• Anteriorly the posterior choanae.
• Posteriorly the clivus and the first 2 cervical vertebrae.
• Superiorly the floor of the sphenoid.
• Inferiorly the level of the free border of the soft palate.
• Divided into 3 subsites:
1. The posterosuperior wall
2. The lateral walls
3. The posterosuperior surface of the soft palate.
• The torus tubarius is the opening of the eustachian
tube into the lateral nasopharyngeal wall.
• The fossa of Rosenmüller is the groove or recess
posterior to the torus at the junction between the
lateral and posterior walls (Nasopharyngeal carcinoma
(NPC) most commonly occurs in this location).
• The nasopharynx is an anatomically difficult area to
expose surgically. This area is in close proximity to
several foramina and associated vital neurovascular
structures. These include the foramen ovale, the
foramen spinosum, the foramen lacerum, the carotid
canal, and the jugular foramen.
• Ho originally described the supraclavicular
fossa as a triangular region defined by 3
1. the sternal end of the clavicle
2. the lateral end of the clavicle
3. the point where the neck meets the shoulder.
• This area is clinically significant in that any
nodal involvement within this triangle is, by
definition, an N3 lesion and, therefore, stage
• Neck mass (most common initial symptom, 70%).
• Serous otitis media from eustachian tube obstruction (second most
common presentation, 50%).
• Nasal obstruction.
• Cranial nerve palsies (abducent nerve most common cranial nerve
palsy) Villaret's syndrome
• Recurrent epistaxis.
• Trismus, headache.
• Regional distribution (Southern China,
Northern Africa, Southeast Asia, Alaska,
• Epstein-Barr Virus (EBV) Viral Capsule Antigen (VCA):
late antigen, most specific immunological finding in nasopharyngeal cancer
• Genetic predisposition (genotypes HLA-A2 and
• Nitosamines (smoked meat and salted fish).
Staging (based on the AJCC Staging)
• T1: primary tumor confined to nasopharynx
• T2: primary tumor extension into nasal fossa or
oropharynx (without parapharyngeal extension [T2a],
with parapharyngeal extension [T2b])
• T3: invasion of bony structures or paranasal sinuses
• T4: invasion into intracranium, cranial nerves,
infratemporal fossa, hypopharynx, or orbit
World Health Organization (WHO) Classification
• WHO Type I: Keratinizing Squamous Cell Carcinoma,
squamous differentiation, not associated with EBV, worse
prognosis, less sensitive to radiation.
• WHO II: Nonkeratinizing Squamous Cell Carcinoma, does
not demonstrate definite squamous differentiation,
associated with EBV, better prognosis, sensitive to radiation
• WHO III: Undifferentiated (includes lymphoepitheliomas,
anaplastic, and clear cell variants): indistinct cell margins,
may have lymphocytic stroma (lymphoepitheliomas),
associated with EBV, better prognosis, sensitive to radiation
Diagnosis is made by biopsy of the nasopharyngeal mass. Workup includes the
• Careful visual examination (by fiberoptic endoscopic examination or examination
under anesthesia [EUA]).
• Documentation of the size and location of the tumor and neck nodes.
• Evaluation of cranial nerve function including neuro-ophthalmological evaluation
and audiological evaluation.
• Computed tomographic (CT) scan or positron emission tomography (PET)-CT scan.
• Magnetic resonance imaging (MRI) to evaluate skull base invasion.
• Chemistry panel.
• Epstein-Barr virus titers.
• Stage I Nasopharyngeal Cancer:
High-dose radiation therapy to the primary tumor
site and prophylactic radiation therapy to the nodal
• Stage II Nasopharyngeal Cancer:
1. Chemoradiation therapy followed by adjuvant
2. High-dose radiation therapy to the primary
tumor site and prophylactic radiation therapy to
the nodal drainage.
• Stage III & IV Nasopharyngeal Cancer:
1. Combined chemoradiation therapy
2. Combined chemoradiation therapy followed
by adjuvant chemotherapy.
3. Altered fractionation radiation therapy.
4. Neck dissection may be indicated for
persistent or recurrent nodes if the primary
tumor site is controlled.
prognostic factors adversely influencing outcome of treatment include
• Large tumor size.
• A higher tumor (T) stage.
• The presence of involved neck nodes.
• World Health Organization (WHO) grade I.
• Long interval between biopsy and initiation of radiation therapy.
• Diminished immune function at diagnosis.
• Incomplete excision of involved neck nodes.
• Pregnancy during treatment.
• Locoregional relapse.
• High-titer antibodies to virus capsid antigen and early antigen,
especially of high IgA class that persist after therapy.
• The junction of the soft palate and hard palate
• The circumvallate papillae of the tongue
• The hyoid bone inferiorly.
• The subsites of the oropharynx:
the soft palate, base of tongue, tonsillar fossa
and pillars, and a portion of the posterior
• Squamous cell carcinoma being by far the
most common histologic type.
• The most important causative factors are
prolonged tobacco and alcohol exposure.
Potential fascial spaces
• The retropharyngeal space
• the parapharyngeal space
When invasion does occur, tumors may spread
into these potential spaces.
• Older than 45 years of age
• Throat discomfort.
• Trismus, dysphagia, and dysarthria may develop with
• Bleeding, aspiration, airway obstruction, and weight
• Neck mass (45% to 78% of patients with oropharyngeal
primaries may present with cervical adenopathy at the
time of diagnosis)
Base of tongue
• Sore throat is the most common presenting symptom.
• Difficult to visualize, and submucosal lesions are
• Digital palpation of the tongue base in patients with
persistent sore throat is thus critical in making a proper
• Presents at an advanced stage with high rates of
cervical and distant metastasis.
• The overall survival rate as low as 20%.
• More aggressive SCC than oral tongue (high
• Cervical lymph node metastasis is high.
• Almost 20% present with bilateral cervical
metastases secondary to the rich lymphatic
system of the base of tongue.
• Levels II, III, and IV are mostly involved
• 15% of cancers of the soft palate are found during
routine physical examination.
• The most common chief complaint is odynophagia.
• Visible and symptomatic earlier than other cancers of
• Cervical lymph node metastases ranges from 2% to
45%. Bilateral in 5% to 15% of patients
• Primary lymphatic drainage to level II
• The most common sites of carcinoma of the oropharynx,
contributing 75% to 80% of all oropharyngeal cancers.
• Odynophagia or dysphagia (60-80%).
• Cervical adenopathy (15-30%).
• Otalgia or bleeding.
• Posterior and deep extension may involve the pterygoid
musculature causing significant pain and trismus
• Often presents with involvement of the anterior
• Spread anteriorly or medially to involve the
retromolar trigone, buccal, and tongue base
• The lingual nerve, inferior alveolar nerve,
glossopharyngeal nerve, and mandible may
become involved just deep to the anterior
• Cervical metastasis (66% - 76%) regions II, III, and
Posterior and lateral oropharyngeal walls
• Frequently presents at an advanced stage.
• 78% of these cancers presented at a size greater than 5 cm.
• Extend either superiorly to the nasopharynx or inferiorly to
• Dysphagia (66%) and odynophagia (62%)
• Weight loss, neck pain, and hoarseness.
• Initial presentation of a neck mass was reported in 20% of
Evaluation and staging
• Size and mobility of the lesion.
• Trismus or decreased mobility of the tongue is
a sign of invasion of the pterygomaxillary
space or deep tongue muscles.
• Cranial nerves V, VII, XI, X, and XII
• The number and size of lymph nodes.
• MRI is useful for evaluating soft tissue
involvement, particularly of the tongue base
and the parapharyngeal space.
• CT is useful in evaluating invasion of bone of
the skull base or mandible.
• EUA staging and tissue Bx.
Staging (American Joint Committee on Cancer staging
for oropharyngeal carcinoma)
• TX Primary tumor cannot be assessed
• T0 No evidence of primary tumor
• Tis Carcinoma in situ
• T1 Tumor =2cm in greatest dimension
• T2 Tumor >2cm but not more than 4cm in greatest dimension
• T3 Tumor >4cm in greatest dimension or extension to lingual
surface of the epiglottis
• T4a Moderately advanced, local disease.Tumor invades the larynx,
deep/extrinsic muscle of the tongue, medial pterygoid, hard palate,
• T4b Very advanced, local disease.Tumor invades lateral pterygoid
muscle, pterygoid plates, lateral nasopharynx, or skull base or
encases the carotid artery
• An argument can be made against primary
surgical therapy for oropharyngeal cancers.
• Even early-stage carcinomas are at risk for
regional lymph node metastases.
• Traditional neck dissections often fail to address
retropharyngeal and parapharyngeal lymphatics.
• High risk of bilateral neck disease
• Because of these issues and the morbidity of surgical
resection of the oropharynx, there has been an overall
trend toward primary therapy with radiation or
chemoradiation therapy, especially for advanced
• Single-modality therapy with radiation or surgery can
achieve similar locoregional control for early and
intermediate cancers, with radiotherapy generally
yielding better functional outcomes.
• Many institutions therefore recommend radiation
therapy for early-stage disease and chemoradiation
therapy for intermediate- and advanced-stage disease.
• Reserved for patients who have failed primary
radiation or chemoradiation or not candidates
for such therapy.
• The key factor in any approach is adequate
• Generally, all approaches are accompanied by
a neck dissection and a tracheostomy.
• The simplest, NO scars but poor exposure.
• Success depends on the size and location of the tumor.
• Preferred method for excising smaller lesions of the
soft palate, posterior pharyngeal wall, tonsil and
anterior pillar, and uvula.
• Recently, transoral laser approaches have been
described for treatment of small lesions of the base of
• May be considered for large tumors of the
base of tongue or tonsil
• Access oropharynx from a transoral incision of
the floor of the mouth
• Preserves mandibular integrity
• Poor exposure, chin numbness
Mandibular swing approach
• Wide exposure of the entire oropharynx.
• Mandible should not be involved.
• Mandibular osteotomies are performed anterior to the
mental foramen, preserving the sensory innervation of
the lip and chin.
• The floor of mouth is released along with the
lateralized mandibular segment, while preserving the
lingual nerve in its course if uninvolved.
• For oropharyngeal cancers that involve the mandible,
composite resection of the mandible and oropharynx may
• This resection is achieved with by lip-splitting or a visor flap
• Approached laterally or medially with a lip-splitting incision
• Provides excellent exposure, easier soft tissue closure.
• Risk of malocclusion and plate extrusion.
• Most appropriate for small neoplasms of the
midline base of tongue.
• Entering the pharynx above the hyoid bone
into the vallecula.
• The tumor is excised inferiorly to superiorly.
The lateral pharyngotomy approach
• The pharynx is entered between the hypoglossal
and superior laryngeal nerves.
• A rather limited view of the tongue base can be
improved by extending into a suprahyoid
approach, thus giving an excellent view of the
base of tongue and pharyngeal walls.
• Inadequate for lesions extending superiorly to the
tonsillar fossa or retromolar trigone region.
• The transcervical transpharyngeal approaches
have the advantage of minimally disrupting
existing functional anatomy while providing
adequate exposure for selected posterior
• They may be combined, if necessary, for
exposure but require some experience to be
Reconstruction of the oropharynx
• Objective of reconstruction is to restore functional
speech and swallowing while providing an adequate
• Primary closure, is reserved for small defects where
minimal tethering will be created, such as early lesions
of the base of tongue where transpharyngeal
approaches have been employed.
• Skin grafting is usually limited to lesions along the
posterior and lateral pharyngeal wall where a bolster
can be placed.
• The pectoralis major myocutaneous flap is
extremely reliable and provides sufficient bulk
to fill major defects of the oropharynx.
• Other pedicled flaps described for
reconstruction of the oropharynx include the
latissimus dorsi flap and the trapezius
• Pedicled flaps work best where mobility and
sensation are less critical, such as in the tonsil
and lateral pharyngeal regions.
• Microvascular free tissue transfer including The radial
forearm flap, based on the radial artery, provides a
thin, pliable, and possibly sensate reconstructive
option; and The lateral arm flap, based on the
posterior radial collateral artery, is another option for
reconstruction of the oropharynx.
• These flaps are most effectively used in tongue base
and palatal defects where mobility is essential to
• Bony microvascular free tissue may be used such as the
fibular or scapular osteofasciocutaneous free flap if
mandibulectomy is needed.
• Several prospective, randomized studies provide
strong data demonstrating a statistically
significant improvement in locoregional control
and a strong trend for improved overall survival
with concomitant chemoradiation therapy over
radiation therapy alone for patients with
advanced oropharyngeal carcinoma.
• Better regional and distant tumor control.
• Extends from the level of the hyoid bone to the esophageal
• It is intimately associated with the larynx, surrounding its
posterior and lateral borders.
• The subsites of the hypopharynx include the pyriform sinus,
the posterior pharyngeal wall, and the postcricoid region.
• The superior aspect of the pyriform sinus is surrounded by
the thyrohyoid membrane through which the internal
branch of the superior laryngeal nerve passes.
• Sensory portions of this nerve synapse along with
sensory nerves of the external auditory canal
(Arnold’s nerve) leading to symptoms of referred
• The postcricoid region lies posterior to the
arytenoid cartilages and cricoid ring, terminating
at the junction between the pharynx and
• The posterior pharyngeal wall of the
hypopharynx begins at the level of the hyoid
bone continuing also to the pharyngoesophageal
• Has a muscular wall consisting of the middle and
inferior constrictor muscles.
• The retropharyngeal space posterior to the
hypopharynx, which contains lymphatics and
loose areolar tissue, separates the visceral
compartment of the neck from the prevertebral
muscles with their overlying prevertebral fascia.
• The hypopharynx has a rich lymphatic supply
with its major lymphatic drainage pattern to the
jugular chain and retropharyngeal lymph nodes
and the node of Rouviere.
• Cancers of the hypopharynx are uncommon,
representing only about 0.5% of all malignancies.
• Most cancers of the hypopharynx are squamous
cell carcinoma in histology.
• Have a strong association with alcohol and
tobacco abuse and, more recently, with chronic
• Sore throat
• Neck mass (25%)
• 70% of patients will have palpable adenopathy on initial
Evaluation and staging
• Indirect pharyngolaryngoscopy (Tumors of the
posterior wall or upper pyriform sinus).
• Flexible fiberoptic examination
• Edema, erythema, pooling of secretions, and loss of
laryngeal crepitus are important signs of
• Vocal cord invasion with limited mobility is a sign of
• Palpation of the neck is necessary for evaluation
• Direct laryngoscopy, esophagoscopy, and biopsy
under general anesthesia to facilitate accurate
evaluation and staging as well as allowing
identification of possible synchronous tumors.
• CT and MRI scans are important for further
evaluation of the primary site (eg, for laryngeal
cartilage erosion) as well as evaluation for the
presence of cervical lymphadenopathy.
American Joint Committee on Cancer staging for
• T1 Tumor limited to one subsite of hypopharynx and 2 cm or less in
• T2 Tumor invades more than one subsite of hypopharynx or an adjacent
site, or measures more than 2 cm but not more than 4 cm in greatest
diameter without fixation of hemilarynx
• T3 Tumor more than 4 cm in greatest dimension or with fixation of
• T4a Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland,
esophagus, or central compartment soft tissue
• T4b Tumor invades prevertebral fascia, encases carotid artery, or involves
The mainstay of treatment in advanced cancer of the
hypopharynx remains surgery followed by radiation
• Patient’s performance status.
• Extent of disease.
• Laryngeal involvement.
• Presence of lymph node metastasis.
Only very select patients with tumors of the hypopharynx
are amenable to conservation laryngeal surgery.
Contraindications to conservation laryngeal
• Thyroid cartilage invasion.
• Involvement of the apex of the pyriform sinus.
• Involvement of the postcricoid region.
• Impairment of vocal cord motion.
Lesions of the postcricoid region, laryngectomy
is almost always required.
• Total laryngectomy with partial or total pharyngectomy
followed by postoperative radiation therapy are the
most common surgical procedures performed for
advanced squamous cell carcinoma of the hypopharynx
• Preservation of the larynx has been reported to be
possible in less than 50% of Small T1 and T2 tumors
arising from the medial wall of the pyriform sinus.
• Elective neck dissection should be performed at the
time of surgery because of the high incidence of
bilateral occult cervical metastasis + Rouviere’s node
• Primary closure or skin grafting may be used for small
defects (Posterior pharyngeal wall lesions).
• The pectoralis major myocutaneous flap or radial
forearm free flap may be used for reconstruction of
subtotal hypopharyngeal defects.
• After total laryngopharyngectomy, a free jejunal flap or
a tubed radial forearm free flap provides an excellent
method of reconstruction
• In a total laryngopharyngectomy defect where
the distal esophageal stump lies inferior to the
sternal notch, gastric interposition may be
1. Major abdominal surgery.
2. Extensive mediastinal dissection.
3. Operative morbidity is nearly 50%.
4. Mortality rates have been reported to reach
Chemotherapy and radiation therapy
• Early-stage disease Radiation therapy
results comparable to conservation surgical
• Advanced disease Radiation therapy alone
was inferior to surgery combined with
postoperative radiation therapy.
• An organ-preservation protocol using
chemotherapy is another option for improving
results of therapy for advanced disease.
• Induction chemotherapy followed by
definitive radiation therapy, reserving surgery
• Tumor response to chemotherapy may need
to be taken into account before radiation
therapy is chosen instead of surgery.
• The overall prognosis for patients with
squamous cell carcinoma of the hypopharynx
is poor because most of these patients
present at an advanced stage, and many
patients succumb to distant disease. Overall,
• Patients with late-stage hypopharyngeal
carcinoma treated with curative intent have a
5-year survival of approximately 35%.