HEAD AND NECK CANCERS
SALEEM A KHANANI
ANATOMY
ANATOMY
PATHOLOGY
1.
2.
3.
4.
5.
6.
7.
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
