**5. Clinical presentations, diagnosis and staging of oral cancer**

#### **5.1 Clinical presentations**

The most common symptoms of oral cancer patients may include ulceration (57.7%), induration (44.3%), and rupture (14.1%) [30]. However, due to the asymptomatic and unspecific signs, more than half of the patients went to a doctor in advanced stages when the discomforts worsen or appearance of new symptoms. In this situation, patients may present with an enlarged lesion, no improvement after the first treatment, onset of pain, inflexible movement of the tongue, discomfort in the mouth, difficulty in speaking and swallowing, bleeding, neck mass, et al.

### **5.2 Diagnosis**

The physical examination of oral cancer is usually performed by inspection and palpation. The examination lasts around several minutes and does not require special equipment or technique. Dentists are the ideal position to perform examination and alarm suspected changes. Clinical investigation include assessment of primary tumor and the surrounded structures, such as deep muscle invasion, fixation to bone, and cranial neuropathies. Once a suspicious lesion is discovered, it is important for clinicians to perform biopsy, which is the gold standard for diagnosis.

An appropriate imaging detection is a complement of physical examination. It provides proper evaluation for patients. Initial examinations of the primary site are usually done with computed tomography (CT) scan and/or magnetic resonance imaging (MRI). CT scan is good at evaluating the larynx, neck nodes and invasion of bone or cartilage. In comparison, MRI is preferred in patients concerning tumor involvement of soft tissue, perivascular, perineural, skull base, and intracranial. In addition, dental films or panoramic X-rays can be used in the assessment of cortical bone involvement and ultrasound (US) can be used to evaluate the metastasis of lymph nodes. As distant metastasis evaluation, FDG-PET/CT works more excellent [31]. However, in case of a concerned specific anatomic site, further contrastenhanced CT and/or MRI should be performed. All the imaging measures mentioned above could help to describe the margins and invasion of the primary tumor, lymph node involvement, local and distant metastasis, thereby providing evidence for clinical TNM (cTNM) staging identification.

#### **5.3 Staging**

Nowadays, more and more studies realize that the malignant behavior of oral cancer is not only determined by tumor size but also invasive depth. Based on this, pathologic examination is further performed to identify pT (an actual measurement of unfixed fresh surgical tumor specimens) and/or pN. As an improvement of the previous oral cancer TNM staging algorithm, the eighth edition of American Joint Committee on Cancer (AJCC) Staging Manual highlights depth of invasion (DOI) for T stages and extranodal extension (ENE) for N stages. These alterations improve the discrimination ability of disease-free survival (DFS) between overall stages as well as T categories [32]. A comparison between the seventh and eighth edition is shown below in **Table 1**.

#### **6. Treatment of oral cancer**

Treatment of oral cancer patients, especially with invasive condition, is best determined by a multidisciplinary team of medical experts, which may include head and neck surgeons, pathologists, radiation oncologists, chemotherapy oncologists, neuroradiologists, reconstructive surgeons, dentists, nurse specialists and nutritionists. Managements include surgical resection, radiotherapy and chemotherapy, depending on anatomic site and size of the primary tumor, lymph node metastasis and distant metastasis, the patient's risk as well as benefit from the treatment, namely a personalized treatment.

#### **6.1 Surgery**

Surgery is the main option for oral cancer patients. There are series of choices: conventional/laser/thermal/robotic surgery, et al. Small tumors located in the anterior part of the oral cavity could be accessed via transoral approach. While for those advanced and/or located in the posterior part of oral cavity, routes of lip-splitting and/or mandibulotomy are suggested. As the first-line treatment strategy, the primary principle of surgery is adequate clearance of tumor and functional preservation (speech, swallowing, deglutition). A positive surgical margin increases the risk of recurrence and generates poor survival outcomes [34]. Thus, complete ablation is demanded, usually a 1-cm macroscopic resection margins around the tumor tissue are suggested for conventional surgery [35–37]. As an adjuvant technique, iodine vital staining supports evidence distinguishing dysplastic or tumorigenic tissues from benign mucosa [38].

However, difficulties of reconstruction come with enough resection margins. The most acceptable reconstruction scheme should take many factors into consideration, including the anatomic site and invasive condition of the primary


#### **Table 1.**

*A comparison of the 7th and 8th edition of AJCC/TNM staging of oral cancer.*

tumor, the general healthy and social economic condition of the patient, and the surgeon team's skills. There are many soft tissue reconstructive techniques such as local flaps, regional pedicled flaps and microvascular free flap, depending on the

defection. For hard tissue defection, autologous bone grafts from the iliac crest, fibula, radius or scapula are common choices.

Elective neck dissection (END) is suggested for all oral cancer patients [37]. It is reported that around 15–30% of cN0 patients have inapparent lymph node invasion (pN) [1], suggesting the importance of prophylactic dissection for N0 patients. Though recent evidence shows that sentinel node biopsy can be a reliable indicator for N0 oral cancer patients, more data is needed to support its function [39]. Additionally, patients with a DOI of more than 4 mm or T2/3/4 stage should undergo neck dissection to improve overall and disease-free survival rate [40].

#### **6.2 Radiotherapy and chemotherapy**

For patients with pathologically positive lymph nodes, occult neck metastasis or existence of extra-capsular spread (ECS), radiotherapy should be initiated. Disadvantages of radiotherapy are many which influence the quality of patients, introducing alteration in skin color, oral cavity mucositis, xerostomia, osteoradionecrosis of the mandible, as well as late toxic symptoms such as dysphagia and dehydration [41]. With the development of intensity-modulated radiotherapy (IMRT), side effects are reduced significantly [42].

Chemotherapy has been applied as an adjuvant approach in oral cancer, especially for patients with locally advanced stage. It can be performed before surgery (known as induction chemotherapy), and also as a combination with radiotherapy (known as chemoradiotherapy) before or after surgery which helps effectively controlling the progression of patients with extracapsular extension in lymph nodes and positive resection margin. As a radiosensitizer, cisplatin is the first-line agent to combine with radiotherapy. What's more, the application of anti-programmed cell death-ligand 1 (PD-L1) antibody is found to improve the prognosis of oral cancer patients with metastasis after chemotherapy using platinum [43].

#### **7. Survival and prognosis of oral cancer**

With the development of diagnosis and adjuvant therapy, a retrospective database study involving 16,020 cases of oral cancer patients between 1973 and 2014 showed that the 3-year survival rate for early stage patients increased from 78% to 92.9%, and for those with late stage disease increased from 51.9% to 70.3% [44]. Another study including 2082 patients in a tertiary cancer care center from 1985 to 2015 found that the 5-year over survival (OS) rate of oral cancer was 64.4% and disease special survival (DSS) rate was 79.3% [45].

Age, surgical margin clearance, vascular and perineural invasion situation, pT and pN are factors affecting prognosis. Among these, lymph node involvement strongly indicates poor prognosis, especially for those with extracapsular spread [46]. Increased tumor size and advanced tumor stage also have their roles on prognosis [47]. However, tumor differentiation, number of metastasis nodes, ethnicity are found to have no relationship with prognosis. Due to variation in the geography and studied population, more evidence is needed.

#### **8. Screening of oral cancer**

More than 50% of oral cancer patients are diagnosed at the state of regional or distant metastasis. Thus, a proper screening is urgently needed for earlier detection and prevention. A primary screening for oral cancer is visual inspection combined

#### *Oral Cancer DOI: http://dx.doi.org/10.5772/intechopen.97330*

with palpation. Any abnormality that with a history longer than fourteen days should be reevaluated, and a tissue biopsy is required. There are other adjunctive techniques providing subjective interpretations, including toluidine blue staining, brush cytopathology, salivary diagnosis, tissue autofluorescence and chemiluminescence [48]. Alteration of the oral microbial community has its role in predicting oral cancer too, such as the carcinogenic Porphyromonas gingivalis and F nucleatum [49]. Although there is increasing clues showing HPV infection in oral cancer, no screening project has been approved by the U.S. Food and Drug Administration (FDA). Furthermore, a recommendation from the U.S. Preventive Services Task Force (USPSTF) suggested that more evidence is needed to access the value of screening for oral cancer between benefits and drawbacks [50].
