Table of Contents

I. Introduction
• Definition of Oral Cancer
• Prevalence of Oral Cancer
II. Risk Factors for Oral Cancer
• Tobacco Use and Alcohol Consumption
• HPV-16 Virus
III. Symptoms of Oral Cancer
IV. Diagnosis and Treatment of Oral Cancer
• Multidisciplinary Approach to Treatment
• Side Effects of Treatment
V. Current Research on Oral Cancer
• DNA Changes and Gene Therapy
• Epidermal Growth Factor
• New Chemotherapy Drugs and Vaccines

In reality, oral cancer is cancer of many organs. It includes lips, tongue, cheeks, the floor of the mouth, hard and soft palate, sinuses, and pharynx (throat). It can be life-threatening if not diagnosed and treated early. As it prospers without producing pain or symptoms it remains unnoticed by the patient in the early stages. It is the eighth most common cancer worldwide. The burden of oral cancer is particularly high in South Central Asia due to risk factor exposures. According to WHO, there are an estimated 657,000 new cases of cancers of the oral cavity and pharynx each year, and more than 330,000 deaths. The prevalence of oral cancer is particularly high among men.

Oral cancer can occur through the use of tobacco and alcohol. The evidence that smokeless tobacco causes oral cancer was confirmed recently by the International Agency for Research on Cancer 1.  It can also occur through the exposure to the HPV-16 virus (human papilloma virus version 16). About 90% of cancers in the oral cavity are attributed to tobacco use and excessive alcohol consumption. The oral cancer risk increases when tobacco is used in combination with alcohol or areca nut 2. For a small percentage of people (under about 10%) cause of oral cancer is still unidentified. Oral cancers have an 80 to 90 % survival rate if diagnosed at early stages of development. However, the majority are diagnosed at later stage accounting for the 43% of the death rate. A high treatment-related morbidity has also been seen in survivors. Unfortunately, in case of oral cancer, late stage diagnosis is occurring due to a lack of public awareness. Also, there is a lack of a national program for opportunistic screenings 3. Historically the death rate associated with this cancer is particularly high not because it is hard to discover or diagnose, but due to the cancer being routinely discovered late in its development.  The advent of a virus, HPV16 is contributing more to the incidence rate of oral cancers, particularly in the posterior part of the mouth (the oropharynx, the tonsils, the base of tongue areas). They don’t produce visible lesions or discolorations that have been the early warning signs of the disease process.

Other than common cancer symptoms like weight loss etc., oral cancer is characterized by –

  • Swellings/thickenings, lumps or bumps, rough spots/crusts/or eroded areas on the lips, gums, or other areas inside the mouth
  • The development of velvety white, red, or speckled (white and red) patches in the mouth (Figure 1)
  • Unexplained bleeding in the mouth
  • Unexplained numbness, pain/tenderness in any area of the face, mouth, or neck
  • Persistent sores on the face, neck, or mouth that bleed easily and do not heal within 2 weeks
  • A soreness or feeling that something is caught in the back of the throat
  • Difficulty chewing or swallowing, speaking, or moving the jaw or tongue
  • Hoarseness, chronic sore throat, or change in voice
  • Ear pain
  • A change in the way teeth or dentures fit together
  • Dramatic weight loss

Treatment begins only after a definitive diagnosis of cancer stage. Cancer treatment is a multidisciplinary approach involving surgery, radiation therapy, chemotherapy, dentistry, and rehabilitation. The actual curative treatment modalities are chemotherapy with concurrent radiation, sometimes combined with surgery. Chemotherapy while able to kill cancer cells itself but is currently not used as a monotherapy for oral cancers. A powerful component of treatment strategy is to sensitize the malignant cells to radiation in order to reduce the size of any malignancy prior to surgery. For the later stage oral cancer, surgery may require reconstruction of portions of the oral cavity or facial features. An important side effect of head and neck radiation therapy is xerostomia (dry mouth). Recent research suggests that a drug amifostine can help reduce this side effect by limiting radiation damage to salivary glands.

Important research into oral and oropharyngeal cancer is underway. Study of DNA changes occurring in oral cancer has shown mutation of the p53 gene. p53 protein helps to destroy cells and damage to p53 DNA can lead to increased growth of abnormal cells. Tests of p53 gene alterations, project to allow early detection and better define surgical margins (check to see if all cancer cells have been removed). In another approach abnormal tumor suppressor genes (such as the p53 gene) of oral cancer cells are replaced with a normal copy, this technique is called Gene therapy. In this, it is being studied to check whether is it possible to restore normal growth control. In some oral cancers papillomavirus (HPV) DNA becomes mixed together with the patient’s own DNA. Some parts of the HPV DNA instruct the cells to inactivate the p53 protein. Studies are underway to determine whether tests to detect HPV DNA may help in diagnosing these cancers.

One of the growth factors linked to oral and oropharyngeal cancers is called epidermal growth factor (EGF). Oral and oropharyngeal cancers with too many EGF receptors tend to be especially aggressive. Drugs are being studied to target cells with numerous EGF receptors. Basically, these drugs prevent EGF from promoting cancerous growth and may also help the patient’s immune system recognize and attack cancer. With the preliminary studies a drug, C225, makes radiation therapy more effective in killing head and neck squamous cell cancers. New chemotherapy drugs like – Intraarterial chemotherapy (injection of drugs into arteries feeding cancer) is being tested in combination with radiation therapy in an attempt to improve their effectiveness. In another approach intralesional chemotherapy is being tested using drug solution and preliminary results have been promising. Vaccines are also being studied to treat people with cancer by helping their immune system to recognize and attack the cancer cells. They can be useful for papillomaviruses induced oral cancers.

A comprehensive approach is needed for oral cancer to include health education and literacy, risk factor reduction and early diagnosis. In select regions with high incidence, oral cancer screening in high-risk individuals has been trialed.

References

  1. Reibel J. Tobacco and oral diseases: an update on the evidence, with recommendations. Med Princ Pract 2003;12:22–32.
  2. Cogliano V, Straif K, Baab R, Grosse Y, Secretan B, Ghissassi FEI. Smokeless tobacco and tobacco-related nitrosamines. The Lancet Oncology 2004;5:708
  3. Jitender SSarika GVarada HROmprakash YMohsin K. Screening for oral cancer. J Exp Ther Oncol.2016 Nov;11(4):303-307.