANAGEMENT OF SQUAMOUS CELL CARCINOMAS

Localized (early stage) disease — Approximately 30 to 40 percent of patients with head and neck
squamous cell carcinomas present with stage I or II (early stage) disease. In general, these patients
are treated with either primary surgery or definitive radiation therapy (RT). Patients with
carcinoma in situ usually are managed surgically in the same way as those with T1 disease.

Five-year overall survival in patients with stage I or stage II disease is typically from 70 to 90
percent. Careful observation and follow-up after initial treatment are required both to detect a
potentially curable recurrence and to identify and treat second primary tumors. Particularly in
patients with tobacco and alcohol-related head and neck cancers, there is a substantial increase in
the risk of a second head and neck cancer as well as of a second primary arising in the lung.
Smoking cessation should be pursued in smokers. (See "Second primary malignancies in patients
with head and neck cancers" and "Overview of smoking cessation management in adults".)

RT and surgery result in similar rates of local control and survival for many sites; the choice of
therapy is typically based upon the specific site and its requirements, surgical accessibility of the
tumor, and the functional outcomes and morbidity associated with each modality. Oral cavity
cancers are a notable exception and are usually best treated with surgery based upon generally
better cure rates and toxicity profile compared with radiation based therapy. External beam RT or
brachytherapy may be options, especially if surgical expertise is not available.

Traditional surgical approaches through skin incisions to gain access to the mucosal primary (ie,
wide local excision) are usually used for oral cavity, salivary, and thyroid cancers, which are easily
accessible. At other sites, minimally invasive techniques, such as transoral laser microsurgery
(TOLM) for larynx and hypopharynx cancers and transoral robotic surgery (TORS) for oropharynx
cancers, have improved transoral access. These approaches can improve functional outcomes and
decrease morbidity, compared with standard surgical approaches.

Definitive RT approaches include external beam RT and brachytherapy. Curative RT treatment

requires three-dimensional conformal technique at a minimum. Highly conformal radiation
techniques, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have
demonstrated reduced morbidity and represent current best practice where available. (See
"General principles of radiation therapy for head and neck cancer", section on 'Three-dimensional
conformal RT'.)
For patients initially treated with surgery, postoperative RT with or without concurrent
chemotherapy is indicated for advanced stage cancers, close or positive margins, and other factors
that increase the risk of local recurrence, including perineural invasion and lymphovascular
invasion. The finding of multiple lymph nodes on elective lymph node dissection in the clinically N0
patient is likewise an indication for radiation. (See "Postoperative radiation therapy in the
management of head and neck cancer".)

Specific recommendations for pretreatment evaluation and treatment are described according to
the head and neck squamous cell carcinoma site.

●(See "Treatment of early (stage I and II) head and neck cancer: The oral cavity".)

●(See "Treatment of early (stage I and II) head and neck cancer: The oropharynx", section on
'General principles'.)

●(See "Treatment of early (stage I and II) head and neck cancer: The hypopharynx".)

●(See "Treatment of early (stage I and II) head and neck cancer: The larynx".)

Locoregionally advanced disease — Locoregionally advanced (stage III/IV) squamous cell

carcinoma of the head and neck is associated with a high risk of both local recurrence and distant
metastases. Combined modality approaches (surgery, radiation therapy, and/or chemotherapy)
are generally required to optimize the chances for long-term disease control [4,5].These combined
modality approaches include primary surgery followed by either postoperative RT or concurrent
chemoradiotherapy, induction chemotherapy (the addition of chemotherapy prior to
surgery and/or RT), concurrent chemoradiotherapy without surgery, and sequential therapy
(induction chemotherapy followed by concurrent chemoradiotherapy) without surgery.

Decisions about the optimal sequencing and selection of surgery, RT, and/or chemotherapy

require multidisciplinary input. Key factors to consider include the primary tumor site and disease
extent, individual patient factors (age, comorbidity, preferences regarding treatment type), and
the likely functional consequences and morbidity of each treatment approach. The choice of
therapy should also take into account the experience and technology available at the patient’s
medical institution.

●Oral cavity – Surgery is generally preferred for locoregionally advanced oral cavity squamous cell
carcinomas since most cases are easily accessible, and simultaneous resection and reconstruction
can be accomplished with acceptable functional outcomes. However, oral cavity tumors are
aggressive cancers with high rates of locoregional recurrence; thus, postoperative RT with or
without chemotherapy should be strongly considered.

Definitive RT, concurrent chemoradiotherapy, and sequential therapy are typically reserved for
patients who are medically inoperable, who have unresectable disease, or who have resectable
disease where surgical resection cannot be accomplished with acceptable long-term functional
consequences (eg, total glossectomy that may require TL to prevent aspiration).
●Oropharynx, hypopharynx, and larynx – Organ-function-sparing approaches (TORS, TOLM,
chemoradiotherapy) rather than large ablative primary surgery affecting function are preferred for
most patients with cancers of the oropharynx, hypopharynx, and larynx, even if the cancer is
potentially resectable. Concurrent chemoradiotherapy is a standard option for functional organ
preservation.

●Definitive RT alone, often using an altered fractionation schedule, remains a treatment option for
elderly patients and those with a poor performance status, as the meta-analysis showed a lack of
benefit for concurrent chemotherapy in those in their 70’s and a potential detriment for those in
their 80’s.

The efficacy, indications, and application of organ-sparing approaches are discussed separately, as
is definitive RT and postoperative RT:

●(See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining
chemotherapy and radiation therapy".)

●(See "Definitive radiation therapy alone for advanced (stage III and IV) head and neck cancer:
Dose and fractionation schedule".)

●(See "Postoperative radiation therapy in the management of head and neck cancer".)

Specific recommendations for treatment are discussed according to the primary site of disease:

●(See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The oral
cavity".)

●(See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The
oropharynx".)

●(See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx
and hypopharynx".)

Management of the neck — Head and neck squamous cell carcinomas frequently metastasize to
the cervical lymph nodes, an occurrence that has a markedly negative impact on prognosis.
Consequently, treatment of the cervical neck nodes, even if involvement is clinically occult, is often
part of the treatment strategy.

For patients with head and neck squamous cell carcinomas who have cervical lymph node
involvement at presentation and are treated with definitive RT or chemoradiotherapy,
management of residual abnormalities in the neck can be a particularly difficult issue. For patients
with complete regression as documented clinically and by structural (computed tomography [CT],
magnetic resonance imaging [MRI]) and functional (positron emission tomography [PET]) imaging,
observation is generally indicated, whereas salvage surgery is indicated in the absence of an
adequate response (algorithm 1). (See "Management of the neck following definitive radiotherapy
or without chemoradiotherapy in head and neck squamous cell carcinoma".)
The risk of developing nodal metastases varies by primary tumor site and factors such as size,
histology, tumor thickness, and perineural invasion. When the probability of occult metastases
exceeds 15 to 20 percent, the risk of neck recurrence without elective (prophylactic) treatment is
sufficiently high to outweigh the morbidity of neck dissection and/or irradiation. (See
"Management and prevention of complications during initial treatment of head and neck cancer"
and "Management of late complications of head and neck cancer and its treatment".)

Reconstruction and rehabilitation — Surgical resection of the mandible, palate, and the larynx can
lead to problems in airway management, mastication, deglutition, speech, and cosmesis. Function
is also impaired by radiation therapy and chemoradiotherapy.

●Prosthetic rehabilitation of patients with hard palate defects (the result of tumor resections
involving the maxilla) consists of placement of an obturator prosthesis, which serves to restore
orofacial functions, including deglutition, control of secretions, mastication, and phonetics, and to
aesthetically replace the missing orofacial structures. The obturator fills a defect in the palate that
causes velopharyngeal incompetency (VPI), which would otherwise allow a food bolus to go into
the sinonasal cavity, and result in a hyporesonant, non-intelligible speech quality. (See
"Management of acquired maxillary defects: Prosthetic rehabilitation after head and neck cancer
surgery".)

●Surgical reconstruction alone or combined with an obturator prosthesis can be used to remedy
palatal defects. In addition, a variety of reconstruction options, including free flaps and
autogenous (fibular) bone flaps, are available to restore mandibular defects. (See "Mandibular and
palatal reconstruction in patients with head and neck cancer".)

●Speech and swallowing rehabilitation are critical to restoring function and quality of life following
both surgery and radiation therapy. (See "Speech and swallowing rehabilitation of the patient with
head and neck cancer" and "Alaryngeal speech rehabilitation".)

Complications — Toxicity associated with treatment for head and neck cancer (whether surgery,
radiation therapy, and/or chemotherapy) is substantial and every effort should be made to
minimize side effects and treat these complications.

In addition to the acute effects associated with treatment, delayed toxicity can have an important
effect on quality of life. (See "Management and prevention of complications during initial
treatment of head and neck cancer" and "Management of late complications of head and neck
cancer and its treatment" and "Quality of life in head and neck cancer".)

Posttreatment evaluation and surveillance — Regular posttreatment follow-up is an essential part

of the care of patients after potentially curative treatment of head and neck cancer. Patients
should be educated about possible signs and symptoms of a second primary cancer and local
regional recurrence, including hoarseness, pain, dysphagia, bleeding, and enlarged lymph nodes.
(See "Posttreatment surveillance of squamous cell carcinoma of the head and neck".)

Upon completion of therapy, posttreatment imaging is important to evaluate for residual disease
and establish a baseline. Our approach is to conduct a clinical evaluation around six weeks
following RT or chemoradiotherapy and then a complete evaluation including imaging
(CT, PET/CT, or MRI) at 12 weeks to document regression of the primary tumor. Imaging should
not be performed too soon. Obtaining imaging studies, particularly PET-CT, prior to 12 weeks
following treatment can lead to an increased frequency of false positive results. CT or MRI can be
carried out at four to six weeks if needed as part of the clinical evaluation. (See "Overview of the
diagnosis and staging of head and neck cancer".)

For patients who have clinically involved cervical lymph node disease prior to RT or
chemoradiotherapy, functional imaging (PET) and structural imaging (CT/MRI) are important
components of the assessment of response to initial therapy (algorithm 1). (See 'Management of
the neck' above and "Management of the neck following definitive radiotherapy or without
chemoradiotherapy in head and neck squamous cell carcinoma".)

Following treatment, the intensity of follow-up is greatest in the first two to four years.
Approximately 80 to 90 percent of all recurrences occur within this timeframe; the risk of a second
primary malignancy is higher than recurrence risk for most patients beyond three years.

However, continued follow-up is generally suggested since the morbidity of treatment can worsen
over time and the risk of recurrence and second primary malignancy remains elevated beyond the
first five years, especially for cancers of the hypopharynx, larynx, nasopharynx, and salivary glands.
Because of the higher risk of recurrence and second primary malignancy in those who continue
tobacco use, many schedule more frequent surveillance visits for these patients and continue for
longer duration (ie, beyond five years).

Locally recurrent disease — Although most patients with recurrent disease have a poor prognosis,
those with only locoregional disease may benefit from definitive treatment.

All patients with locoregionally recurrent disease should be evaluated for distant metastases prior
to initiating retreatment. Those with a good performance status and whose disease is confined to
the head and neck may benefit from surgical salvage and/or radiation or reirradiation, although
treatment options are limited by the previous treatment received. (See "Treatment of locally
recurrent squamous cell carcinoma of the head and neck" and "Reirradiation for locally recurrent
head and neck cancer".)

Metastatic disease — Palliative chemotherapy and/or supportive care is the most appropriate

option for many patients with locally recurrent metastatic disease that is not amenable to
definitive therapy, as well as for patients who have widely disseminated disease. (See "Treatment
of metastatic and recurrent head and neck cancer".)

SPECIAL CIRCUMSTANCES — Some malignancies arising in the mucosa of the upper aerodigestive

tract have unusual histology or biology, which can have important implications for patient
management.

These are briefly discussed here, and more detailed discussions are provided in other topics, as
noted below. Non-mucosal malignancies (eg, thyroid, base of skull) are discussed in the relevant
site-specific topics.

Human papillomavirus associated oropharyngeal cancer — Human papillomavirus (HPV) infection

is a causative agent for many head and neck squamous cell carcinomas arising in the oropharynx
(tonsils and base of tongue). HPV associated cancers have increased dramatically and have
substantially altered the epidemiology of oropharyngeal squamous cell carcinoma. These tumors
define a distinct subset of patients who have frequent lymph node involvement and an improved
prognosis compared with HPV-negative, tobacco-driven oropharynx cancers. (See "Human
papillomavirus associated head and neck cancer".)

Clinical trials are underway to define the optimal treatment for these patients, with the goal of
maximizing long-term cure rates while minimizing toxicity, including treatment de-intensification.
Currently, however, the approach remains the same as for patients whose tumors are not HPV
related, and the use of HPV status in clinical decision making remains investigational.

Nasopharyngeal carcinoma — Nasopharyngeal carcinoma differs from other head and neck

cancers in its epidemiology, pathology, natural history, and treatment. (See "Epidemiology,
etiology, and diagnosis of nasopharyngeal carcinoma".)

Radiation therapy (RT) is the mainstay of treatment for locoregional nasopharyngeal cancer, but
the integration of chemotherapy has been instrumental in improving survival for most stage II, and
advanced stage disease (III and IV). Surgery is not typically used because of the deep anatomical
location of the nasopharynx and its close proximity to critical neurovascular structures and the
base of skull. (See "Treatment of early and locoregionally advanced nasopharyngeal carcinoma"
and "Treatment of recurrent and metastatic nasopharyngeal carcinoma".)

Nasal vestibule and nasal cavity cancers — Tumors of the nasal vestibule are essentially skin
cancers and are treated with surgery and/or RT, depending on size and location within the nasal
vestibule. Cancers of the nasal cavity are similar to those that occur in the paranasal sinuses, and
have a wide variety of histologies. Both early and moderately advanced tumors of the nasal cavity
are treated with surgical resection and postoperative radiation. (See "Cancer of the nasal
vestibule" and "Tumors of the nasal cavity" and "Paranasal sinus cancer".)

Paranasal sinus cancer — Paranasal sinus cancers encompass multiple histologies, with

adenocarcinoma and squamous cell carcinoma being predominant. Aggressive surgical resection
remains the mainstay of treatment, but multimodality approaches with surgery, RT, and
chemotherapy may be appropriate for certain histologies and for advanced stage cancers. (See
"Paranasal sinus cancer".)

Salivary gland cancers — Salivary gland tumors consist of a wide array of benign and malignant
histologies that occur in salivary gland tissue throughout the head and neck. Surgical resection of
the salivary gland is important both for diagnosis and treatment. Patients with benign and low-
grade tumors are typically treated with surgery alone, whereas patients with high-grade
carcinomas and other high-risk features are usually treated with surgery and postoperative RT.

●(See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)

●(See "Salivary gland tumors: Treatment of locoregional disease".)

●(See "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease".)
Squamous cell carcinoma of unknown primary — Squamous cell carcinomas of unknown primary
that involve the upper cervical lymph nodes most likely originate from a head and neck primary.
Many are squamous cell carcinomas, and are often HPV positive, suggesting an occult oropharynx
primary. Clinical, imaging, and surgical staging is required to seek a primary. Many centers are
advocating functional tongue base resection and/or tonsillectomy in order to locate the
microscopic primary site. If none is found, these are treated with curative intent using RT to the
oropharyngeal and nasopharyngeal mucosa, and the neck. In contrast, squamous cell carcinomas
involving the lower neck may represent distant metastases from a head and neck, esophagus,
lung, gastrointestinal, or genitourinary tract primary, so treatment is directed to the neck only and
individualized. Patients without other obvious sites of metastatic disease (eg, lung, liver, or bone)
should be treated with definitive therapy for locoregional disease. (See "Head and neck squamous
cell carcinoma of unknown primary".)

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 topic (see "Patient information: Throat cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Treatment for head and neck squamous cell carcinoma requires a consideration of tumor site
and stage, the functional outcomes and morbidity associated with various treatment approaches,
and patient-specific factors, such as performance status, comorbidities, and preference.

●A multidisciplinary approach, including surgeons, medical oncologists, and radiation oncologists,

as well as dentists, speech/swallowing pathologists, dieticians, and rehabilitation therapists, all
with adequate expertise, is required for planning treatment and managing these patients. (See
'Integrated approach to management' above.)

●Patients with localized (stage I and II) head and neck carcinomas are generally managed with
either surgery or radiation therapy (RT) alone. However, a combined modality may be required in
cases with high-risk features. (See 'Localized (early stage) disease' above.)

●Patients with more advanced (stage III, IVA, and IVB) disease are typically managed with a
multimodality approach, including both RT and chemotherapy; functional organ preservation
approaches are generally preferred. (See 'Locoregionally advanced disease' above and "Locally
advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy
and radiation therapy".)
●Palliative treatment and/or supportive care are appropriate for most patients with locally
recurrent and metastatic disease. However, carefully selected patients with disease confined to
the head and neck may benefit from surgical or radiation salvage and/or reirradiation. (See 'Locally
recurrent disease' above.)

●Treatment of the cervical lymph nodes, even if involvement is clinically occult, is often required.
(See 'Management of the neck' above.)

●Regular posttreatment follow-up is an essential part of the care of patients after potentially
curative treatment of head and neck cancer. (See 'Posttreatment evaluation and surveillance'
above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Benedito

Carneiro, MD, MSc, who contributed to an earlier version of this topic review.

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REFERENCES

Corry J, Peters LJ, Rischin D. Impact of center size and experience on outcomes in head and neck
1
cancer. J Clin Oncol 2015; 33:138.
Wuthrick EJ, Zhang Q, Machtay M, et al. Institutional clinical trial accrual volume and survival of
2
patients with head and neck cancer. J Clin Oncol 2015; 33:156.
American Joint Committee on Cancer Staging Manual, 7th ed, Edge SB, Byrd DR, Compton CC, et
3
al (Eds), Springer, New York 2010.
Furness S, Glenny AM, Worthington HV, et al. Interventions for the treatment of oral cavity and
4
oropharyngeal cancer: chemotherapy. Cochrane Database Syst Rev 2010; :CD006386.
Pignon JP, le Maître A, Maillard E, et al. Meta-analysis of chemotherapy in head and neck cancer
5 (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;
92:4.
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