The biologic basis of field cancerization is described in detail in Chap. 1. Oral cancer develops as a multistep, multifocal process. Slaughter et al. [4] suggested the hypothesis of field cancerization based on their observation that serial sectioning of histologic examination of normal appearing mucosa revealed preneoplastic clones of cells away from the primary tumor. These lesions arising in a preconditioned epithelium can progress into new cancer. Based on the spatial and temporal relationship as well as the genetic similarity, Braakhuis et al. [40] proposed three distinct types of local tumor relapse: local recurrence, second primary tumor, and second field tumors (Fig. 6.2). Tumors that are developed less than 2 cm away from the primary tumor and in less than 3 years are considered as local recurrence. If they are genetically identical, it can be considered as true local recurrence. If they are genetically related, it is considered as second field tumors. Those tumors that arise more than 2 cm away or over 3 years after the first tumor, it can be considered as second primary tumor. Based on the genetic similarity to the initial tumor, it can be considered as second field tumor if the tumor is genetically related or as true second primary tumor if they are genetically distinct. The genetic identity of the tumor in this study was carried out by analyzing the pattern of loss of heterozygosity at position 3p12, 3p14, 3p21, 3p24.3, 9p21, 17p11-12, and 17p13.1 [3]. It has been observed that these genetic changes can occur 5–7 cm away from the primary tumor.

Several molecular markers have been employed to identify conditioned mucosa. This includes p53 [6], eIF4E [7], methylation-specific polymerase chain reaction for promoter hypermethylation of O-6-methylguanine-DNA-methyltransferase (MGMT) gene, a DNA repair gene [5]. The clinical application of this technique is limited by the fact that these assays have high false-positive rates as well as it takes over 5 h to process the sample, limiting its intraoperative usage. It was also observed that adjuvant postoperative radiation therapy did not improve recurrence rate in subjects with molecular margin positive tumors [8].

It has been reported that deep positive margin carried a worse prognosis compared to mucosal positive margin. Pattern of invasion of tumor is considered as the primary determinant of probability of deep margin positivity. Brandwein-Gensler et al. [41] studied this relationship in a series of 168 patients with oral squamous cell carcinoma. They modified the existing pattern of invasion grading into five types: type 1, board tumor front; type 2, fingerlike tumor front; type 3, tumor islands of >15 cells; type 4, tumor islands with <15 cells; and type 5, tumor islands with <15 cells more than 1 mm apart. They have observed higher locoregional failure and overall survival in patients with more infiltrative tumor. They have also reported increased incidence of positive margin, perineural invasion, and low lymphocyte infiltration with more infiltrative tumor. Combining these prognostic factors (pattern of invasion, perineural invasion, and lymphocyte infiltration), the authors identified three risk groups. They have observed that while for high-risk group adjuvant postoperative radiotherapy was beneficial, in low-risk groups even with positive margin, there was no additional benefit with adjuvant radiotherapy. This fact was further confirmed by Ch’ng et al. [7]. In a series of 144 patients with close but uninvolved margin (<5 mm), surgery alone obtained locoregional control rate of 91 % and disease-specific survival rate of 84 %. They have also observed stepwise reduction of the disease-specific surgical rate with each addition of high-risk factors of infiltrative pattern of invasion, perineural invasion, depth of invasion, and tumor subsite (buccal mucosa).

Sindhu et al. [9] further evaluate the factors that determine the pattern of invasion and which confer poor treatment outcome. They have hypothesized that the pattern of invasion of oral cancer is determined by the density of cancer stem cells (CSC); the higher the density of cancer stem cells the worse the pattern of invasion (Fig. 6.3). Furthermore, the CSCs have higher migration capacity as well as are resistant to both radiation and chemotherapy. They have observed a close correlation of pattern of invasion and putative cancer stem cell marker CD44 and poor treatment outcome. The CD44 expression also correlated with perineural invasion as well as lower lymphocyte infiltration.

Based on the above findings and randomized clinical trial of adjuvant therapy in head and neck cancer [42], one can formulate an algorithm for adjuvant treatment. This data is summarized in Table 6.1. It is to be noted that level 1 evidence is available only in determining when to give adjuvant chemoradiotherapy. All other recommendations are based on the interpretation of basic science and clinical research data, the art of clinical medicine practice.

Intraoperative pathology consultation (frozen section) is often required for the successful execution of ablative surgery. It is essential for surgeons to know the capabilities and limitations of intraoperative pathologic consultation. The surgeons also should have a good working relationship and effective communication plan with the pathologists.

Common indications for intraoperative consultations are the following:

Frozen section of oral squamous cell carcinoma has a diagnostic accuracy rate (correlation of frozen section with that of permanent section) of about 97 % [22–26, 32]. About 3 % diagnostic error is attributed to improper sampling, technical error, interpretation inaccuracies, and error in communication. It is to be noted that the incidence of false-positive result is about 1 % [56]. Even with this high diagnostic accuracy rate, the frozen section needs to be used judiciously. Chathurvedi et al. [27] have questioned the value addition of frozen section over clinical examination, i.e., can frozen section detect lesions that could not have been detected clinically?

There is now considerable body of literature to substantiate that routine use of frozen section has very limited role in the management of oral squamous cell carcinoma. Chaturvedi et al. [27] in a prospective trial of 145 patients undergoing surgery for head and neck squamous cell carcinoma found that frozen section identified 83 % (n = 64) of 565 mucosal and 104 soft tissue margins as positive of invasive carcinoma. This compromised surgical margin was associated with gross clinically close margin of less than 7 mm. They therefore recommend that there is no value in doing frozen section if the gross clinical margin is more than 7 mm. Similar findings has been reported by many authors demonstrating lack of clinical benefit for routine use of frozen section [23, 26, 32].

Based on the current evidence, Chaturvedi et al. [27] recommended a clinical decision making algorithm (Fig. 6.4). When frozen section is carried out, it is best to be performed from the surgical bed rather than the surgical specimen. The region of where the frozen section was taken should be accurately marked in relation to the primary resection specimen, so that appropriate and accurate intraoperative or postoperative decision can be made.

Traditional method of surgical excision of primary oral cavity squamous cell carcinoma is carried out using the principle of wide local excision with 1 cm normal tissue away from the visible and palpable tumor boarders. Even with apparent negative surgical margin, 30 % of oral cancer fails locally [9]. As stated above, although various biological factors such as pattern of invasion and perineural invasion may contribute to the development of local recurrence, surgical technique may be modified to improve the local disease control rate.

Compartment resection is based on the observation that tumor does not necessarily advance in a concentric fashion but follows pathways of least resistance. This is determined by anatomic structures that either facilitate invasion of tumors such as orientation of muscle fibers, nerve sheath, lymphatics and blood vessels, and structures that offers resistance to tumor invasion such as periosteum and fascia [33, 34]. It is to be noted that ablative surgery that cause discontinuation of a muscle, nerve or blood vessel will have similar functional consequences whether it is remove in part or complete. This formed the basis of compartmental resection that attempted to remove “anatomic compartments” that are involved by cancer. This concept is well established in soft tissue sarcoma surgery of extremities. It has been shown by Azzarelli et al. [35] in a series of 471 patients with extremity sarcoma that compartmental resection yielded significantly better local control rate of 76 % in comparison to 53 % with wide excision. Compartment resection needs to be distinguished from radical Halstedian principle that entails ultraradical excision of tumor and normal tissue of the affected organ disregard to the pattern of invasion of the tumor.

Technique of compartmental resection has been developed for advanced oral tongue [44] and gingivo-buccal carcinoma [31]. In a series of 193 patients with oral tongue carcinoma, Calabrese at al. [45] reported 88.4 % local control rate with compartmental resection in comparison to 71.6 % with conventional surgery. It is to be noted that the concept of compartment resection has application only in moderate to advanced tumors (T2–T4) of oral cavity that involve discernible anatomic units.

Optimal exposure of the tumor is required for intraoperative examination, with maneuvering of instrumentations to achieve three-dimensional excision with uninvolved margins. In addition, the exposure should facilitate optimal reconstruction of the surgical defect. The commonly used methods to oral cavity tumors are peroral, lip split with mandibulotomy, lower cheek flap, visor flap, and upper cheek flap approaches and for advanced gingivo-buccal tumors with skin involvement, extension of the skin incision around the primary tumor excision to the neck (Fig. 6.5). The choice of approach depends on the site and extent of the tumor invasion, the need to remove a part or a segment of maxilla or mandible, dental status, and degree of mouth opening.

Many traditional approaches need to be reevaluated in the context of improved instrumentation, high-speed bone cutting instruments with varying geometry, and improved visualization with fiber optic lighting and endoscopes. These technologic advances have lead to the development of the field of minimally invasive surgery that has revolutionized many surgical fields, limiting morbidity of procedures. In the head and neck region, the impact of which is most apparent in skull base and laryngeal tumors. With the assistance of endoscopes, powered instruments, and lasers, one can safely resect tumors from these critical areas through a natural opening of less than 2 cm in size. It is paradoxical that in the surgical management of oral cavity tumors with the availability of about 4 × 4 cm mouth opening, one often resorts to transcutaneous approaches. It is to be noted that almost all orthognathic surgeries that require osteotomy of maxillofacial skeleton from the mandibular condyle to the symphysis and from Lefort-1 to Lefort-3 are carried out almost exclusively through peroral approaches. Many instruments that are used for craniofacial surgery can be adapted for oral cavity cancer surgery.