Gingivobuccal Carcinoma

  • Squamous cell carcinoma (SCC) of the oral cavity:
    • Ranks as the 13th most common cancer in the world and 7th most frequent in males
    • There is not only a marked variation in the incidence and mortality from oral cancer between various countries but also between ethnic groups and regions of one country:
      • This is primarily attributable to variations in the prevalence of major risk factors between populations:
        • However, other dietary and genetic influences may also contribute
  • The lower gingivobuccal complex:
    • Is comprised of buccal mucosa, gingivobuccal sulcus, lower gingiva and retromolar trigone
    • It is the most common site for oral cancer in the Indian subcontinent due:
      • To the habit of chewing tobacco
  • The goal of evaluating a patient with gingivobuccal complex cancer:
    • Is to assess the extent of disease and to define the tumour type histologically
    • Patients usually present with:
      • A persistent ulcer or an exophytic growth in the gingivobuccal complex
      • Loosening of teeth
      • Ill-fitting denture
      • Trismus
      • Pain:
        • Is a late feature
    • Patients with advanced disease present with:
      • Orocutaneous fistula
      • Severe trismus
      • Lymph node metastasis
    • Many patients have associated premalignant lesions like:
      • Leukoplakia and erythroplakia or premalignant condition like submucous fibrosis
    • An asymptomatic lesion, with a history of tobacco and / or alcohol consumption:
      • Should raise suspicion of oral cancer and biopsy should be done.
  • Examination assesses the extent of involvement of important structures such as:
    • Mandible, floor of the mouth musculature and cervical nodes
    • The presence of trismus:
      • May suggest deep invasion
      • It is important to determine whether this trismus is due to:
        • Associated submucous fibrosis or malignant disease
    • The clinician should evaluate any medical and nutritional problems
      • Common problems in patients with cancer of the oral cavity are:
        • Hepatic disease, pulmonary disease and malnutrition
  • Knowledge of the mode of spread of gingivobuccal complex cancer;
    • Is important for developing a rational therapeutic approach
    • Local spread to adjacent structures:
      • May lead to invasion of the underlying soft tissue, muscles, bone and neurovascular structures
    • Gingivobuccal complex cancer extends:
      • Along surface mucosa and the submucosal soft tissue:
        • To approach the buccal or labial gingiva
      • From this point onwards:
        • The tumour does not extend directly through the intact periosteum and cortical bone towards the cancellous part:
          • Because the periosteum acts as a significant protective barrier
      • Instead:
        • The tumor advances along the attached gingiva towards the alveolus
      • Subsequently:
        • The mandible is involved by infiltration through the dental sockets or the dental pores (in edentulous patients) on the alveolar ridge:
          • These cells proceed along the root of the tooth into the cancellous part of the mandible and then along the mandibular canal:
            • This understanding has led to the development of mandible-sparing, surgical resections
    • Cervical lymph nodes:
      • Are the most commonly involved metastatic site
    • The neck has been divided into five nodal levels:
      • For planning treatment of gingivobuccal complex cancer
  • The gingivobuccal complex has a predictable lymphatic drainage:
    • The first echelon lymph nodes are in the:
      • Supraomohyoid triangle of neck:
        • Levels I, II, III
    • Spread to lymph nodes in posterior triangle:
      • In the absence of metastasis at other levels:
        • Is rare
    • Skip metastasis from gingivobuccal complex carcinomas:
      • Are rare
    • Distant metastasis at the time of initial diagnosis is exceedingly rare:
      • When it does occur it is to lung and bones
  • Biopsy of the lesion is mandatory before treatment:
    • Often, this can be done under local anaesthesia
    • The biopsy should be deep and encompass a portion of the tumour as well as adjacent normal appearing mucosa
    • Superficial biopsies are inconclusive and yield negative results
    • In suspected verrucous carcinomas:
      • Where the basement membrane is intact:
        • A deep biopsy is mandatory to reach a diagnosis
  • Imaging work-up depends on the extent of the disease:
    • Patients with early lesions do not need an extensive evaluation:
      • An orthopantomogram or oblique radiograph of the mandible is a cost-effective initial investigation to assess mandibular involvement
    • The accuracy of clinical examination, peroperative periosteal stripping and imaging techniques have been compared:
      • Clinical examination alone was not shown to be accurate:
        • But periosteal stripping at the time of resection was extremely accurate
      • No single imaging technique will accurately predict mandibular invasion:
        • However, a combination of orthopantomogram and bone scintigraphy is recommended in early invasion
        • Magnetic resonance imaging (MRI) is more sensitive than computerised tomography (CT) for mandibular invasion
        • CT scanning gives additional information regarding the extent of mandibular involvement, malignant infiltration and cervical nodal disease
        • MRI can be used to determine soft tissue and perineural involvement
        • However, all patients do not need CT scan or MRI:
          • These are especially indicated in patients with large lesions having trismus and lesions abutting the mandible where marginal mandibulectomy is being planned
        • It is also used to evaluate patients with a clinically negative neck or those with large nodes for presence of carotid involvement
        • Ultrasound guided fine needle aspiration cytology (FNAC) has the highest accuracy in diagnosing cervical nodal metastasis in the clinically negative neck compared to ultrasonography, CT scan and MRI:
          • However, none of the imaging methods can determine occult metastatic nodal disease
    • In view of the risk of multifocal changes:
      • Endoscopic evaluation (panendoscopy) of the upper aerodigestive tract is recommended to evaluate the presence of second primaries:
        • Direct laryngoscopy, bronchoscopy, esophagoscopy and examination under general anesthesia may be done for accurate assessment of the disease and the upper aerodigestive tract
    • Depending on the specific site in the gingivobuccal complex (alveolus, gingivobuccal sulcus or buccal mucosa alone):
      • The extent of the primary tumor and the status of lymph nodes:
        • The treatment of these cancers may be by surgery or radiation therapy used alone or in combination, with or without chemotherapy
    • Early lesions (T1, T2) can be effectively treated with either surgery or radiation as a single modality:
      • Certain factors influence this decision:
        • For example, in the presence of associated submucous fibrosis:
          • Surgery is preferable to radiation therapy
        • Lesions located in lower gingivobuccal sulcus or involving mandible are usually not treated with radiation:
          • Because of proximity to bone and chances of osteo-radionecrosis
      • Advanced lesions require a combined modality treatment
  • Treatment of gingivobuccal complex cancer:
    • Is primarily surgical:
      • The aim of surgical treatment is to excise the entire primary lesion with clear margins (1 to 2 cm) three-dimensionally, and also effectively treat the regional lymph nodes
      • This ablative surgery is followed by primary reconstruction:
        • To provide rapid healing, restore function and appearance and thereby improve patient’s quality of life
      • These lesions are resected either by an upper or lower cheek flap with a lip split, visor flap or per-orally:
        • Depending upon the size and location of the primary
      • These cancers often abut or involve the mandible
      • Most of these cancers are not amenable to per-oral resection:
        • Owing to inadequate access:
          • Which may jeopardise the oncological resection
      • Per-oral resection is possible in:
        • Small lesions (usually, 2 cm or less), situated anteriorly, with no or minimal mandibular involvement, and with good mouth opening
      • Radical ablative surgery is followed by reconstructive surgery:
        • Surgical defects may be reconstructed by primary closure, skin graft, locoregional flaps or free tissue transfer from different sites
      • The decision to resect the mandible as part of the management of oral cancer:
        • Should be taken on the evidence of clinical examination, periosteal stripping and at least two imaging techniques that complement each other in terms of specificity and sensitivity
      • Lesions that directly invade the bone:
        • Should undergo a segmental or hemi-mandibulectomy
      • Resection of the posterior part of the body or ramus of mandible leaves very little aesthetic deformity, but there is always functional compromise with segmental resection of any part of mandible
      • Resection of anterior arch of mandible:
        • Results in significant functional and cosmetic deformity and immediate reconstruction should be done by an osteomyocutaneous flap or composite free tissue transfer
          • If immediate reconstruction is not feasible or desirable, the mandibular stirrups should be immobilised by internal, external or interdental fixatio
          • Heavy reconstruction plates may also be used in this situation.
    • Mandibular sparing techniques like marginal mandibulectomy have gained popularity for lesions with no, or minimal, cortical mandibular invasion:
      • Marginal mandibulectomy has been used for along time in cancer of the floor of the mouth and can also be used for cancers of gingivobuccal complex
      • Mandibular continuity is maintained and a much better cosmetic and functional end result is achieved with marginal mandibulectomy:
        • At least, a 1-cm thick segment of bone must be left inferiorily after a marginal mandibulectomy
      • Marginal mandibulectomy is contraindicated in patients with:
        • Gross clinical and radiological involvement of mandible
        • Invasion of mandibular canal by cancer
        • In deeply infiltrating lesions of gingivobuccal sulcus where there is paramandibular infiltration:
          • As the margin of resection may pass through infiltrated paramandibular tissue
        • It is also contraindicated in previously irradiated mandible
        • Reduced vertical height of the bone in an edentulous mandible is a relative contraindication for marginal mandibulectomy
        • Marginal mandibulectomy is also usually not done in lesions of the retromolar trigone as clearance of pterygoid region is possible only if ascending ramus of the mandible is resected:
          • However, some studies have also reported satisfactory results of marginal mandibulectomy in lesions of the retromolar trigone
        • Results of marginal mandibulectomy for gingivobuccal complex carcinoma show an:
          • Overall local recurrence-free survival rate of 79% and 70% at 2 and 5 years, respectively
        • Other studies have also demonstrated the oncological safety of marginal mandibulectomy in carefully selected patients with oral cancers
  • The management of neck for gingivobuccal complex cancers:
    • Depends on whether the neck is clinically node-negative or node-positive
    • In patients with clinically positive lymph nodes (Nl, N2, N3):
      • Radical neck dissection (RND) has been the gold standard
    • However, there is mounting evidence that RND should not be the only therapeutic option for the clinically positive neck:
      • In patients with clinical N1 disease and selected N2 disease:
        • A modified radical neck dissection may be done for better cosmetic and functional results
        • Preservation of the spinal accessory nerve, internal jugular vein (IJV) and sternocleidomastoid muscle:
          • Is done in the form of a modified radial neck dissection (MRND)
  • RND, however, is still appropriate for patients with:
    • Massive lymphadenopathy (N3 disease)
    • Multiple positive nodes involving the spinal accessory nerve and / or the IJV
    • Residual or recurrent neck disease after radiotherapy
    • Gross extranodal spread
  • A supraomohyoid neck dissection (SOHND):
    • Clearance of level I, II and III nodes plus postoperative radiation therapy has been advocated by a few authors for N1, level I disease:
      • There are still no prospective, randomised trials comparing SOHND with RND / MRND in clinically positive neck and it is unlikely that studies large enough to answer this question will be carried out in the future
  • Nodal spread can occur to both sides of neck:
    • Especially in lesions:
      • Close to mid-line
    • In patients with bilateral nodal metastasis:
      • A bilateral neck dissection with preservation of IJV on at least one side (the less affected side) is indicated:
        • An alternative to this is to do a staged RND:
          • The IJV resection is done on both the sides with an interval of 4 weeks between them
  • Occult nodal metastatic disease:
    • Is present in 5% to 26% of gingivobuccal complex cancers:
      • Depending on the T-status and grade
    • Management of the clinically negative is thus an important issue:
      • Patients with T1 / T2 cancers (low risk, less than 20% risk of nodal metastasis):
        • Do not require elective neck treatment
      • SOHND should be performed in patients with:
        • T3 / T4 primary (high risk, greater than 20% risk of nodal metastasis)
        • If entering the neck to resect the primary
        • Short-necked individuals:
          • Who require a bulky flap for oral reconstruction:
            • To create space in neck
        • Patients who are unreliable for follow-up
      • Patients who are found to have pathologically positive neck nodes after SOHND:
        • Should receive additional treatment
      • If detected positive intra-operatively (on frozen section):
        • Then SOHND should be changed to RND or MRND
      • Patients with positive lymph nodes, diagnosed on histopathology following SOHND:
        • Should either undergo RND / MRND or postoperative radiotherapy
      • Patients with a single positive, level I node only, without extra-capsular spread:
        • May not need additional treatment
      • A randomized trial comparing SOHND with comprehensive neck dissection in patients with clinically negative nodes:
        • Found no difference in the regional control and overall survival rates between the two groups:
          • However, SOHND alone is inadequate treatment for patients with pathologically confirmed or clinically positive nodes
      • Patients undergoing MRND need adjuvant radiation therapy to the neck if N2 disease is present
        • Adjuvant radiation provides good regional control
      • The role of ultrasound-guided FNAC of the N0 neck in the decision for elective neck dissection has been reported:
        • However, its application to gingivobuccal complex cancers in particular is uncertain
    • Recently, lymphatic mapping with sentinel lymph node biopsy has been used in N0 oral cancer patients but further refinement of technique and larger studies are needed before this can be recommended as standard treatment
  • Radiation therapy and surgery:
    • Have equal success in controlling early lesions of the oral cavity
    • Radiation is given either as:
      • External beam, brachytherapy or acombination of both
    • For gingivobuccal complex cancers:
      • Radiotherapy is usually not the preferred modality of treatment for early cancers (T1, T2):
        • Due to the close proximity of the tumour to bone and risk of radionecrosis
      • Radiotherapy is used for treatment of early lesions of buccal mucosa and gingivobuccal sulcus:
        • Where the patient is not medically fit or is unwilling for surgery
      • It is also used as an adjuvant treatment for the primary tumor in patients with histologically positive margins on resection:
        • And has been shown to decrease the local recurrence rate
    • In patients with advanced lesions (T3, T4):
      • A combination of surgery and radiation therapy provides a better chance of cure than either modality alone
      • The 3-year survival for stages III and IV disease treated with radiation therapy or surgery alone:
        • Is 41% and 15%, respectively
      • These rates increase to 60% and 35%, respectively:
        • When surgery is combined with postoperative radiation therapy
      • In a randomized trial, Mishra et al:
        • Have reported a significant improvement in disease-free survival in patients with T3 / T4 carcinoma of the buccal mucosa
      • Postoperative radiation therapy is indicated in all patients with:
        • T3 primary tumors
        • T4 primary tumors
        • Patients with positive or close surgical margins
        • Pathologically positive lymph nodes after SOHND
        • Two or more positive lymph nodes after RND / MRND
        • Lymph nodes showing extracapsular spread
      • There is evidence for the use of adjuvant concurrent chemoradiotherapy:
        • In patients of head and neck cancers with poor prognostic factors
    • Definitive radiation or concurrent chemoradiotherapy:
      • Is used in advanced (stage III / IV) disease, if the disease is inoperable or the patient is unfit or unwilling for surgery
    • Concurrent chemoradiotherapy:
      • Has evolved as the standard of care for such locally advanced head and neck cancers
    • The toxicity of concurrent chemoradiotherapy is more than radiation therapy alone and requires aggressive supportive measures. However, evidence for use of concurrent chemoradiotherapy for oral cavity subsite is sparse.41
  • In clinically node-negative neck cancer, elective neck irradiation is done if the primary is being treated with radiation therapy.

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