42

NEOPLASMS OF THE
ORAL CAVITY AND
OROPHARYNX
Dennis H. Kraus, MD
John K. Joe, MD

This chapter focuses on squamous cell carcinoma, also called

epidermoid carcinoma, of the oral cavity and oropharynx.
Tumors affecting these regions have significant implications
for respiration, deglutition, and speech. The propensity for
locoregional recurrence of advanced cancers of the oral
cavity or oropharynx necessitates combined therapy, usually
surgery and adjuvant radiotherapy.

ANATOMY
The oral cavity is defined as the region from the skin–vermilion
junction of the lips to the junction of the hard and soft palate
above and to the line of the circumvallate papillae below. The
oral cavity includes the lips, buccal mucosa, upper and lower
alveolar ridges, retromolar trigone, hard palate, floor of the
mouth, and anterior two-thirds of the tongue (oral tongue).
Regional lymph node groups in the neck are grouped into
various levels for ease of description. The lateral neck is
divided into levels I through V. Metastasis to regional lymph
nodes occurs in a predictable fashion through sequential
spread. Regional lymph nodes at highest risk for metastases
from primary squamous cell carcinomas of the oral cavity
include those at levels I, II, and III, collectively known as the
supraomohyoid triangle.
496
 Neoplasms of the Oral Cavity and Oropharynx 497

The oropharynx is the midportion of the pharynx con-

necting the nasopharynx above with the hypopharynx below.
The oropharynx extends from the plane of the inferior surface
of the hard palate to the plane of the superior surface of the
hyoid bone and opens anteriorly into the oral cavity. The
oropharynx includes the base of the tongue, soft palate, ton-
sillar regions, and posterior pharyngeal wall.
The primary routes of lymphatic spread from primary
tumors of the oropharynx, hypopharynx, and larynx involve
deep jugular chain lymph nodes at levels II, III, and IV.
Midline structures such as the base of the tongue, soft palate,
and posterior pharyngeal wall commonly drain to lymphatic
channels in both sides of the neck.

EPIDEMIOLOGY AND ETIOLOGY

In the United States, the incidence of oral cavity and pha-
ryngeal cancer was estimated to number approximately
30,200 new cases in the year 2000, representing 2.5% of all
new cases of cancer.
Both tobacco and alcohol abuse independently con-
tribute to the development of cancer of the oral cavity and
oropharynx. When present together, however, the combined
effects of tobacco and alcohol abuse in the development of
oral and oropharyngeal cancer are multiplicative, rather than
simply additive.
Geographic differences in tobacco consumption may
explain the higher proportion of cancers arising from the oral
cavity and oropharynx worldwide, compared to that in the
United States. Such cultural practices include reverse smok-
ing, consumption of betel and paan, and bidi smoking.
Other risk factors implicated in carcinoma of the oral
cavity and oropharynx include viral infection with human
papillomavirus or human immunodeficiency virus (HIV), poor
socioeconomic status, neglected oral hygiene, recurrent
498 Otorhinolaryngology

trauma from ill-fitting dentures, vocal abuse, gastroesophageal

reflux, prolonged exposure to sunlight, ionizing radiation, and
dietary deficiencies of vitamin A or riboflavin.

PATHOLOGY
The risk of second primary tumors for squamous cell carci-
noma of the head and neck is approximately 4% annually, up
to 25% at 10 years.
The development of malignant tumors appears to be the
result of multiple accumulated genetic alterations. Genetic
alterations in the progression to carcinogenesis include acti-
vation of proto-oncogenes and the inactivation of tumor sup-
pressor genes. P53 is a tumor suppressor gene that plays an
important role in arresting cell growth in the presence of
genetic damage to permit deoxyribonucleic acid (DNA)
repair or lead to apoptosis. Mutations in and subsequent inac-
tivation of the P53 tumor suppressor gene may result in accu-
mulation of DNA damage and uncontrolled cellular growth.
It has been shown that the incidence of P53 mutations
increases throughout the progression from premalignant
lesions to invasive carcinomas.
Akin to the progression of genetic events leading to
phenotypic evidence of malignancy, various precancerous
lesions affect the oral cavity and oropharynx, with the poten-
tial for malignant degeneration. Leukoplakia is a clinical
descriptive term for a white patch in the oral cavity or phar-
ynx that does not rub off. The prevalence of premalignant or
malignant transformation is variable but has been estimated
at approximately 3.1%.
Erythroplasia appears as a red, slightly raised, granular
lesion in the oral cavity and oropharynx. In contrast to the
variable incidence of cancer in patients with leukoplakia, ery-
throplasia has a much higher correlation with concurrent or
subsequent malignancy.
 Neoplasms of the Oral Cavity and Oropharynx 499

Histologically, squamous cell carcinoma may be classified

into the following categories: keratinizing, nonkeratinizing,
spindle cell, adenoid squamous, and verrucous carcinoma.
Verrucous carcinoma presents as a slowly growing exo-
phytic or warty neoplasm in the oral cavity. Verrucous carci-
noma typically affects the buccal mucosa of elderly patients
with a history of tobacco exposure or poor oral hygiene. True
verrucous carcinoma does not have metastatic potential. The
recommended treatment for verrucous carcinoma is wide
surgical excision, although irradiation may be considered in
selected patients. Anaplastic transformation of verrucous
carcinoma has been reported to occur following radiation
therapy, but this theory is controversial.

MECHANISMS OF CANCER SPREAD

In general, lesions in the posterior part of the oral cavity have
a higher predilection for regional lymph node metastases than
those lesions situated more anteriorly in the oral cavity. There
is an increased risk for bilateral or contralateral metastases
from primary tumors arising from midline structures, such
as the midline lip, floor of the mouth, oral tongue, base of
the tongue, soft palate, and posterior pharyngeal wall. The
5-year survival rate of patients with cervical lymph node
metastases is approximately 50% that of patients without
regional lymph node metastases.
Extracapsular spread of carcinoma in cervical lymph nodes
portends a poor prognosis. Extracapsular extension has been
associated with increased rates of regional nodal recurrence as
well as significantly decreased survival rates. Other negative
prognostic factors with regard to regional metastases include an
increased number of involved lymph nodes, as well as spread
of tumor to lymph node levels more inferiorly in the neck.
500 Otorhinolaryngology

Distant metastases from cancers of the oral cavity and

oropharynx generally do not occur until advanced stages of
disease. Distant metastases typically involve first the lungs
or bones.

EVALUATION
The first step when evaluating a patient with cancer of the
oral cavity or oropharynx is a thorough history and compre-
hensive examination of the head and neck. The patient should
be asked about symptoms of dysphagia, odynophagia,
dysarthria, globus sensation, difficulty breathing, hemoptysis,
otalgia (possibly referred), weight loss, or other constitutional
symptoms and about consumption of tobacco and alcohol,
occupational exposures (including exposure to sunlight), and
previous radiation exposure.
There is no substitute for a systematic, comprehensive
examination of the neck, but imaging techniques such as
computed tomography (CT) or magnetic resonance imaging
(MRI) may provide valuable supplemental information
regarding the status of regional lymph nodes.
Pathologic confirmation by fine-needle aspiration biopsy
is critical for any suspicious neck mass.
Evaluation of the mandible for bony invasion by tumor
may be best accomplished by clinical examination, although
useful supplemental information may be provided by pano-
ramic films and DentaScan imaging.
Endoscopic examination of the upper aerodigestive tract
under anesthesia provides both thorough inspection of the
primary tumor and evaluation for second primary tumors,
with the ability to biopsy suspicious sites. The oropharynx,
hypopharynx, larynx, and esophagus should be examined in
a systematic fashion.
 Neoplasms of the Oral Cavity and Oropharynx 501

TREATMENT

The primary objective in treating patients with squamous

cell carcinoma of the oral cavity or oropharynx should focus
on rendering the patient free of disease. In general, early-
stage lesions may be treated by surgery or radiation with
comparable results, and more advanced cancers are best
approached with combined therapy. Further investigation
into the benefit of chemotherapy for carcinoma of the oral
cavity and oropharynx is warranted as it currently plays a
supplemental role to the established treatment modalities,
surgery and radiation.
An issue of ongoing controversy concerns the manage-
ment of the neck in patients without clinical evidence of
regional nodal metastases (the N0 neck). Elective neck dis-
section has been shown to improve locoregional control and
may therefore positively impact the quality of the patient’s
survival. In light of the morbidity associated with the radical
neck dissection, there has been a trend toward selective,
rather than comprehensive, neck dissection, based on the pre-
dictable pattern of cervical lymph node metastases. Selective
neck dissection has been demonstrated to be an oncologically
sound procedure, providing effective treatment for the N0
neck. Supraomohyoid neck dissection (SOHND), selective
lymphadenectomy clearing cervical nodal levels I, II, and III,
has been recommended for N0 patients with primary squa-
mous cell carcinomas of the oral cavity.
Based on the predictable spread of cervical nodal metas-
tases, SOHND may not be sufficient for the N0 neck with a
primary arising in the oropharynx. The risk for level IV
spread is higher from primary tumors of the oropharynx com-
pared with those arising from the oral cavity. Thus, an antero-
lateral neck dissection encompassing levels II, III, and IV of
the deep jugular chain has been advocated for N0 necks with
an oropharyngeal primary.
502 Otorhinolaryngology

For the clinically positive neck, the traditional surgical

procedure of choice has been comprehensive neck dissection
with preservation of cranial nerve XI when technically feasi-
ble. The continuing evolution of a more selective approach to
the neck, however, has included the clinically positive neck as
well. Comprehensive neck dissection, with preservation of
cranial nerve XI, the sternocleidomastoid muscle, and the
internal jugular vein, may be performed for N1, N2a, or N2b
disease when technically feasible. Supraomohyoid neck dis-
section may be acceptable for N1 disease without extracap-
sular extension arising from primaries of the oral cavity,
particularly when the involved node is at level I.

SPECIFIC SITES IN THE ORAL CAVITY

Squamous cell carcinoma of the lip by virtue of its location
tends to present at an early stage. The lower lip is affected
more commonly, presumably secondary to sunlight expo-
sure. Comparable cure rates have been reported for small
tumors using either surgery or radiation therapy, but surgi-
cal excision is the treatment of choice in most instances
owing to its lower morbidity and better cosmetic result.
Regional metastases from carcinoma of the lip are uncom-
mon except in advanced lesions, recurrent lesions, or lesions
arising at the oral commissure. When lymphatic spread
arises from midline lip lesions, bilateral nodal metastases
are more prevalent.
Treatment planning for carcinoma of the buccal mucosa
is similar to that for cancers of the lip. Surgical resection is
recommended for stage I and II tumors, with combination
therapy using surgery and postoperative radiotherapy for
stage III and IV tumors.
Tumors of the alveolar ridge typically present with sore-
ness or gum pain, ulceration, intraoral bleeding, loosening of
teeth, or ill-fitting dentures. Surgery is recommended as the
 Neoplasms of the Oral Cavity and Oropharynx 503

primary treatment modality for early cancers, with the addi-

tion of postoperative radiotherapy for advanced lesions.
Branches from the glossopharyngeal (IX) nerve provide
sensory innervation to the retromolar trigone, so patients with
carcinoma of the retromolar trigone may present complain-
ing of pain referred to the ipsilateral ear. Numbness in the
distribution of the inferior alveolar nerve may be observed if
tumor invades the mandible. Trismus may result from inva-
sion of the pterygoid musculature. Extension into the ptery-
gopalatine fossa may lead to disease at the skull base. The
proximity of the structures of the oropharynx, including the
base of the tongue, soft palate, and tonsil, places them at risk
for tumor involvement by direct extension.
Presenting symptoms of cancer of the hard palate include
pain, bleeding, improper denture fit, or altered speech.
Patients often delay for 3 to 6 months before presenting for
treatment. For early-stage lesions, no differences have been
shown between single-modality treatment using either
surgery or irradiation, so selection of therapy should be based
on the anatomic location and extent of disease, the presence
of second primaries, and associated patient comorbidities.
Surgery followed by adjuvant radiotherapy is recommended
for advanced-stage disease. Regional lymphatic drainage
from the hard palate is sparse, so metastases to cervical
lymph nodes are uncommon.
By virtue of their location, cancers of the floor of the
mouth may remain undetected until progressing to advanced
disease. Large bulky tumors may affect normal speech and
deglutition. Patients may complain of pain referred to the
ipsilateral ear from tumor involvement of the lingual nerve
extending to the main trunk of the mandibular nerve (V3).
Advanced tumors may invade the tongue or mandible by
direct extension. Elective treatment of the neck is warranted
in carcinoma of the floor of the mouth owing to the significant
incidence of occult nodal metastases. The risk of contralateral
504 Otorhinolaryngology

nodal metastases is significant with floor of the mouth cancer,

and multiple levels are often involved. Surgery is recom-
mended for early-stage lesions, whereas combined surgery
and postoperative radiotherapy are the treatment of choice
for advanced floor of the mouth cancers.
Common presenting symptoms and signs for carcinoma
of the oral tongue include localized pain and the presence of
an ulcer, frequently at the middle third of the tongue. Patients
may report dysarthria or pain with eating. As with the floor of
the mouth, cancers of the oral tongue may present with
referred pain in the ipsilateral ear owing to involvement of the
mandibular nerve (V3). Surgical resection is typically
employed for stage I and II lesions, whereas combined ther-
apy using surgery and postoperative radiotherapy is indicated
for stage III and IV disease. Occult metastases in regional
lymphatics are common with carcinoma of the tongue, par-
ticularly when the depth of the primary tumor is greater than
2 mm thick. The risk of regional metastases approaches 40%
in this group of patients, necessitating elective treatment of
the N0 neck with carcinoma of the oral tongue.
The pectoralis major myocutaneous flap provides well-
vascularized soft tissue for reconstructing oral cavity defects
in a single stage. The radial forearm free flap and rectus abdo-
minis free flap are two types of free tissue transfer useful for
intraoral soft tissue reconstuction. Mandibular defects may
be successfully reconstructed with composite bone flaps,
including the fibular osteocutaneous free flap or iliac crest
osteocutaneous free flap.

SPECIFIC SITES IN THE OROPHARYNX

Typical of cancers of the oropharynx, base of the tongue can-
cers often present at an advanced stage of disease. Overall,
62% of patients present with nodal metastases, and con-
tralateral or bilateral nodal involvement is frequently seen.
 Neoplasms of the Oral Cavity and Oropharynx 505

A variety of treatment options for base of the tongue can-

cer have been proposed, including surgery with or without
postoperative radiotherapy, primary external beam radiother-
apy, external beam radiation therapy with brachytherapy
implantation with or without neck dissection, and induction
chemotherapy with external beam radiation therapy with or
without brachytherapy.
For cancers of the soft palate, either surgery or radiother-
apy provides good local control and survival rates in early-
stage (stages I and II) tumors. Combination therapy, using
surgical resection followed by adjuvant radiation therapy, is
recommended for stage III and IV tumors.
Of all of the tumors in the oral cavity and oropharynx,
cancers of the tonsil are the most radiosensitive, particularly
exophytic lesions. Stage I and II tumors may be best
approached with primary radiotherapy, recognizing the
potential for occult nodal metastases. Treatment planning for
stage III and IV tumors is slightly more complicated as the
method of choice may differ depending on the particular
situation. A small tonsil primary with extensive nodal metas-
tases may be treated with primary radiotherapy with consid-
eration for neck dissection. In contrast, a large primary tumor
at the tonsillar region without regional lymph node metas-
tases could be approached with combination surgery and
postoperative radiotherapy or with combination chemother-
apy and irradiation.
Cancers of the posterior pharyngeal wall commonly pre-
sent with dysphagia and odynophagia. Alternatively, the patient
may complain of a globus sensation or change in voice. Both
surgery and radiation have been singly employed, often with
disappointing results. Although the data are sparse, it appears
that combination therapy of surgery and postoperative radio-
therapy may be indicated, particularly for advanced disease.
Advanced lesions of the oropharynx necessitating a
mandibulotomy approach with mandibular preservation may
506 Otorhinolaryngology

require flap reconstruction to resurface the inner portion of

the mandible. The thin, pliable nature of the radial forearm
free flap makes it a preferable choice over the pectoralis
major myocutaneous flap for reconstruction in this region