Oral cancer overview

# Overview
Oral cancer (or mouth cancer) is a type of head and neck cancer that involves any cancerous tissue growth located in the oral cavity. Oral cancer is a malignant growth that affects any part of the oral cavity, including the lips, gums, tongue, inside lining of the cheeks, roof of the mouth and floor of the mouth. It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types.

# Classification
Oral cancer can be classified into three types based on the potential to spread to other parts of the body such as malignant tumors,precancerous conditions, and benign tumors. Most common type of malignant tumor of the mouth is squamous cell carcinoma. Squamous cell carcinoma is further classified by macroscopic and microscopic features. About 5% of oral cavity cancers are rare, malignant tumors that start in different types of cells in the oral cavity. These include: salivarygland cancer, melanoma, bone and soft tissue sarcomas, lymphomas and extramedullary plasmacytomas, hodgkin lymphoma, and non-Hodgkin lymphoma metastatic cancer.

# Pathophysiology
It is understood that oral cancer occurs as a the result of carcinogen-metabolizing enzymes, alcohol, tobacco and genetic factors. Cytotoxic enzymes, such as alcohol dehydrogenase, result in the production of free radicals and DNA hydroxylated bases. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is cytotoxic in nature. Cigarette smoke has various carcinogens that can lead to oral cancers. Low-reactive, free radicals in cigarette smoke interact with redox-active metals in saliva. The development of oral cancer is the result of multiple genetic mutations. These mutations occur in tumor suppressor genes (TSGs) and oncogenes. Squamous cell carcinoma is the most common malignancy of the oral cavity. It typically has three gross morphological growth patterns: exophytic, ulcerative, and infiltrative. Microscopically, oral cancers are broadly based and invasive through papillary fronds. Oral cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses.The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen

# Causes
Common causes of oral cancers include pre-malignant lesion, tobacco, alcohol, human papillomavirus, and hematopoietic stem cell transplantation. Seventy-five percent of oral cancer cases occur due to tobacco. It causes irritation of the mucous membrane in the mouth. HPV type 16 is the most common sub-type of human papilloma virus associated with oral cancer.

# Differentiating Oral cancer from other diseases
Oral cancer must be differentiated from actinic keratosis, dermatologic manifestations of oral leukoplakia, erythroplasia, lichen planus, and mucosal candidiasis.

# Epidemiology and Demographics
The prevalence of oral cancer is estimated to be 91, 200 cases annually. The incidence of oral cancer is approximately 10.5 adults per 100,000 individuals worldwide, with a mortality rate of 1.2 per 100,000 individuals each year. Males are more commonly affected by squamous cell cancer of the oral cavity than females. The male to female ratio is approximately 6 to 1. Females are more commonly affected with adenocarcinoma of the hard palate. Oral cavity cancer more commonly affects individuals of the black population. Oral cavity cancer typically affects individuals of the lower-income patients.

# Risk factors
The most potent risk factor in the development of oral cancer is alcohol intake and tobacco use. The other risk factors include male gender, age over 55 years, ultraviolet light, Fanconi anemia, dyskeratosis congenita, HPV infection, graft-versus-host disease (GVHD), mouthwash and irritation from dentures.

# Screening
There is insufficient evidence to recommend routine screening for oral cancer.

# Natural History, Complications and Prognosis
If left untreated, patients with oral cancer may progress to develop non-healing ulcer, which demonstrates growth over time. A neck mass may develop, possibly causing a mass defect. Depending on the extent of the tumor at the time of diagnosis, the prognosis varies.  The 5-year survival rate for oral cancer diagnosed early is 75% compared to 20% for oral cancer diagnosed late. Complications of oral cancer include difficulty speaking, dysphagia , weight loss, bleeding and even death.

# Staging
According to the TNM staging system by the American Joint Committee on cancer, there are four stages of oral cancer based on the tumor size, lymph nodes involved, and metastasis.

# History and Symptoms
A positive history of tobacco chewing or smoking, excessive alcohol intake, poor oral hygiene, metallic denture, betel quid use, diet rich in meats and HPV infection in sexual partner is suggestive of oral cancer. The most common symptoms of oral cancer include a sore, irritated lump or thick patch in the mouth, lip, or throat; a white or red patch in the mouth; persistent mouth pain; a lump in the neck; loose tooth; bleeding in the mouth; pain in one ear without hearing loss; weight loss, etc.

# Physical Examination
Common physical examination findings of oral cancer include a lump or thickening in the oral soft tissues, soreness, difficulty chewing or swallowing, ear pain, difficulty moving the jaw or tongue, hoarseness, numbness of the tongue or swelling of the jaw that causes dentures to fit poorly.

# Laboratory Findings
Some patients with oral cancer may have elevated liver function tests, abnormal urea and electrolyte measurements, elevated calcium levels. Serum ferritin, alpha-anti-trypsin, and alpha-anti-glycoprotein levels may be increased in high-stage cancer of oral cavity; while those at any stage of the disease will have increased haptoglobin levels. Prealbumin levels are decreased slightly in persons at any stage.

# X-ray
There are no x-ray findings associated with oral cancer. However, a chest x-ray may be helpful to diagnose metastases in the lungs, a site for second primary carcinoma and metastasis in hilar lymph nodes, ribs, or vertebrae. Jaw radiography may show invasion but may be inadequate to exclude bone invasion.

# CT
Neck CT scans may be helpful in the diagnosis of oral cancer. CT scans can provide information about the size, shape and position of any tumor and may help identify enlarged lymph nodes.

# MRI
Neck MRI's may be helpful in the diagnosis of oral cancer. MRI's can provide detailed view of cancer spread. Magnetic resonance imaging offers an advantage over computed tomographic scans in the detection and localization of head and neck tumors and in the distinction of lymph nodes from blood vessels.

# Other Imaging Findings
A PET scan may be diagnostic of spread of oral cancer. FDG-PET (18-fluorodeoxyglucose positron emission tomography) scanning is useful to identify the extent of cervical node metastasis.

# Other Diagnostic Studies
Biopsy of the tumor tissue is diagnostic of oral cancer. Other diagnostic studies for oral cancer include endoscopy, indirect pharyngoscopy, laryngoscopy, exfoliative cytology, barium swallow, chest x-ray and bone scan.

# Medical Therapy
The predominant therapy for oral cancer is surgical resection, radiation therapy, or a combination of both. Adjunctive chemotherapy, radiation, chemotherapy may be required. Radiation in the form of external-beam radiation therapy (EBRT) or interstitial implantation is used. Advantages of radiotherapy are that normal anatomy or function are maintained, and general anesthesia is not needed. Disadvantages of radiotherapy are that it is inefficient to treat large tumors, subsequent surgery is more difficult, oral mucositis, dry mouth (xerostomia), osteoradionecrosis (ORN) etc.

# Surgery
Surgery is the mainstay of treatment for oral cancer. Surgical resection of full-extent of the oral cavity lesion should be done. Only surgical resection is done when oral cancer has been detected early but not yet metastasized. In advanced-stages and recurrent cancers, surgery is done in combination with radiation therapy, chemotherapy or targeted therapy. Depending on the stage of oral cancer, one or more of the various procedures listed are recommended: Tumor resection, mohs micrographic surgery, full or partial mandible resection, glossectomy, maxillectomy, Laryngectomy, Neck dissection, partial or selective neck dissection, modified radical neck dissection or radical neck dissection.

# Primary Prevention
Effective measures for the primary prevention of oral cancer include tobacco cessation, alcohol cessation, HPV vaccine, and avoiding excessive sun exposure.