Head and Neck Cancer The concept of head and neck cancer is included in the syllabus of the master's of clinical pharmacy.This presentation includes epidemiology, Types, Pathology, Etiology and risk factors, signs and symptoms, treatment according to stages, Classification, Mechanism of action, and the latest research.

1. HEAD AND NECK
CANCER
By
Miss. Shruti Rajendra
Rudraksha
Department of
Clinical Pharmacy
M. Pharm First year
Guide
Dr. S. D. Patil

2. What exactly head and neck cancer
means?
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Head & neck cancer refers to cancers of the UADT (Upper aero digestive
tract)
1. Oral Cavity
2. Pharynx
3. Larynx
4. Nasal cavity & Paranasal sinuses
5. Salivary glands

3. EPIDEMIOLOGY
• Overall, head and neck cancer accounts for more than 550,000 cases
annually worldwide.
• Males are affected significantly more than females with a ratio ranging
from 2:1 to 4:1.
• The incidence rate in males exceeds 20 per 100,000 in India.
• Head and neck cancers are common in India and account for about 30%
of cancers in males and about 13% in females.
• Oral cavity cancers are more common in the India.
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4. HEAD AND NECK CLASSIFICATION
Head and neck cancers arise from a variety of locations and structures within
the head and neck region.
This region is divided into five sites by which cancers are classified
1. Oral cavity, which includes the lips, buccal mucosa, anterior tongue, floor
of the mouth, hard palate, upper gingiva, lower gingiva, and retromolar
trigone.
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6. 2. Pharynx which is divided into the nasopharynx, the oropharynx, and the
hypopharynx.
The nasopharynx, the narrow tubular passage behind the nasal cavity, is the upper
part of the pharynx.
The oropharynx, the middle part of the pharynx, includes the tonsillar area, the
tongue base, the soft palate, and the posterior pharyngeal wall.
The hypopharynx, which is the lower part of the pharynx, includes the pyriform
sinuses, the posterior surface of the larynx (post cricoid area) and the infer
posterior, and inferolateral pharyngeal wall.
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8. 3. Larynx is divided into three anatomic regions the supraglottic larynx, the
glottic larynx (true vocal cords and the anterior and posterior commissures)
and the subglottic larynx.
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9. 4. Nasal cavity and the paranasal sinuses, which include the maxillary,
ethmoid, sphenoid, and frontal sinuses
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10. 5. Major salivary glands (parotid, submandibular, and sublingual) and the
minor salivary glands, which are located throughout the submucosa of the
mouth and upper aerodigestive tract.
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11. • Squamous cell carcinomas account for 90 to 95 percent of the lesions in
the head and neck.
• They can be categorized as well differentiated (greater than 75 percent
keratinization), moderately differentiated (25 to 75 percent keratinization),
and poorly differentiated (less than 25 percent keratinization) tumors.
• Less common histologies include verrucous carcinoma (a variant of
squamous cell carcinoma), adenocarcinoma, adenoid cystic carcinoma, and
mucoepidermoid carcinomas
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PATHOLOGY

12. 1. Smoking : In heavy cigarette smokers, there is a 5- to 25-fold increased risk
of cancer compared with nonsmokers.
2. Alcohol : Alcohol consumption independently increases the risk of cancer in
the upper aerodigestive tract.
3. Viral infection Epstein-Barr virus : A large body of evidence supports the role
of EBV as the primary etiologic agent in the pathogenesis of nasopharyngeal
carcinoma.
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ETIOLOGY AND RISK FACTORS

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4. Human papillomavirus –Sexual activity with a person who has HPV is the
most common way someone gets HPV. Particularly those arising in the base of
the tongue and the tonsils. HPV associated oropharyngeal cancers are typically
seen in younger men who are non users of tobacco and alcohol.
6. Human immunodeficiency virus —There is an approximately two- to three
fold increase in the incidence of squamous cell carcinoma of the head and
neck in HIV-infected patients.

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6. Genetic factors — Multiple genetic
factors and pathways may contribute to an
increase in risk of head and neck cancer,
and these factors may interact with other
known risk factors.
Two inherited genetic syndromes, Fanconi
anemia and Dyskeratosis congenita, may
greatly increase the likelihood of developing
throat and mouth cancers in people at an
early age.
Fanconi
anemia
Dyskeratosis
congenita

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7. Radiation — Prior irradiation for either malignant or benign disease has
been linked to thyroid cancer, salivary gland tumors, squamous cell cancers,
and sarcomas.
8. Diet- Several studies have shown a protective effect associated with
increased consumption of fruits and vegetables. Studies suggest that the risk
of nasopharyngeal carcinoma is increased in frequent consumers of
preserved meats that contain high levels of added nitrites

16. 9. Age- People over the age of 40 are at higher risk for head and neck cancer.
10. Marijuana use
11. Poor nutrition- A diet low in vitamin A and B can raise a persons risk.
12. Weakened immune system.
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17. SIGNS AND SYMPTOMS
• Swelling or a sore that does not heal; this is the most common symptom
• Red or white patch in the mouth
• Lump, bump, or mass in the head or neck area, with or without pain
• Persistent sore throat
• Foul mouth odour not explained by hygiene
• change in voice
• Nasal obstruction or persistent nasal congestion
• Frequent nose bleeds and/or unusual nasal discharge
• Difficulty breathing
• Double vision
• Numbness or weakness of a body part in the head and neck region
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18. DIAGNOSIS
• Physical examination/blood and urine tests. During a physical examination, the doctor
feels for any lumps on the neck, lips, gums, and cheeks. The doctor will also inspect the
nose, mouth, throat, and tongue for abnormalities, often using a light and a mirror for a
clearer view. Blood and urine tests may be done to help diagnose cancer.
• Endoscopy. It allows the doctor to see inside the body with a thin, lighted, flexible tube
called an endoscope. The person may be sedated as the tube is gently inserted through
the nose into the throat and down the esophagus to examine inside the head and neck.
Sedation is giving a person medication to become more relaxed, calm, or sleepy.
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19. • Panoramic radiograph. A panoramic radiograph is a rotating, or panoramic, x-ray
of the upper and lower jawbones to detect cancer or evaluate the teeth before
radiation therapy or chemotherapy. This is often called a Panorex.
• Ultrasound. An ultrasound uses sound waves to create a picture of internal
organs.
• Molecular testing of the tumor. Your doctor may recommend running laboratory
tests on a tumor sample to identify specific genes, proteins, and other factors
unique to the tumor. Results of these tests can help determine your treatment
options.
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20. IMAGING STUDIES
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1. Fine needle aspiration cytology — Fine needle
aspiration cytology (FNA) is frequently used to make an
initial tissue diagnosis of a head and neck cancer when a
patient presents with a neck mass (metastatic cervical
lymph node) without an obvious primary mucosal/upper
aerodigestive tract site.
This technique has high sensitivity and specificity and a
diagnostic accuracy that ranges from 89 to 98 percent .

21. • Imaging studies (computed
tomography [CT], magnetic
resonance imaging [MRI], positron
emission tomography [PET], and
integrated PET/CT) are important
for assessing the degree of local
infiltration, involvement of regional
lymph nodes, and presence of
distant metastases or second
primary tumors.
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22. TNM staging system
• Tumor (T): How large is the primary tumor? Where is it located?
• Node (N): Has the tumor spread to the lymph nodes? If so, where and
how many?
• Metastasis (M): Has the cancer spread to other parts of the body? If so,
where and how much?
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23. 1. EARLY STAGE - Approximately 30 to 40 percent of patients with head and neck
squamous cell carcinomas (HNSCCs) present with early (stage I and II) disease. In
general, these patients are treated with either primary surgery or definitive radiation
therapy (RT).
2. ADVANCED STAGE - Historically, local therapy alone, i.e, primary surgery or definitive
radiation therapy (RT), for locoregionally advanced (stage III, IVA, and IVB) head and
neck squamous cell carcinomas resulted in high rates including loss of tongue and
larynx function (speech and swallowing).
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TREATMENT ACCORDING TO STAGES

24. TYPES OF TREATMENT
• Medical oncologist: A doctor who treats cancer using medications, such as
chemotherapy, immunotherapy, and targeted therapy.
• Radiation oncologist: A doctor who specializes in treating cancer using radiation
therapy.
• Surgical oncologist: A doctor who treats cancer using an operation.
• Reconstructive/plastic surgeon: A doctor who specializes in reconstructive surgery,
which is done to help repair damage caused by cancer treatment.
• Maxillofacial prosthodontist: A specialist who performs restorative surgery in the head
and neck areas.
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25. CLASSIFICATION OF CHEMOTHERAPEUTIC AGENT
1. ALKYLATING AGENTS- Cisplatin, Carboplatin, Oxaliplatin
2. ANTIMETABOLITES- 5- fluorouracil
3. ANTITUMOR ANTIBIOTICS - Actinomycin D, Bleomycin, Daunorubicin,
Doxorubicin
4. TOPOISOMERASE INHIBITORS- Etoposide, Irinotecan
5. MITOTIC SPINDLE AGENTS –Paclitaxel, Docetaxel, Vinblastine, Vincristine,
Vinorelbine
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26. 6. TYROSIN KINASE INHIBITORS- CYP34A inhibitors and inducers, Imatinib,
Masitinib, Erlotinib, Gefitinib, Lapatinib
7. MONOCLONAL ANTIBODIES –Cetuximab, Panitumumab, Rituximab
8. HORMONAL AGENTS –Adrenocorticoids, Adrenal inhibitors: mitotane,
Androgens, Antiandrogens, Aromatase inhibitors, LHRH agents Progestins.
9. CYTOPROTECTIVE AGENTS- Dexrazoxane
10. MISCELLANEOUS AGENTS-Interferon, Interleukins, Lenalidomide,
Retinoic acid receptor inhibitor
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27. CHEMOTHERAPEUTIC AGENTS COMMONLY
EMPLOYED FOR HNCs
• Cisplatin
• Carboplatin
• 5-Fluorouracil
• Methotrexate
• Bleomycin
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• Toxoids
• Vinca alkaloids
• Monoclonal antibodies
• Tyrosine kinase inhibitors

28. ALKYLATING AGENTS- Cisplatin
• Cisplatin binds to the N7 reactive center on purine residues and as such can cause
deoxyribonucleic acid (DNA) damage in cancer cells, blocking cell division and resulting
in apoptotic cell death. The 1,2-intrastrand cross-links of purine bases with cisplatin are
the most notable among the changes in DNA
• Acute toxicity: Chiefly nausea and vomiting- managed by premedication with emetics.
• Delayed toxicity: Nephrotoxicity , ototoxicity , peripheral sensory neuropathy, Nerve
dysfunction and hypersensitivity reaction.
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29. ANTIMETABOLITE- Methotrexate
• Two most common antimetabolites commonly employed in HNCs are Methotrexate and
5-fluoro Uracil.
• MTX- folic acid antagonist that binds to the active catalytic site of DHFR interfering-
interrupts the de novo synthesis of thymidylate, purine nucleotides, and the amino
acids serine and methionine- interfering with the formation of DNA, RNA, and key
cellular proteins.
• 5-FluoroUracil: 5-FU acts principally as a thymidylate synthase (TS) inhibitor –blocks
thymine synthesis. inhibits DNA replication- thymine less death.
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30. ANTITUMOR ANTIBIOTICS -Bleomycin
• MOA: acts by binding to DNA- single-strand and double-strand breaks
following free radical formation- inhibition of DNA biosynthesis.
• Acute Toxicity: Allergic reactions, fever, hypotension.
• Delayed Toxicity: Almost every patient experience fever - first 4-12hrs
after bleomycin injection-usually brief and not clinically troublesome. Skin
toxicity common - toxic free radicals producing DNA damage: -managed
by topical steroids
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31. MITOTIC SPINDLE AGENTS- Paclitaxel
• Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome
segregation, and cell division. Chromosomes are thus unable to achieve
a metaphase spindle configuration. This blocks the progression of mitosis and prolonged
activation of the mitotic checkpoint triggers apoptosis or reversion to the G0-phase of the
cell cycle without cell division.
• Acute toxicity: Nausea, vomiting, hypotension, arrhythmias, and hypersensitivity
reactions-5% of patients within first 2-3 minutes after first or second dose mitosis.
• Delayed toxicity: Peripheral sensory neuropathy is seen which is dose- and time-
dependent59 .Bone marrow depression.
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32. TYROSIN KINASE INHIBITORS- Imatinib
• MOA: Imatinib works by binding close to the ATP binding site of bcr-abl, locking it in a
closed or self-inhibited conformation, and therefore inhibiting the enzyme activity of the
protein semi-competitively.
• Toxicity: generally very well tolerated. side effects such as edema, nausea, rash and
musculoskeletal pain are common but mild.
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33. LATEST RESEARCH
• Immunotherapy. An active area of immunotherapy research is focused on drugs that
block a protein called PD-1. PD-1 is found on the surface of T cells, which are a type
of white blood cell that helps the body’s immune system fight disease. Because PD-1
keeps the immune system from destroying cancer cells, stopping PD-1 from working
allows the immune system to better eliminate the disease. There are 2
immunotherapy drugs approved for the treatment of metastatic or recurrent head
and neck cancers. Researchers are studying PD-1 immunotherapy for people with
recurrent and metastatic head and neck cancer in clinical trials.
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34. • Radiofrequency thermal ablation (RFA). RFA is a minimally invasive treatment option
that applies heat to the tumor to destroy cancer cells. It is usually used to treat a
localized tumor that cannot be removed by surgery.
• Photodynamic therapy. In photodynamic therapy, a light-sensitive substance is injected
into the tumor that stays longer in cancer cells than in healthy cells. A laser is then
directed at the tumor to destroy the cancer cells. The long-term effects of
photodynamic therapy are still being studied.
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