21/7/2021 Cancer of the Oropharynx: Risk Factors, Diagnosis, Treatment, and Outcomes - American Head & Neck Society

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PUBLISHED ON JANUARY 21, 2016 BY JJ JACKMAN

AHNS MEETINGS
Cancer of the Oropharynx: Risk Factors,
Diagnosis, Treatment, and Outcomes
Authored by Charles Coffey, MD & Tamer Ghanem, MD PhD; edited by Ellie Maghami, MD FACS

AHNS Education Committee

Introduction
This document is intended to introduce a subtype of head and neck cancer known as oropharynx
cancer, and the normal anatomy and physiology of the oropharynx will be reviewed. Factors that
can lead to cancer formation in this area are defined. Information regarding diagnosis, treatment,
and expected outcomes of this condition is provided. WEBINAR CALENDAR

Anatomy & Functional Considerations

The oropharynx is the middle compartment of the pharynx,  i.e. throat; it is the region of the throat
between the nasopharynx (top compartment) and hypopharynx (bottom compartment). The
oropharynx includes the tonsils, tongue base, soft palate, and pharyngeal walls. Several of these
subsites are very common locations for the development of head and neck cancer, and a tumor AHNS CALL FOR
present in any of these subsites can be broadly categorized as an oropharyngeal tumor. It is ABSTRACTS
important to distinguish the oropharynx from the oral cavity (mouth), as tumors arising in these
two sites may behave differently and require very different considerations regarding function and
appropriate treatment.

The tonsils (also referred to as palatine tonsils) are collections of lymphoid tissue located on each
side of the oropharynx which participate in the immune function of the aerodigestive tract.
Although tonsils may be quite large during childhood, they generally regress with age, and many
adults have very little visible tonsillar tissue remaining. Enlargement or asymmetry of the tonsils
in an adult may simply be an anatomic variant, but may also be an indication of tumor presence.
Removal of tonsils has not been found to compromise immune status.

The base of tongue (or tongue base) refers to the portion of the tongue which resides in the
oropharynx (posterior 1/3 of the tongue). The base of tongue is functionally and anatomically AHNS
distinct from the oral tongue, which is the portion of the tongue which resides in the oral cavity ANNOUNCEMENTS
(anterior 2/3 of the tongue) and is most important for speech and language. The muscles of the
base of tongue are more involved with swallowing than speech, and play a critical role in
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controlling the passage of food and liquids from the mouth into the throat. Base of tongue
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dysfunction resulting from tumor, loss of tissue due to surgery, or radiation-related effects may
result in difficulty swallowing or aspiration (spillage of liquids into the larynx or voicebox).  Congratulations to the 2018
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The soft palate is a muscular soft tissue sling which resides behind the hard palate, or roof of the
mouth. The soft palate separates the nose and nasopharynx from the remainder of the pharynx
and oral cavity during speech and swallowing. Inability to close the soft palate (velopharyngeal
insufficiency) due to tumor, resection, or scar may result in hypernasal speech as well as reflux of

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21/7/2021 Cancer of the Oropharynx: Risk Factors, Diagnosis, Treatment, and Outcomes - American Head & Neck Society

liquids into the nose during swallowing.  The lateral and posterior walls of the oropharynx are
comprised primarily of muscles which play a supporting role in the pharyngeal phase of
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swallowing.

American Head …
Epidemiology 2.8K likes

The oropharynx is one of the most common sites of head and neck cancer in the United States. It is
estimated that 11,000-13,000 new cases of oropharyngeal cancer are diagnosed in the United
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States each year (Jemal; Siegel; CDC). The vast majority of these tumors are squamous cell
carcinoma, a cancer which arises from squamous epithelial cells which line the upper aerodigestive
tract.  Squamous cell carcinomas may also arise at numerous other sites including the skin, lungs,
bladder, and cervix, but tumor behavior and treatment options vary greatly across different body
sites.  Males are more than four times as likely as females to develop oropharyngeal squamous cell
carcinoma (OPSCC), with an overall annual risk of 6.2 per 100,000 men compared to 1.4 cases per
100,000 women (Jemal, CDC). Incidence in the U.S. is highest among white and black men, and
lower among Hispanics, Native Americans and Asians/ Pacific Islanders.

Risk Factors
Tobacco and Alcohol

Tobacco use has been strongly established as the primary risk factor in the majority of head and
neck aerodigestive tract cancers (Sturgis 04, Sturgis 07). Lifetime risk of developing head and neck
cancer is increased 10-fold in smokers, and the magnitude of risk increases up to 25-fold for the
heaviest smokers. Alcohol use is an independent risk factor for development of head and neck
cancer. Although the risk is higher with chronic heavy alcohol use, there is some evidence that
light alcohol use may also increase risk of developing oropharyngeal cancer (Bagnardi). Combined
use of both tobacco and alcohol further increase cancer risk (Masberg). Historically, up to 90% of
head and neck squamous cell carcinoma including OPSCC has been attributed to tobacco use and
alcohol abuse (Sturgis 04). Tobacco use in the United States has been steadily declining for the last
five decades, with the percentage of active smokers decreasing from 43% in 1965 to below 20% in
2010 (Mariolis, Skinner). Per capita alcohol use has shown a more modest decline, from 2.7 gallons
per year in the mid-1980s to 2.26 gallons per year in 2010 (LaVallee). These trends have generally
been paralleled by decreasing rates of head and neck cancer incidence and mortality.

Human Papilloma Virus

Despite decreasing rates of tobacco and alcohol use, the rates of oropharyngeal cancer have
trended steadily upward for the last decade. This is primarily due to the increase in cancers
related to infection with the human papilloma virus (HPV). Human papilloma viruses are a large
group of related viruses which are spread through vaginal, oral and anal sex. HPV is the most
common sexually transmitted infection in the United States, affecting more than half of sexually
active individuals at some point during their lives (NCI). Several strains of HPV are associated with
increased risk of developing cervical, genital, and oropharyngeal cancers. Infection of epithelial
cells by high-risk strains of HPV is associated with production of viral proteins which may
eventually interfere with the cell’s normal ability to suppress tumor growth. The immune system
successfully eliminates HPV infection in most patients, and only a small portion of patients
infected with high-risk HPV strains will develop an HPV-related cancer.  It is estimated that
approximately 7% of those aged 14 to 69 years in the U.S. have oral HPV infection at any one time,
as detected by an oral rinse.  Approximately half (3.7%) of those infections are with high-risk HPV
strains (Gillison 2012; Sanders). The time lag between an oral HPV infection and the development
of HPV-related oropharyngeal cancer is estimated at between 15 and 30 years. As such, the rise in
OPSCC seen since the 1990s in large part reflects changes in sexual practices in the 1960s and
1970s.

The risk profile for HPV-related OPSCC differs from most head and neck cancers. When
compared to patients with non-HPV tumors, patients with HPV-positive OPSCC are more likely to
be young, white, higher socioeconomic status, non-smokers, and non-drinkers. Sexual history is
strongly associated with HPV-positive cancers. Significant increase in risk of OPSCC has been
associated with lifetime number of sexual partners, any history of oral sex, earlier age at sexual
debut, infrequent use of barrier devices during sex, lifetime history of sexually transmitted
disease, and, among men, with a history of same-sex sexual contact (Heck; Gillison 2008).

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An association between head and neck cancer and marijuana use has been demonstrated, but it
remains uncertain whether marijuana use is an independent risk factor for OPSCC (Gillison 2008).
Poor oral health, including periodontal disease and tooth loss, has been implicated in the etiology
of oral and oropharyngeal carcinoma, but the associations have been modest and the evidence has
generally been inconclusive (Divaris). High dietary intake of fruit and vegetables may be
somewhat protective for oral and pharyngeal cancer, though the evidence for this has not been
conclusive (Lucenteforte).

Diagnosis & Evaluation

Any patient with a persistent mass of the neck or throat or with symptoms suggesting
oropharygneal cancer should be referred to an otolaryngologist (ENT) or head and neck surgeon
for further evaluation. Symptoms of oropharyngeal cancer may include throat pain, difficulty
swallowing, weight loss, ear ache, voice change, and blood-tinged saliva. Initial evaluation consists
of a detailed medical history and comprehensive head and neck examination, generally including
examination of the pharynx and larynx with a small flexible endoscope performed in an office
setting. Any suspicious tumors of the oropharynx should be biopsied for histopathologic
evaluation. In many instances it is possible to perform biopsy in clinic if a lesion is easily accessible
either directly through the mouth or via flexible endoscopy. However, in many instances
evaluation will require additional examination and biopsy under general anesthesia in an
operating room.  Such procedures can generally be completed in less than thirty minutes and may
be performed on an outpatient basis in most instances.  In certain circumstances, it is possible to
obtain adequate tissue for diagnosis via a needle biopsy (fine needle aspiration, or FNA) if a lymph
node within the neck has become involved with cancer (i.e. a nodal metastasis).  Needle biopsy is
most often perfomed in clinic and does not require anesthesia, although it may not provide the
same degree of staging information as examination under anesthesia. Testing of biopsy specimens
for HPV status is recommended in all cases. HPV-positive status predicts better outcomes with
standard therapies in general, but this information should not currently be used to tailor decisions
regarding treatment with the exception of carefully monitored clinical trials..

All patients with a confirmed diagnosis of OPSCC should undergo evaluation by a multidisciplinary
treatment team. Imaging should be obtained to evaluate the primary tumor, involvement of lymph
nodes in the neck, and for evidence of metastatic cancer spread beyond the head and neck.
Providers may choose to order either computed tomography (CT scan) or magnetic resonance
imaging (MRI) of the neck to evaluate the pharynx and lymph nodes in the neck. This scan should
be performed with IV contrast in nearly all cases, with the exception of patients with impaired
kidney function or an allergy to contrast dye. CT scan of the chest is also indicated in most cases,
to evaluate for the presence of metastatic cancer in the lungs or lymph nodes of the chest. 
Positron emission tomography (PET scan) is also being used with increased frequency for
pretreatment evaluation, particularly for patients with advanced-stage disease.

As part of the pretreatment evaluation, all patients who elect to pursue radiation therapy should
undergo dental evaluation prior to treatment.  As a result of the effects of radiation on bone and
surrounding tissue, there is a significantly increased risk of bone-related complications associated
with dental procedures which are performed following radiation therapy. In the most severe
instances, dental extraction or infection after radiation may result in death of bone tissue
(osteoradionecrosis) requiring surgical removal of bone. To minimize the risk of these complications,
tooth extractions prior to radiation may be recommended if there is evidence of dental decay or
advanced periodontal disease. Pretreatment nutrition and speech and swallowing evaluations
should be provided to all patients. Patients experiencing significant weight loss or swallowing
difficulty as a result of OPSCC may benefit from surgical placement of a feeding tube into the
stomach prior to treatment. However, many patients are able to maintain an oral diet throughout
the duration of treatment, and feeding tube placement is not required for all patients. Whenever
possible, patients undergoing treatment for OPSCC should continue to eat and drink by mouth
during the course of treatment, as long as this is approved as safe by the treatment team.
Exercising pharyngeal muscles during treatment can help maintain normal swallowing function
both throughout and after cancer therapy.

In a small subset of patients squamous cell cancer is diagnosed only by needle aspiration biopsy of
an abnormally enlarged lymph node. In these instances physical exam, imaging and intraoperative
biopsies may fail to reveal an obvious cancer in the throat. These cases are referred to as
“unknown primary” as the site of primary cancer development remains hidden. In these instances

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it is particularly recommended that the needle aspirate be tested for HPV. HPV-positive status
suggests oropharynx as the most likely site for cancer origin and predicts improved outcomes.

Staging

(AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th
ed. New York, NY: Springer, 2010, pp 41-56)

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