Introduction to Oncology & Oral Squamous Cell Carcinoma

Introduction to Oncology with an Emphasis on Oral Squamous Cell Carcinoma

• Oncology studies tumors with Dr. John AG Buchanan
• This lecture links to other lectures: Upper/Lower GI, Dermatology, Hematology/leukaemias, and Lung Carcinoma

Learning Outcomes

• Broad knowledge of oncology and its nomenclature
• Familiarity with carcinogens associated with specific cancers
• Knowledge of cancer screening methods
• Ability to recall clinical features of common cancers
• Solid understanding of signs, symptoms, and oral cancer classification
• Understanding the role of radiotherapy, chemotherapy, palliative and terminal care in oral cancer management

Definitions

• Oncology studies tumors
• Tumors are abnormal tissue masses with autonomous growth exceeding normal tissue growth
• Unlike non-neoplastic proliferations, tumor growth doesn't stop even after the initial stimulus is removed
• Tumors can be classified as benign or malignant

Nomenclature

• Tumors contain neoplastic cells and supporting stroma like connective tissue and blood vessels
• Tumor names end with "-oma"
• Benign tumor examples include lipoma, fibroma, osteoma, leiomyoma, adenoma, papillomas

Benign Tumors

• Benign tumors stay in their starting place and don't spread to other areas
• They don't spread locally or distantly
• They grow slowly with clear borders
• They can grow and press on structures nearby
• They usually don't come back after being removed
• Some benign tumor examples are colonic polyps

Malignant Tumors

• Malignant tumor's are often called cancers and fall into two main groups
• Carcinomas start in epithelial tissue; an example is oral squamous cell carcinoma
• Sarcomas start in mesenchymal tissue; examples include osteosarcoma and liposarcoma

Malignant Behavior

• Distinction is based on appearance which is (Morphology)
• Distinction is also based on behavior (Clinical course)
• Altered differentiation and anaplasia means cells don't mature normally and lose their shape
• Rapid growth rate is typical
• Invasion of basement membrane occurs eg OSCC, spreading into deeper connective tissue
• Metastasis, or spreading, is the major sign of malignant tumors

Metastasis

• Metastasis means all malignant tumors metastasise except tumors of the brain and Basal cell carcinoma
• Tumors spread through body cavities, lymphatics, and blood vessels (haematogenous)
• Bone and soft tissue tumor (sarcomas) primarily spread through blood
• Melanoma, breast, lung, and gastrointestinal tumors spread through lymph
• Transcoelomic spread is rare, limited to mesotheliomas and ovarian carcinomas

Epidemiology

• Lung cancer is most common cancer worldwide, with 13% of new cases in 2012
• Breast cancer follows, with near 1.7 million new cases in 2012
• Colorectal cancer ranks third at 1.4 million new cases in 2012
• Breast cancer is most common cancer in women worldwide accounting to more than 25% of new cases diagnosed in 2012
• Breast, colorectal, and lung account for more than 43% in women, excluding non-melanoma skin cancer
• Cervical cancer accounts for 8% of all cancers in women, excluding non-melanoma skin cancers
• Lung cancer is most common cancer in men worldwide contributing nearly 17% of the total number of new cases diagnosed in 2012
• Lung, prostate, and colorectal cancers make up almost 42% of all cancers in men, not counting non-melanoma skin cancer
• Stomach and liver are also common contributing to more than 5% of cancers

Carcinogenesis

• Environmental factors, chemicals, radiation, and viruses can all impact carcinogenesis
• Mutations change the genome of somatic cells and inherited mutations
• Gene alterations affect apoptosis and DNA repair
• Activation of growth promoting oncogenes and inactivation of cancer suppressor genes affect carcinogenesis
• These factors lead to expression of altered gene products and loss of regulatory gene products
• This process can then lead to clonal expansion and additional mutation (progression) which causes Heterogeneity
• All of these factors can lead to a Malignant Neoplasm

Environmental Factors

• Chemical Carcinogens
  • Lung cancer caused by Aromatic hydrocarbons
  • Mesothelioma caused by Asbestos
  • Hepatocellular cancer caused by Aflatoxin-B1
  • Gastric cancer caused by Nitrosamines and amides
  • Bladder cancer caused by Azo dyes (Beta-napthylamine)
  • Aplastic anemia etc caused by Alkylating agents (Cyclophosphamide)
• Ionizing radiation can promote cancer by damaging cellular genes resulting in gene mutations and the more radiation the body gets the higher the risk mutation and cancer
  • Sources include natural radiation from the earth and space -Nuclear power and weapons industries -Medical tests (e.g., radiographs)
• Radiotherapy, while helpful, also raises cancer risk
• UV radiation has sun exposure in childhood
• Skin type I or II (freckles) are also predisposing factors
• Arsenic, ionizing radiation, burn/vaccination scars, and immunosuppression are also triggers

Chromosomal Abnormalities

• Balanced translocations include
  • Philadelphia chromosome t(9;22) CML 90% (fusion gene BCR/ABL with tyrosine kinase activity)
  • t(8;14) involving c-myc Burkitt's lymphoma
• Point mutations
  • H-ras (Chemical induced cancers)
• Deletions of tumor suppressor genes
  • Deletion of Rb gene located on chromosome 13q 14 (Retinoblastoma)
• Gene amplification
  • Neuroblastoma

Viruses

• DNA viruses include
  • Human papilloma viruses (HPV)
    • 16 and 18 (squamous cell cancers of cervix and mouth) 'High risk'
    • 6 and 11 (Genital warts)
  • Epstein Barr virus (EBV) for Burkitt's lymphoma, Nasopharyngeal cancer and B-cell lymphomas
  • Hepatitis B (HBV) for Hepato-cellular cancer
  • RNA viruses include Human T-cell Leukemia Virus type -1 (Leukemia and lymphoma)
  • Hepatitis C virus (HCV) RNA flavivirus
  • (Hepatitis D Incomplete RNA virus)

Clinical Features of cancer

• Finger clubbing is a clinical feature caused by Carcinoma of the bronchus
• Lung cancer symptoms include cough (80%), Haemoptysis (70%), Dyspnoea (60%), and chest pain.
• It can also manifest as pneumonias-recurrent or slowly resolving and Loss of appetite & weight loss
• Lung cancer signs include Cachexia, Clubbing, Anaemia, HPOA, Lymphadenopathy, Metastases and Complications
• Horner's syndrome can be seen as a clinical feature
• It show features Enophthalmos, Meiosis – unopposed parasympathetic activity causing pupillary constriction and Ipsilateral facial anhydrosis – damage to superior cervical ganglion exists
• Partial ptosis – paralysis of LPS (levator palpebrae superioris) can also be seen

Colon Cancer

• Left side causes include Bleeding/mucus, altered bowel habit, obstruction, Tenesmus and Mass
• Right side issues include Reduced weight, Anaemia, Abdominal pain and Obstruction
• Both sides commonly cause Abdominal mass, Perforation, Haemorrhage and Fistula

Hodgkin's Lymphoma

• You may see Enlarged painless, nontender, rubbery superficial lymphadenopathy
• 65% of cases result in cervical lymphadenopathy (axillary and inguinal)
• 25% yield constitutional upset (fever, weight loss, night sweats, pruritus)
• Pel-Ebstein fever is a fever for 3-10 days followed by no fever for 3-10 days and is Classically associated with Hodgkins Lymphoma

Diagnostic Features of Melanoma

• Any of following changes in a naevus or pigmented lesion can suggest diagnosis:
• Size : recent increase
• Shape: irregular outline
• Colour: variation
• Erythema: at edge
• Crusting, oozing or bleeding
• Itch: common
• Melanoma skin cancer risk in the UK
• 1 in 41 UK females
• 1 in 35 UK males
• 86% of melanoma skin cancer cases in the UK are preventable

Cancer Screening Methods

• Breast: Self-examination/mammography and BRCA1 and BRAC2 mutation in Jewish women
• Cervix: Cervical cytology/human papilloma virus testing
• Colon/rectum: faecal occult blood/flexible sigmoidoscopy
• Lung: Spiral computed tomography (CT) or chest radiography
• Neuroblastoma: Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA)
• Oral: Examination of the mouth
• Ovary: CA125 and/or ultrasonography
• Prostate: Prostate-specific antigen (PSA)
• Skin (melanoma): Examination for moles
• Stomach: Helicobacter pylori testing; breath test/endoscopy
• Testis: Self-examination Investigations include, chest radiograph, positron emission tomography, genetic analysis and cytology

Biopsy

• Excisional Biopsy: Complete lesion removed with margin of normal skin down to adipose tissue. Useful if suspect melanoma, skin cancer, small bulla
• Cross-section wedge of tissue through center of lesion. Useful when lesion is too big to excise and diagnosis is unsure (e.g., keratoacanthoma vs. squamous cell carcinoma)
• Horizontal shave of the skin lesion with only superficial portion of dermis. Use only to remove benign lesions, as may not get entire depth of lesion. Leaves largest scar. Never use if suspect melanoma
• For sampling possible cancers, tumors, and inflammatory skin conditions. Multiple biopsies can be done to obtain more extensive sampling

Tumour Markers

• Risk of false negative/positive LIMITS use of tumour markers to monitoring treatment responses/detecting recurrences in patients already diagnosed with cancer
  • Tumour marker Carcinoembryonic antigen (CEA) means there is high levels in Colon, pancreas, stomach and breast cancers
  • Alpha-fetoprotein (AFP) presents with high levels in liver and testicular germ cell cancers
  • CA125 registers high levels in ovarian cancer
  • Prostate Specific Antigen (PSA) exhibits high levels in prostate cancer

Oral Cancers

• Oral squamous cell carcinoma is the 10th most common cancer worldwide
• It accounts for 3% of total cancers
• Oral squamous cell cancer was historically older males (incidence is increasing in younger adults and females)

Risk Factors.

• Old age, male gender, tobacco, smoked and/or chewed, alcohol,Betel (areca) use, as in paan chewing, Sun exposure (lip) and Lichen planus
• lonising radiation, immunosuppression and graft-versus-host disease, Low socioeconomic status and infections with human papillomavirus, Candida or syphilis are all risk factors

Effects of BQ Chewing on Mouth

• Occlusal tooth surface wear
• Betel chewer's mucosa (BCM)- brownish red discolouration of mucosa, tenacious quid paricles, tendency to desquamation and peeling. Histologically epithelial hyperplasia and amorphous deposits calcium granules and HPV 11, 16, 18
• Resolves on complete cessation of habit
• Oral precancerous lesions and malignancy - erythroleukoplakia, oral submucous fibrosis (OSMF), OSCC

Other Malignant Oral Neoplasms

• Epithelial malignancies includes Melanoma, Maxillary antral carcinoma, Glandular carcinoma and Intra-bony carcinoma
• Sarcomas Osteosarcoma, Rhabdomyosarcoma and Kaposi sarcoma and Secondary carcinomas are also types of oral neoplasms
• Can show Within lymph nodes (e.g. metastasis from the mouth, within bone (e.g. Metastasis from lung, breast, kidney etc) or Lymphoreticular neoplasms
• Lymphomas also another classification

Clinical Features of Oral Squamous Cell Carcinoma

• Granular ulcer with fissuring or raised exophytic margins
• Red lesion also known as Erythroplakia, White lesion or Leukoplakia,Mixed white and red lesion - speckled and Indurated ulcer - Lesion fixed to underlying tissue or to overlying skin or mucosa
• Another factor may be Lump or Non-healing extraction socket, Lymph node enlargement, Pain or numbness and Loose tooth
• Possible other factors include Dysphagia and Weight loss

Location

• It is Common to find OSCC sites include lips, lateral border of tongue and floor of the mouth
• In paan or betel quid chewers may involve buccal mucosa or commissure region
• Reverse smokers may develop carcinoma of palate

Diagnosis

• History is very important and and detailed examination is required
• Lesions with a high index of suspicion e.g. nonhealing ulcer persisting > 3 weeks
• Potentially malignant (precancerous lesions) can point to carcinoma
• Investigations:
• Lesional biopsy
• Fine needle aspiration of regional lymph nodes and Imaging via Jaw radiographs (Orthopantomograph)
• Chest radiographs, magnetic resonance/ computed tomography of head & neck
• Bronchoscopy – to exclude chest lesions and Endoscopy are all useful

TNM Classification

• Tx means No available information
• TO means No evidence of primary tumour
• Tis means Only carcinoma in situ
• T1, T2, T3, T4- Increasing size of tumour
• Nx: Nodes could not or were not assessed
• NO: No clinically positive nodes
• N1: Single ipsilateral node less than 3cm in diameter
• N2a: Single ipsilateral node 3-6cm N2b: Multiple ipsilateral nodes less than 6cm
• N2c: Bilateral or contralateral nodes less than 6cm
• N3: Any node greater than 6cm Distant metastasis was not assessed
• Mx: Distant metastasis was not assessed
• MO:MO: No evidence of distant metastasis
• M1: Distant metastasis is present
• T1, maximum diameter 2cm; T2, maximum diameter 4cm; T3, maximum diameter over 4cm; T4, tumour greater than 4cm in diameter, with involvement of adjacent anatomical structures.

Management

• Locally involves Curative surgery +/- neck dissection and Radiotherapy
• Regional Spread includes Debulking surgery and Radiotherapy
• Distant Metastases (PALLIATION) causes the need for Palliative surgery, Radiotherapy and Chemotherapy

Managing Radiotherapy

• Dental Management of patients receiving Radiotherapy to the Head and Neck must be handled with care
• Before treatment, you must maintain Meticulous Oral Hygiene, institute preventive dental care and extract unsalvageable teeth
• During, implement Normal saline mouth washes, Benzydamine, Nystatin and Salivary substitute
• Patient is encouraged to practice Jaw-opening exercises
• After, Maintain oral hygiene, Continue preventive dental care and treat Xerostomia

Oral Complications

• Week 1 yields Nausea with Week 2+: Mucositis
• infections occur later and Dry mouth comes following week 3+ signs
• Also Vomiting and Taste changes arise along with caries and tooth hypersensitivity
• Additionally Pulp pain and necrosis, Trismus, Osteoradionecrosis and craniofacial defects may arise

Prognosis

• Stage | yields T1 NO MO at 85%
• Stage || shows T2 NO MO with rate of 65% rate
• Stage III shows T3 NO MO, or T1, T2 or T3 N1 M0 while survival 40%
• Stage IV: Any T4, N2, N3 or M1 shows 10% survival rate
• A multidisciplinary approach involving a Dentist, Oral and Maxillofacial surgeon / ENT / Plastic surgeon, Oral Medicine / Pathology, Oncologist, Radiotherapist, Speech And Language Therapist, and Macmillan Nurse and Palliative Care Team improves patient outcome