Oral Cancer PDF

Oral cancer Dr. Qaisar  Squamous cell carcinoma (SCC) is the predominant form of oral cancer and accounts for greater than 90% of malignant pathology. Other forms include salivary gland tumors, mesenchymal tumors, lymphoma, and melanoma It’s a disease of older age. More tha...

Oral cancer Dr. Qaisar  Squamous cell carcinoma (SCC) is the predominant form of oral cancer and accounts for greater than 90% of malignant pathology. Other forms include salivary gland tumors, mesenchymal tumors, lymphoma, and melanoma It’s a disease of older age. More than 92% of oral and pharyngeal cancers occur in individuals older than 40 years, with the average age being 63  Oral carcinogenesis appears to evolve through a complex, multistage process involving biomolecular changes that precede premalignant lesions, which in turn precede invasive cancer. The genetic changes caused by exposure to carcinogens like tobacco and alcohol tend to accumulate over time in the entire mucosa exposed to this insult. Nature of SCC Oral carcinogenesis appears to evolve through a complex, multistage process The fundamental mechanism in carcinogenesis is thought to be the cellular balance between oncogenes and tumor suppressor genes. The proto-oncogenes stimulate cell growth and proliferation and are under negative control of the tumor suppressor genes, which prevent overgrowth  So, cancer may therefore arise either from activation of a proto-oncogene or due to loss of a tumor suppressor gene. Numerous genetic events are required to cause a cancer, but the most frequently observed molecular abnormality is mutation of the 'p53 tumor suppressor gene‘ which is seen in 40-70% of malignant lesions and 20% of premalignant lesions. Etiology The cause of oral SCC is multifactorial. No single causative agent or factor (carcinogen) has been clearly defined or accepted, but both extrinsic and intrinsic factors may be at work  1. Tobacco smoking & Smokeless tobacco use: studies revealed that the proportion of smokers among patients with oral carcinoma is 2-3 times greater than the general population. Also pipe and cigar smoking carries a greater oral cancer risk than does cigarette smoking. The risk of oral SCC is dose and time dependent. Chronic Smokeless tobacco use increases the risk of oral SCC 2-26 times. Approximately 50% of all oral cancers in smokeless tobacco users occur at the site where the tobacco is habitually placed.  2. Betel quid: is a compound of natural substances chewed for their psychostimulating effects. Among betel quid users in Asia, the lifetime risk of developing oral cancer is a remarkable 8%. 3. Alcohol: It is uncertain whether excessive alcohol consumption alone can initiate carcinogenesis, although it is well established that alcohol in combination with tobacco is a significant risk factor for oral cancer development (the risk increases 15 times).  4. Iron deficiency: especially severe chronic form known as Plummer-Vinson syndrome. People who are deficient in iron tend to have impaired cell-mediated immunity, and iron is essential to the normal functioning of epithelial cells of the upper digestive tract. 5. Vitamin A deficiency: producing excessive keratinization of the skin and mucous membrane.  6. Radiation: this includes ultraviolet radiation and X-irradiation, which reduces immune reactivity and produces chromosomal abnormalities. 7. Phenolic agents: there is increased risk of oral cancer for workers in the wood products industry chronically exposed to certain chemicals, such as phenoxyacetic acids.  8. Syphilis (tertiary stage): has long been accepted as having a strong association with the development of dorsal tongue carcinoma. Also the arsenical agents and heavy metals that were used to treat syphilis before the advent of modern antibiotic therapy have carcinogenic properties but today syphilis associated oral malignancies are rare because the infection is typically diagnosed and treated before the onset of the tertiary stage.  9. Candidal infection: hyperplastic candidiasis also called candidal leukoplakia is considered a precancerous condition. 10. Oncogenic viruses: human papilloma virus is implicated in oral cancer development especially subtypes 16, 18, 31 and 33. 11. Immunosuppression 12. Oncogenes and Tumor suppressor genes: which are chromosomal components capable of being acted on by a variety of causative agents. Site distribution The importance of the "cancer-prone crescent" and its significance is related to the postulate that most oral cancers should occur in mucosa where saliva pools due to gravity exposing it to salivary carcinogens. The site distribution of oral SCC is varied but the general trend is as follows:-  Tongue 35% (31% lateral border, 2% tip and 2% dorsum). Floor of mouth 30% (25% anterior and 5% posterior) Lower alveolus 15%. Buccal mucosa 10%. Upper alveolus 5%. Hard palate 3% Retromolar trigon 2% Clinical presentation Despite the fact that the oral cavity is an easily accessible site for the patient and the clinician, a surprisingly large number of oral tumors present late because of the painless and rather vague nature of the symptoms Clinical manifestation includes Exophytic or mass forming lesion which typically has a surface that is irregular, fungating, papillary, or verruciform, and its color may vary from normal to red to white, depending on the amount of keratin and vascularity. The surface is often ulcerated, and the tumor is indurated on palpation  Endophytic growth pattern which has a depressed, irregularly shaped, ulcerated, central area with a surrounding rolled border of normal, red or white mucosa. The rolled border results from invasion of the tumor downward and laterally under adjacent epith. with induration of the underlying tissues.  Leukoplakic, Erythroplakic or combined Erythro- leukoplakic lesions (speckled leukoplakia) which has a high incidence of malignant transformation  A thorough examination of the upper aerodigestive tract mucosa should be performed in every case since synchronous multiple primary cancers occur in approximately in 4% of patients with oral cancers. Symptoms Lesions in the floor of mouth or tongue may be painful, infiltrative lesions of the floor of mouth also may extend to invade bone anteriorly, muscles of the floor of mouth deeply, or tongue posteriorly. Patients may complain of difficulty in swallowing or speaking, which becomes even more pronounced when the tumor spreads to the floor of the mouth  Early spread to the alveolus and periosteum of the mandible is common; clinical fixation of the tumor to the mandible indicates periosteal involvement, and direct bone invasion may be present in a high number of cases. Patients may report pain while chewing intermittent bleeding, loose teeth or ill-fitting dentures in gingival or alveolar ridge lesions Some symptoms like trismus or altered sensation or anesthesia of lower lip may signify locally advanced disease Clinical staging TNM system An aid to planning treatment Aid in prognosis Comparison of results of treatment Facilitate exchange of information between treatment centers  As a general rule, more advanced stage implies a worse prognosis. Initial staging is performed by using all available clinical and radiographic data (cTNM). Final staging incorporates histopathologic data if surgery is performed (pTNM).  TNM staging depends purely on the anatomic extent of disease and does not account for the many biologic, molecular, or host characteristics that are known to influence prognosis. What is the third dimention of the primary tumor (depth)? What is the relation with L.N. metastasis? Distant metastasis M MX: Distant metastasis can not be assessed M0: No distant metastasis M1: Distant metastasis In 2017 the 8th Edition of the TNM system introduced major changes: For the T category of oral SCC the depth of invasion (DOI) is acknowledged. Pathologically, DOI is measured from the level of the basement membrane of the closest adjacent normal mucosa to the deepest point of tumor invasion. The other change from prior editions of the TNM system is the elimination of the DOI category.  For the N category extranodal extension (ENE) has been added as a prognostic variable for regional lymph node metastases in addition to the size of metastatic lymph nodes. Regional L.N. Physical examination Tumor's location, size, and relationship structures Fixation to the mandible. Proximity to the midline often guides the decision for unilateral versus bilateral neck dissection. Trismus or decreased tongue mobility may be an indication of invasion into deeper structures.  Cranial nerve deficits suggest tumor involvement, which may increase suspicion for perineural spread The status of the dentition should be assessed in patients in whom radiation therapy may be indicated because of the risk for xerostomia- related caries and osteoradionecrosis. Plans should be made for non-viable teeth to be removed at the time of surgery or before radiation therapy.  Biopsy of the primary tumor is required for histologic diagnosis and treatment planning Lymph nodes in the neck must be palpated carefully to assess for cervical metastasis or other abnormalities. Palpable nodes should be evaluated for size, location, and fixation to skin or deeper structures  Pretreatment imaging is important to evaluate: 1- The tumor size and extent. 2- Involvement of adjacent anatomic structures 3- Staging the cervical lymph nodes. 4- Tumor invasion for the bone especially the mandible.  Conventional radiographs CT scan: excellent bone details and adequate soft tissue enhancement MRI: superior soft tissue details and lack of ionizing radiation Ultrasound PET scan PET has shown promise in the evaluation of metastatic disease, tumor recurrence, and treatment response after chemotherapy or radiation therapy. Treatment goal Cure of the cancer Preservation or restoration of speech, mastication, swallowing, and external appearance Minimization of the sequelae of treatment such as dental decay, osteonecrosis of the mandible, and trismus. Awareness of the risk of subsequent primary tumors and their management.  The main modalities of treatment are surgery, radiotherapy and chemotherapy (others: immunotherapy, photodynamic therapy, and laser) In general, small and superficial tumors of the oral cavity are equally amenable to being cured by surgical resection or radiotherapy.  So the use of a single modality is preferred as the definitive treatment in early stage (T1 and T2) tumors of the oral cavity. When the end point of treatment, that is, cure of cancer, is comparable, other factors must play a role in the selection of initial treatment. These factors include complications, cost, convenience, compliance, and long-term sequelae of treatment. Considering these factors, surgery is the preferred treatment for T1 and T2 tumors of the oral cavity  In advanced stage (T3 and T4) oral cancer combining surgery with adjuvant postoperative radiotherapy offers improved locoregional control but does not improve survival. The most important high-risk features for combining surgery and radiotherapy are 1- positive margins 2- extranodal spread 3- multiple +ve nodes 4- perineural and vascular invasion 5- L.N. level IV and V Surgical treatment Surgical excision is one of the two mainstays of loco-regional treatment of oral cancer. It allows histopathological assessment of the clearance margins of the tumor together with further information regarding tumor spread and dynamics. Factors that influence the choice of surgical treatment for a primary tumor of the oral cavity are: Tumor factors 1- Size, site, 2- Proximity to bone. 3- Previous treatment. 4- Depth of invasion. 5- The histological characteristics of the primary tumor (i.e., type and grade). 6- Status of cervical lymph nodes.  Patient Factors. 1- Age 2- Occupation 3- Socio-economic considerations 4- General medical condition. 5- Lifestyle (smoking and drinking) 6- Previous treatment.  Physician Factors 1- Surgery. 2- Radiotherapy. 3- Chemotherapy. 4- Nursing & rehabilitation services. 5- Dental. 6- Prosthetics. 7- Support services. Rules to follow The excision of the lesions should include at least 1 cm of adjacent normal tissues as safe margin. Superficial lesions of the floor of mouth, buccal mucosa and soft palate can be excised through peroral approach also T1 and most T2 lesions of the anterior two thirds of the tongue (oral tongue) where the mobility of the tongue is not restricted, and the tumor does not extend to involve the adjacent floor of the mouth or cross the midline are amenable for partial glossectomy through per oral approach Surgical access Peroral (transoral) Mandibulotomy Lower cheek approach Visor approach Upper cheek approach Peroral (transoral) For small, anteriorly located tumors. Lower cheek flap It requires a midline lip-splitting incision that is continued laterally into the neck for exposure and neck dissection. This approach provides excellent exposure for tumors of the oral cavity that are posteriorly situated and not accessible for peroral approach except those of the upper gum and hard palate. Upper cheek flap The upper cheek flap approach (the Weber-Ferguson incision and its modifications). is raised using a median upper lip split and carrying the incision around the nose with the corresponding mucosal incision in the upper gingivobuccal sulcus. It is required for resection of larger tumors of the hard palate and upper alveolus, particularly if they are posteriorly located. Visor Flap It provides sufficient exposure for anteriorly located lesions but is not satisfactory for tumors located in the posterior oral cavity.  The benefit of this approach is that it avoids a lower lip-splitting incision it produces permanent numbness of the chin because the mental nerves need to be transected for adequate mobilization of the flap. It also may cause sagging of the lower lip and drooling because of a loss of support and sensation. Thus its usefulness is limited. Midfacial degloving flap Through bilateral gingivobuccal incisions is preferable in appropriate cases as this avoids midfacial scar. Mandibulotomy Adequate surgical exposure of tumors located in the posterior oral cavity may be obtained using a lip-splitting mandibulotomy Management of the Neck The status of the cervical lymph nodes is the most important prognostic factor in SCC of the head and neck. The overall survival rate decreases by approximately 50% in patients with metastases to the cervical lymph nodes.  Approximately 40% of patients will initially be found to have evidence of regional nodal metastasis. Therefore, management of the cervical lymphatic is an important component of the overall treatment of patients with head and neck cancer. The head and neck drain into an extensive network of cervical lymphatic, in a predictable manner for each site. Knowledge of the anatomy of the regional lymphatic system is therefore important. Anatomy and biology of lymphatic metastasis Cervical lymph nodes are categorized into five nodal levels, and additionally levels VI and VII encompassing central compartment and superior mediastinal nodes. Levels I, II, and V are further subdivided into sublevels A and B. For primary tumors in the oral cavity, the regional lymph nodes at highest risk for early dissemination by metastatic cancer are limited to levels I, II, and III. Clinical evaluation and diagnostic imaging Ultrasonography, CT, and MRI scans, and PET scans. Although the presence of metastatic involvement of a lymph node is a histologic, not a radiologic diagnosis, there are characteristic changes apparent on CT and MRI suggestive of metastatic SCC includes 1- Enhancement 2- Poorly circumscribed margins 3- Central necrosis 4- L.N. size > 1cm. In diameter Note:- The size does not always correlate with the presence of tumor involvement, a small lymph node less than 1 cm in diameter may still harbor foci of tumor cells. lymph node size greater than 1 cm in diameter does not automatically herald metastatic cancer, because reactive lymphadenopathy following infection, inflammation, or surgical intervention may result in lymph nodes of such size Classification of Neck Dissection Radical Neck Dissection (RND) Modified Radical Neck Dissection (MRND) Selective Neck Dissection (SND) Extended Neck Dissection Radical Neck Dissection (RND) involves the en bloc removal of 1- Ipsilateral L.N. from levels I through V 2- Spinal accessary nerve (SAN) 3- Internal jugular vein (IJV) 4- Sternocleidomastoid muscle (SCM) Modified Radical Neck Dissection (MRND) one or more non lymphatic structures are preserved during the dissection MRND can be subclassified as follows: 1. Type I MRND preserves the SAN 2. Type II MRND preserves the SAN and IJV 3. Type III MRND preserves the SAN, IJV, and SCM. This modification is also termed functional neck dissection. Selective Neck Dissection (SND) when one or more lymph node groups are preserved during cervical lymphadenectomy that are routinely removed with RND. The lymph node groups that are removed are dependent on the predictable patterns of metastases from the primary site. The levels of lymph nodes removed are identified (e.g., SND levels I to III) Extended Neck Dissection when one or more lymph node groups or non lymphatic structures, or both, that are not usually involved in RND are removed. lymph node groups include the parapharyngeal, paratracheal, and superior mediastinal nodes. Non-lymphatic structures include the carotid artery, hypoglossal nerve, and paraspinal muscles.  Subclassification into "therapeutic" and "elective" neck dissection refers to the indication for surgery, but does not specify the extent of the dissection Therapeutic neck dissection is used when cervical metastases is detected preoperatively Elective or prophylactic term used when neck dissection is done for potential subclinical cervical metastases  Occult metastases occurs in 20-45% of pt. who were staged clinically as N0. so this is an option to performing neck dissection this may lead to 55-80% of patients undergoing unnecessary neck dissections, along with the associated morbidity, particularly postoperative shoulder dysfunction. Techniques have been used to detect cervical occult metastasis of the clinically negative neck like ultrasound, CT, MRI scans, PET, PET/CT and sentinel lymph node biopsy. Prognostic variables of nodal metastasis Tumor thickness Primary site. Perineural invasion Lymphovascular invasion. Histopathologic grading. T stage  Postoperative follow up Postoperative visit Examination schedule 0-3 months Biweekly examination 3-12 months Monthly examination 1-2 years Examination every 2 months 2-4 years Examination every 4 months 4-5 years Examination every 6 months Radiotherapy It uses ionizing radiation; it is locoregional treatment and should be considered as complementary to surgery rather than competitive. The rationale of radiotherapy: 1- Cells are killed in mitosis. 2- Cancer cells divide more frequently. 3- Malignant cells repair less efficiently. 4- It preserves function  The basic principle is to achieve high dose in the tumor while minimizing the dose to the normal tissues, this is difficult in the head and neck because: 1- SCC is less sensitive to radiation than other types of malignancies requiring higher dose. 2- Better technique precision is required due to the juxtaposition of critically radiosensitive organs like the eyes and the brainstem.  Radiotherapy can be used as a definitive treatment or combined with other modalities, surgery or chemotherapy. It is best at eradicating small volumes of disease but it is more likely to fail if there is a large bulky tumor. Types of radiotherapy 1. External beam radiotherapy (Teletherapy). 2. Brachytherapy Preoperative radiotherapy Preoperative radiotherapy is infrequently used and should not be considered to be a standard of care. Postoperative radiotherapy It should start no later than 6 weeks after surgery. 1- Absolute indications for postoperative irradiation are; involved (positive) margins at the primary tumor resection site and extracapsular spread of involved lymph nodes. 2- Near absolute indications include close (less than 5 mm) margins, two or more involved cervical lymph nodes and invasion of the soft tissues of the neck. 3- The relative indications include; the presence of lymphovascular space invasion and perineural invasion.  Fractionation of radiotherapy Since the maximum radiation in a single dose is limited by the normal tissue tolerance, the total dose is divided into a number of small doses (fractions) 1- Conventional: 65 Gy (Gray) is given in protracted treatment course of 2 Gyx 30 fractions for 42 days (conventional). 2- Hyperfractionation: when the number of fractions is increased beyond the conventional levels, so the ratio of dose/fraction is reduced. The treatment should be given 2-3 times/day with 6 hours interval 3- Acceleration: is reduction in overall treatment time. 4- Continuous hyperfractionated accelerated rad (CHART): 1.5 Gy, 12 days, 3 fractions/ day, 7 days/week. This radiation therapy prevent repopulation of malignant cells. 5- Split courses: designed to reduce the severity of mucosal reaction, so the radiotherapy course is divided into 2 halves separated by 2 weeks, but this may lead to repopulation of tumor cells so it is condemned.  Chemotherapy In SCC of the head and neck chemotherapy is used in combination with radiotherapy and/or surgery in radical treatment or alone in palliative treatment. Failure of cancer treatment is due to inherent or acquired resistance of malignant cells. Classes of chemotherapeutic agents Antimetabolites DNA damaging agents Mitosis inhibitors Cancer cell enzyme inactivators Scheduling of Chemotherapy Before radiotherapy (neoadjuvant or induction) During radiotherapy (synchronous or concomitant) After radiotherapy (adjuvant or subsequent) Chemotherapy can be given as a single agent with reported response rate of 40% or in combination with response rate of 75%. The main outcome measures are: Local control. Survival rate. Concomitant Chemoradiatiorn Use of concomitant chemoradiotherapy is based on a belief that chemotherapy synergistically acts with radiotherapy by: 1- Inhibiting repair of DNA damage caused by radiotherapy, preventing regrowth between radiotherapy treatments 2- In addition it is thought that chemotherapy may treat radio-resistant tumor lineages such as hypoxic cells.  The addition of concomitant chemotherapy to radiotherapy has been shown to be superior to radiotherapy alone for locoregional control and survival in head and neck SCC Palliative treatment and terminal care Treatment is usually radical in intent; also any salvage treatment is aimed to cure the patient. The treatment may progress to palliative and finally to terminal care which is a right to every patient and duty of every health professional. The aim of terminal care is to: 1. Make the patient free of pain. 2. Mobile 3. Sufficiently alert. It is usually home care, in a hospice or in the same hospital.