HEAD AND NECK CANCERS

SALEEM A KHANANI

ANATOMY

ANATOMY

PATHOLOGY
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Squamous cell carcinoma

Nasopharyngeal carcinoma
Salivary gland: adenocarcinoma, acinic cell,
adenoid cystic, mucoepidermoid, benign mixed
Paranasal sinus: esthesioneuroblastoma, primary
neuroendocrine tumor
Lymphoma, plasmacytoma
Thyroid cancers
Sarcoma, melanoma, metastatic cancers

Natural history
Late presentation
Local extension major cause of morbidity
Nodal spread common
Multiple aerodigestive cancers (10-30%)
Distant metastases uncommon (10-20%)

-lung, bone

EPIDEMIOLOGY
3% of all malignancies
550,000 new cases per year in US. 12000 deaths
8400 may be caused by HPV
Median age of diagnosis: ~60 years
Male>Female
Strongly associated with tobacco and alcohol
Epstein-Barr virus risk factor for nasopharynx cancers
Human papillomavirus increasingly appreciated as a
risk factor

SMOKING AND CANCER

5 to 25 fold increased risk in smokers
Dose response relationship
Case controlled study showed
The relative risk (RR) in current tobacco users was 6.5. The

RR increased with the duration of smoking and gradually

declined after smoking cessation with no excess risk at 20
years.
The age of starting smoking (below 18 years of age) and
duration of smoking (over 35 years) were high-risk factors.
Cessation of smoking was associated with a significant
decrease in relative risk

Smoking and cancer

Both cigar and pipe smoking are also associated with

an increased incidence of head and neck cancer, and

this increase in risk is present even in those who
have never smoked cigarettes . Smokeless tobacco
(both chewing tobacco and snuff) is associated with
an increased risk of cancer of the oral cavity and
pharynx [
Secondhand smoke exposure may be a contributing
factor, primarily in women and those with tongue
cancer.

Alcohol and cancer

Intake greater than 50 g/day versus less than 10

g/day (one drink contains approximately 12 g of

alcohol). Alcohol intake and tobacco smoking appear
to have an interactive and multiplicative effect on the
risk of developing head and neck cancer.
There may be an interaction of genetic susceptibility
and alcohol intake on the risk of developing head
and neck cancer with genetic polymorphisms of
alcohol dehydrogenase (ADH) and aldehyde
dehydrogenase (ALDH)

Other factors
Betel nut chewing
Formaldehyde: classified as a carcinogen 2004

associated with nasopharyngeal cancer and possibly

cancers of nasal cavity and paransal sinuses.
Agent orange: larynx and base of tongue
Multiple other chemicals
Post radiation: long latency period. Low risk
thyroid cancer, salivary gland tumors, squamous
cell cancers, and sarcomas

Diet and cancer

Protective effect: increased consumption of fruits

and vegetables
Increased risk of nasopharyngeal CA:
in frequent consumers of preserved meats
contain high levels of added nitrites

that

Genetic factors and pathways

Metabolic polymorphisms: associated with

carcinogens in tobacco smoke

DNA repair gene polymorphisms
Fanconi anemia

Viruses and cancer

A large body of evidence supports the role of EBV as the

primary etiologic agent in the pathogenesis of

nasopharyngeal carcinoma.
EBV is the primary etiologic agent for oral hairy
leukoplakia. A possible relationship of oral hairy
leukoplakia to squamous cell carcinoma is uncertain
There is an approximately two- to threefold increase in
the incidence of squamous cell carcinoma of the head
and neck in HIV-infected patients
HSV: less strongly correlated. Higher levels of IgM
antibody to HSV type one than control subjects

HPV ASSOCIATED CANCERS

> 99% of Cervical Carcinoma
~ 90% Anal Carcinomas
~ 40% Vulvar and Vaginal Carcinomas
~ 60% of Oropharynx Cancers
~ 200 HPV types
~ 30 Mucosal HPVs
Low-Risk: Genital Warts (Types 6 and 11)
High-Risk: Lesions That Progress to Cancer (Types

16 and 18; others 31, 35, 39, 45, 51, 52, 58)

HPV POSITIVE HEAD AND NECK CANCER

HPV 16 is the viral subtype in the vast majority of
patients.
7% of people have oral HPV; 1% have HPV 16.
Half of oropharynx cancers will have HPV 16 DNA.
Often occurs in nonsmokers, nondrinkers
Median age younger than HPV-negative patients;
incidence increasing
Men and women at more similar risk.
Associated with number of sexual partners and high risk
sexual practices
Favorable prognosis

HPV TESTING IN TUMORS

In situ hybridization
p16 immunohistochemistry
PCR

TWO DISTINCT HNSCC ENTITIES

Chemoprevention: Rationale
Field cancerization Patients with carcinogen
related head and neck cancer have a predilection for
cancer development throughout the oral and
oropharyngeal mucosa. Whether this is also true for
HPV associated oropharyngeal tumors is not clear.
Multistep carcinogenesis Squamous cell cancers of
the head and neck result from a multistep process with
defined intermediate stages, leading to fully
transformed, invasive, and metastatic cancer

Chemoprevention
No chemopreventive agents have been shown to

decrease the incidence of squamous cell carcinoma

of the head and neck in adequately powered
randomized clinical trials.

Some of the strategies

Standard options for managing oral dysplasia, a

precursor of invasive cancer, range from watchful

waiting to biopsy, laser surgery and aggressive
resection. However, none of these approaches is of
clear clinical benefit
Avoidance of further known carcinogenic exposures
(eg, tobacco and alcohol)
Primary vs secondary prevention
Screening of high risk individuals based upon risk
factors and/or premalignant lesions.

Prevention of HPV associated cancer

No FDA approved test to diagnosed HPV in the

mouth or throat
Use of condoms and dental dams during oral sex?
No approved vaccine for prevention of head and
cancer as yet

Screening
Accessible to physical examination by physicians,

dentists, oral surgeons, hygienists

60% of US population sees a dentist every year.
Less than 25% of those who visit a dentist regularly report
having had an oral cancer
Emphasis on routine mouth examination in high-risk
individuals
Anti-tobacco health education
Whether or not any of these strategies are cost-effective is
not known. Currently, there is no effective oral cancer
screening program.

Screening guidelines
American Dental Association recommends all adults

undergo periodic oral exams when they visit the dentist.

The American Cancer Society recommends discussing
oral cancer screening with patients
. The U.S. Preventive Services Task Force (USPSTF)
concludes that there is insufficient evidence either for or
against routine oral cancer screening in adults.
The USPSTF also says that techniques other than the
standard oral exam are being evaluated but are still
experimental.

PREVENTION AND SCREENING

Premalignant lesions: Leukoplakia and Erythroplakia

The prevalence of premalignant oral lesions is

approximately 1%-5%.[6] Overall, the rates of oral

squamous dysplasia and subsequent squamous cell
carcinoma (SCC) are decreasing, closely paralleling the
decrease in cigarette smoking.
Most cases are seen in adults older than 50 years with risk
factors, with a male-to-female ratio of approximately 3:1;
this difference becomes more pronounced with increasing
age. However, recent evidence has showed that the ratio
has decreased, believed to have resulted from a relative
increase of cigarette smoking among women

PREMALIGNANT LESIONS

Leucoplakia
Leucoplakia: Irregular, smooth to thickened leukoplakia
involves the dorsal, lateral, and dorsal surfaces of the tongue,
which demonstrated no sign of dysplasia in multiple areas of
incisional biopsy

Erythroplakia
Erythroplakia is characterized by a smooth, velvety
clinical presentation with a homogeneous surface,
without ulceration.

SITES OF ORAL CANCER

TONGUE
LIP
FLOOR OF THE MOUTH
BUCCAL MUCOSA
GUMS
PALATE

CLINICAL FEATURES
Lump
Soreness
Thickening in the soft tissues
Difficulty chewing
Difficulty swallowing
Difficulty moving the jaw or tongue
Hoarseness
Numbness in the tongue or other areas of the mouth
Ill fitting dentures
White or red patch
Neck lump
Earache
Weight loss

When to do more?
Any sore, discoloration, induration, prominent
(exophytic) tissue, irritation, hoarseness, complaints of
difficulty in swallowing, unilateral earaches, which
does not resolve within a two week period on its own,
with or without treatment, should be considered
suspect and worthy of further examination or referral.

Lesions mimicking cancer

Herpes simplex ulceration
Aphthous ulcerations
Resolve within 10 to 14 days
"an atypical herpetic/aphthous lesion. Often turn out

to be squamous cell cancer

Diagnosis
Brush cytology
Any positive found through brush cytology, must be

confirmed by conventional incisional or punch

biopsy.
Lymph node biopsy
FNA of palpable lymph node

LYMPH NODE LEVELS

Level I: Submental and submandibular nodes
Level Ia: Submental triangle
Level Ib: Submandibular triangle
Level II: Upper jugular nodes
Level III: Middle jugular nodes
Level IV: Lower jugular nodes
Level V: Posterior triangle group
Level VI: Anterior triangle group

LYMPHATIC DRAINAGE
Each anatomic site has a predilection for spreading
to different lymph node level.
I: Oral cavity
II/III/IV: Larynx/pharynx
II/V: Nasopharynx
V: Scalp
III/IV/V: Thyroid
IV/V: Below the clavicles

EVALUATION AND STAGING

STAGING

SURVIVAL ACCORDING TO STAGE

TREATMENT: GENERAL PRINCIPLES

TREATMENT: GENERAL PRINCIPLES

TREATMENT APPROACH