Background and statistics:
Oral cancer is one of the most challenging malignancies of the head and neck region and remains a major global threat to public health. It accounts for approximately 5% of all cancers globally, while in India it is about 30% of all types of cancer. It is estimated that nearly 60,000 new cases of oral cancer is reported every year in India. It is disheartening to notice that over 5 people in India die every hour everyday because of oral cancer indicating that the disease is highly fatal in nature. Most importantly, it has been noticed that Indians present with oral cancer at a much younger age (i.e. those 40 years or younger) in comparison to the patient from western population. Thus having cancer is in itself tragic, having it at a younger age is cataclysmic. However, if oral cancer is detected at an early stage it not only has a good prognosis, but can increase the survival rate and can improve the quality of life of the patient.
Oral cancer is a multifactorial disease with consumption of tobacco and alcohol remains the major risk factors. Excessive use of tobacco in any available forms (areca-nut, betel-nut, gutkha, bidi, khaini) and heavy alcohol consumption shows combined synergetic effects on oral cancer initiation . Notably, the risk of developing oral cancer is almost five to ten times greater for smokers in comparison to non-smokers. The cancer causing agents present in the tobacco triggers various oncogenetic pathways which plays a vital role in cancer initiation. Interestingly, it has been reported that for patients who quit smoking, the risk for oral cancer declines over time and may approach that of nonsmokers after 10 or more years of cessation. With respect to alcohol consumption, heavy drinkers (4 drinks per day or >4 or7 drinks per week), are always at a high risk of developing oral cancer . Underlying carcinogenic mechanisms are not entirely clear, alcoholic beverages may contain aldehyde itself and various carcinogenic contaminants, such as polycyclic aromatic hydrocarbons and nitrosamines which are known to cancer causing agents. Several studies suggest an association between human papillomavirus (HPV) infection and oropharyngeal cancers, particularly HPV 16 (90-95% of HPV-positive tumors) . The virus releases oncoprotiens which degrades tumor suppressor gene (suppress tumor formation) which may lead to HPV-associated oral cancer. The role of the protective effect of HPV vaccines against oral cancer still remains unclear and need further scientific studies.
A definitive diagnosis requires a biopsy of the oral tissue. Biopsies for histopatholgical diagnosis may be obtained using surgical scalpels or biopsy punches and typically can be performed under local anesthesia. Despite the easy access of the oral cavity to examination, oral tumors are diagnosed in more advanced stages of the disease. Imaging techniques have been recently emerged as non-invasive approaches to detect molecular and cellular changes in living cells and organisms. These techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) could help physicians to screen patients with oral tumors particularly oral carcinoma in early stage of the disease . These advanced imaging studies help in planning the scope of resection and further treatment thereby helping in effective patient management.
Molecular Genetics of oral cancer:
Several research studies have been undertaken to find pathways that are altered in oral carcinoma at molecular level, with a special emphasis on their diagnostic and or prognostic significance. The tumor suppressor gene, p53 is the most commonly altered gene in oral cancer and has been associated with clinical outcome in some studies. In addition, epithelial growth factor receptor (EGFR) expression has been reported in ~40% of the oral cancer cases and is associated with poor clinical outcome. Likewise, there are plenty of other molecular markers such as p63, cyclin D1, VEGF, E-Cad etc which has found to be altered in terms of their expression and are associated with different clinical outcome in oral cancer. Recently, efforts are being made to identify non-invasive saliva based molecular markers for oral cancer diagnosis. In this context, miRNA (small RNA molecular biomarker) in saliva of cancer patients possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of oral cancer. Nevertheless, none of these markers or combinations has been incorporated into large prospective clinical trials. At present, the overall evidence is insufficient to alter clinical practice or to consider aggressive treatment for subsets of patients identified on the basis of the use of molecular markers alone. These markers are not yet available in routine practice.
Treatment planning for oral cancer requires a multidisciplinary approach with surgeons, radiation oncologists, medical oncologists, radiologists, speech/swallowing pathologists and dentists. The clinical stage of the oral cancer determines the treatment strategy for oral cancer and it may include a combination of neo adjuvant chemotherapy, surgery and or radiation therapy. More recently novel molecular target agents have been developed as treatment options. Until now, inhibitors of the epidermal growth factor (EGFR), such as Cetuximab, anti-VEGF (e.g., Bevacizumab), m-TOR inhibitors and other VEGF or EGFR kinase inhibitors and multi-kinase inhibitors represent a curative targeted therapy in combination with radiotherapy and/or chemotherapy.
Several studies have highlighted the fact that there is a lack of awareness about oral cancer, its signs and symptoms among the general population across the globe. Educating the general population about oral cancer is a must to combat mortality and morbidity arising out of it. Considering the risk involved with the consumption of tobacco and alcohol, one should avoid or minimize the use of these in day to day life. HPV vaccination is another option of taking preventive measures for HPV related oral cancer. Finally, clinicians should screen their patients to detect early lesions and educate them about the risk factors that can lead to cancer.
- Giacomo Del Corso GD, Villa A, Tarsitano A et al., Current trends in oral cancer: A review. Cancer Cell & Microenvironment 2016; 3: e1332.
- Lewin F, Norell SE, Johansson H, et al., Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer 1998;82:1367-1375
- Vargas-Ferreira F, Nedel F, Etges A, et al., Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: a brief approach. Braz Dent J 2012;23:586-590.
- Keshavarzi M, Darijani M, Momeni F, et al., Molecular Imaging and oral cancer diagnosis and therapy. J Cell Biochem. 2017 Apr 8. doi: 10.1002/jcb.26042.
- Schmitz S, Ang KK, Vermorken J, et al. Targeted therapies for squamous cell carcinoma of the head and neck: Current knowledge and future directions. Cancer Treat Rev. 2014;40:390-404.