Epidermoid Carcinoma Of Oral Cavity (Squamous Cell Carcinoma)

A malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin or the presence of intracellular bridges. Inhaled or chewed tobacco is equally addictive and harmful and used daily by over 1 billion people. In addition to increased rates of coronary artery disease, stroke, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease and lung cancers, tobacco are the leading preventable cause of oral cavity squamous cell carcinoma. In addition to tobacco, consumption and abuse of alcohol, and betel nut quid significantly contribute to the burden of oral cavity squamous cell carcinoma. Dental visits are excellent opportunities to identify primary lesions in the oral cavity. This review highlights relevant anatomy, epidemiology, pathogenesis, evaluation and treatment options for oral cavity squamous cell carcinoma. I. Epidemiology: In India, oral cancer constitutes 9.8% of an estimated 644,600 incident cancer cases in 1992, ranks first among all cancer cases in males and the third most common among females. On the basis of cancer registry data, it is estimated that annually 75,000 to 80,000 new oral cancer cases develop in India. Worldwide, approximately 275,000 oral cavity malignancies are diagnosed each year and the predominant malignancy is squamous cell carcinoma [1,2]. In Sri Lanka, India, Pakistan and Bangladesh, nearly a quarter of total cancer diagnoses are oral cavity squamous cell carcinoma. In western countries, oral cavity squamous cell carcinoma represents approximately 3% of new cancer diagnoses annually. Globally, oral cavity squamous cell carcinoma primarily affects males (1.5:1) [3]. Mortality rate lowest for lip cancer (. 04 per 100,000) and highest for tongue (. 7 per 100,000). More than 90% occur in the patients over 45yrs of age. Anatomy: Anatomical sites and subsites: Lip (ICD CODING) 1. External upper lip 2. External lower lip 3. Commissures Oral cavity 1. Buccal mucosa a. mucosa of upper and lower lips b. Cheek mucosa c. Retromolar area d. Buccoalveolar Sulci 2. Upper alveolus and gingiva 3. Lower alveolus and gingiva 4. Hard palate 5. Tongue 6. Floor of mouth. Pathogenesis: Nicotine is rapidly absorbed through the oral cavity mucosa or pulmonary epithelium and provides individuals with increased energy, reduced anxiety, reduced stress and appetite suppression. Within 30 minutes, abstinence results in somatic symptoms such as bradycardia, gastrointestinal distress, increased appetite as well as depressed mood, irritability, anxiety, and frustration [4,5]. The highly rewarding effects of tobacco along with the negative effects of cessation make prolonged abstinence from tobacco the exception rather than the rule, even for individuals who are motivated to quit Epidermoid Carcinoma Of Oral Cavity (Squamous Cell Carcinoma) DOI: 10.9790/0853-14426469 www.iosrjournals.org 65 | Page Tobacco use has been demonstrated to increase rates of coronary artery disease, stroke, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease and a variety of cancers. While over 60 carcinogenic substances have been identified in tobacco smoke, the levels of known carcinogens are generally lower in smokeless tobacco; however, nitrosamines 4-(methylni-trosamino) -1-(3pyridyl) -1-butanone (NNK) and N′-Nitrosonornicotine (NNN) are present in both smokeless and inhaled tobacco products. NNK and NNN form covalent bonds with genomic DNA, resulting in genomic instability and are thought to be the primary mediators of malignant transformation. The oral cavity is the initial conduit for tobacco, and also serves as the entryway for alcoholic beverages. The mechanism of alcohol addiction is complex; however, it is well established that ethanol directly affects N-methyl-D-aspartate receptor (NMDA), γ-aminobutyric acid type A GABAA and 5hydroxytryptamine 3 (serotonin; 5-HT3) receptors resulting in addiction [16]. Heavy consumption of alcohol increases the risk of oral cavity cancer 2-3 times, and alcohol use is implicated in 15% of oral cancers [5]. At least part of the carcinogenic effects of alcohol are mediated by the initial metabolite acetaldehyde, which forms DNA adducts And results in aberrant DNA methylation patterns [6,7]. Additionally, alcohol may lead to malignant transformation by acting as a solvent to increase permeability of tobacco carcinogens, impairing immunity and causing nutritional deficiencies [8]. Betel quid is the 4th most commonly consumed psychoactive drug after caffeine, alcohol, and nicotine. While the betel quid has regional variation, a typical preparation consists of betel leaves (Piper betel) wrapped around the fruit of the Areca catechu tree [5]. The principal psychoactive and addictive components of betel quid are Arecoline and arecaidine, which act as muscarinic agonists and GABA antagonists respectively. While some regions incorporate tobacco into betel quid, there is strong evidence that betel quid alone increases the risk of cancer by up to 9 fold. The carcinogenic compounds have been less clearly defined than in tobacco and alcohol, but NNK, NNN, and reactive oxygen species are thought to be the main drivers of oncogenesis [9,10]. Carcinogenesis is thought to be driven by expression of three of these proteins, E5, E6 and E7, which alter the host cell cycle. HPV associated oropharyngeal squamous cell carcinoma has been associated with improved outcomes, resulting in efforts to de-intensify treatment. However, the prognosis of HPV positive oral cavity squamous cell carcinoma has been shown to be worse than HPV negative tumors [11,12,13]. A. Patient with beefy red lesions consistent with erythroplakia on lateral aspect of oral tongue. B. Grossly the lesion appears beefy red consistent with erythroplakia but pathology demonstrates carcinoma in situ. Epidermoid Carcinoma Of Oral Cavity (Squamous Cell Carcinoma) DOI: 10.9790/0853-14426469 www.iosrjournals.org 66 | Page Evaluation & Differential Diagnosis Regular dental visits are an ideal time for identification of suspicious lesions in the oral cavity. Oral cavity squamous cell carcinoma can present as an innocuous rough patch, but more commonly presents as leukoplakia or erythroplakia. Erythroplakia is generally described as red velvety plaques, which cannot be characterized clinically or pathologically as any other recognizable condition (Figure 2) [14]. Reports of the malignant potential for leukoplakia vary widely in the literature; however, transformation rates of 1% per year are generally cited [15]. In contrast to the low malignant potential of leukoplakia, erythroplakia has a high propensity to degenerate into malignancy [16] and we recommend routine excisional biopsy. While we often advocate for an excisional biopsy of leukoplakia, if a dental amalgam or other cause of chronic irritation can be identified and remedied, follow-up for resolution of the lesion is reasonable. For low risk patients without smoking history, hemoptysis, weight loss, or obvious, palpable lymphadenopathy, a chest X-ray is a reasonable alternative. Magnetic Resonance Imaging (MRI) with contrast is also helpful to assess soft tissue involvement, especially of tumors of the oral tongue and where dental artifact limits the quality of the study. Patients will likely undergo formal endoscopy for staging and assessment of synchronous tumors. While the role of panendoscopy (laryngoscopy, bronchoscopy and esophagoscopy) has been called into question given low rates of metachronous lesions, improvements in computed tomography and 18F-Fluoro-2deoxy-D-glucose positron emission tomography-computed tomography, we still routinely perform panendoscopy in all patients taken to the operating room for formal excision of malignant lesions [17,18]. While squamous cell carcinoma accounts for over 90% of oral cavity malignancies, other pathologies of minor salivary glands, major salivary glands, sarcomas, lymphomas, mucosal melanoma, nerve sheath tumors and metastases from other sites have been identified in the oral cavity [19,20]. The behaviors of these malignancies are highly variable, and given their rarity, warrant immediate referral to the multidisciplinary team for further evaluation and treatment. A large exophytic lesion on right buccal mucosa. Imaging is a diagnostic adjuvant for assessing the patient. A. Computed tomography with contrast demonstrates a squamous cell carcinoma of alveolar ridge eroding maxillary bone (arrow) B. A level IV, 2 cm lymph node (*) is noted to be compressing the internal jugular vein by computed tomography with contrast. C. T1 weighted magnetic resonance image provides robust localization of the extent of an oral tongue squamous cell carcinoma. Epidermoid Carcinoma Of Oral Cavity (Squamous Cell Carcinoma) DOI: 10.9790/0853-14426469 www.iosrjournals.org 67 | Page D. F-Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography identifies an avid subcarinal lymph node (triangle) and right hilar lymph nodes (arrow). Staging The American Joint Committee on Cancer (AJCC) has detailed a comprehensive staging system for oral cavity squamous cell carcinoma using the standard Tumor, Nodes and Metastasis (TNM) classification system. An overview of the staging system is presented in Table 2 and Table 3. In addition to TNM staging, histologic tumor depth has been shown to be an important prognostic variable. Tumors with less than 2 mm as compared to tumors with more than 2 mm of invasion have 13% and 46% chance of nodal metastasis at diagnosis. Furthermore, their respective rates of disease-free survival is 95% and 85% respectively at 2 years [21]. Primary Site Treatment Management options include radiation, chemotherapy, surgery, or a combination of these modalities. Despite a lack of evidence from randomized control trials, stage I and II oral cavity squamous cell carcinoma can be treated with single modality radiation or surgery with similar efficacy. In our practice, primary radiation therapy is reserved for poor surgical candidates and we consider primary surgery with possible adjuvant radiation therapy the standard of care. Primary surgical resection spares patients the long-term morbidity associated with radiation therapy such as xerostomia, osteoradionecrosis, dysgeusia, dysphagia, and dental caries. The majority of oral cavity T1 and T2 tumors can be resected through a transoral approach. For larger or posterior tumors, lip split approaches with or without mandibulotomy may be necessary to gain adequate exposure. For larger tumors, T3 or T4, tumors with close margins after resection, bone invasion, deeper depth of invasion, and multiple lymph node involvement, adjuvant postoperative radiation is routinely performed[22]. Treatment of the Neck The oral cavity has a rich lymphatic network that results in general trends but not rules regarding the location of nodal metastasis. For treatment and staging purposes the nodal basins of the neck are anatomically Epidermoid Carcinoma Of Oral Cavity (Squamous Cell Carcinoma) DOI: 10.9790/0853-14426469 www.iosrjournals.org 68 | Page broken down into 7 levels (Table 4). In a large study of over 1000 patients with clinical nodal metastasis, oral tongue, floor of mouth, and retromolar trigone primary site tumors metastasized primarily to ipsilateral levels I, II, and III [23]. Soft palate lesions were slightly different with metastases primarily to levels I and II, with a greater than 10% rate of metastasis to the contralateral side in level I[23]. The importance of resection of nodal metastatic disease in the treatment of head and neck cancers was recognized in the early 1900’s by George Crile who subsequently developed the radical neck dissection, which removed all of the lymphatic tissue from the lateral neck and was further refined by Hayes Martin in the 1950’s. The clinical importance of the neck is paramount. The presence of positive lymph nodes with extracapsular spread is the single-most important determinant of prognosis, cutting survival in half when present. Surveillance The majority, up to 80%, of recurrences occur within the first 4 years[24]. Therefore, we routinely follow patients every 1-2 months for the first year after treatment followed by every 3-4 months in the 2nd year followed by every 6 months from years 3-5. Five years after the completion of treatment, patients should undergo lifelong yearly follow-up. Besides identifying recurrent disease, every encounter with medical and dental providers should emphasize the importance of abstaining from tobacco, ethanol, and betel quid. It is well established that patients who continue these highly addictive habits have worse local control rates and outcomes in general[25]. II. Conclusions Worldwide, oral cavity squamous cell carcinoma causes significant mortality and morbidity. As the majority of cases worldwide are linked to consumption of alcohol, tobacco, and betel quid, public health efforts aimed at cessation and discouraging initial use of these addictive substances will have the greatest impact in decreasing the burden of this disease. If trends that have been seen in the United States continue worldwide with public health campaigns, the makeup of oral cavity squamous cell carcinoma will be drastically different in 50 years and suggests that we need additional research efforts into the treatment and prevention of HPV associated oral cavity and oropharyngeal squamous cell carcinoma.