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Oral Cancer

Oral Cavity Cancer Revision Notes

Introduction

  • Oral cavity extends from the mucosal surface of the lips to the junction of the hard and soft palate.
    • Does not include the soft palate, uvula, or tonsils (part of the oropharynx).
  • Eighth most common cancer worldwide.
    • Approximately 350,000 cases annually.
  • Despite advances, morbidity and prognosis remain largely unchanged.

Epidemiology

Incidence

  • 350,000 new cases per year globally.
  • Squamous cell carcinomas (SCCs) account for the vast majority.
  • Age-standardised ratio (2015):
    • Men: 5.8 per 100,000
    • Women: 2.3 per 100,000
  • Two-thirds of cases occur in low-income countries.
    • Half of these in South Asia (e.g., India has 100,000 new cases annually).
  • High-incidence areas:
    • South East Asia
    • Papua New Guinea
    • Parts of Western Europe (Portugal, France)
    • Parts of Eastern Europe (Slovakia, Hungary)
    • Latin America (Brazil)
  • Age factors:
    • Incidence increases with age; most cases in those over 50 years.
    • Mean age at presentation: 62 years.
    • Increasing cases in patients 45 years or younger without traditional risk factors.
  • Survival rates:
    • Early-stage cancers: 5-year survival rate of 80%.
    • Overall: 5-year survival remains at 50%.
    • In South Asia, often below 50%; reported as 35% in India.

Regional Variations

  • India:
    • Oral cancer accounts for over one-third of all cancers.
    • Age-adjusted incidence rate: 20 per 100,000.
    • Buccogingival/retromolar area cancers make up over 40%.
    • High prevalence due to betel quid/gutka and smokeless tobacco use.
  • Europe:
    • Significant variation between Eastern and Western Europe.
    • Eastern Europe (e.g., Hungary) has some of the highest incidence rates.
    • High-risk sites include the lateral border of the tongue and floor of the mouth.
  • USA:
    • Age-adjusted rate: 11.2 per 100,000 per year.
    • Deaths: 2.5 per 100,000 per year.

Risk Factors

  • Established risk factors:
    • Tobacco (smoking and smokeless)
    • Alcohol
    • Betel quid (areca nut, catechu, slaked lime wrapped in a piper betel leaf)
    • Doseā€“response relationship: Higher exposure increases risk.
  • Human papillomavirus (HPV):
    • Accounts for only ~5% of oral cavity SCCs.
    • Contrasts with oropharyngeal SCCs (50ā€“70% HPV-positive).
    • HPV-positive SCC does not confer a survival advantage in the oral cavity.
  • Other risk factors:
    • Previous radiation exposure
    • Chronic infections
    • Immunosuppression
    • Hereditary conditions:
      • Fanconi anaemia
      • Liā€“Fraumeni syndrome

Summary of Risk Factors

  • Smoking
  • Alcohol
  • Betel quid
  • HPV infection
  • Hereditary conditions
  • Immunosuppression
  • Chronic infections
  • Potentially/premalignant lesions

Premalignant Lesions

  • Potentially malignant lesions are mucosal abnormalities from which oral cancer can arise.
  • Types of lesions:
    • Leukoplakia:
      • White patch or plaque that cannot be rubbed off.
      • Cannot be clinically or pathologically characterized as any other condition.
    • Erythroplakia:
      • Bright red velvety plaque.
      • Higher risk of malignant transformation than leukoplakia.
    • Erythroleukoplakia (Speckled Leukoplakia):
      • Combination of leukoplakia and erythroplakia.
      • Carries the greatest risk for malignant change.
    • Proliferative Verrucous Leukoplakia (PVL):
      • Persistent, widespread white plaques.
      • High risk of malignant transformation.
      • Often recurs after excision.
    • Oral Submucous Fibrosis:
      • Chronic, progressive scarring of the oral mucosa.
      • Associated with areca nut chewing.
      • Leads to stiffness and restricted mouth opening.
      • Increased risk of malignant transformation.
    • Oral Lichen Planus:
      • Chronic inflammatory condition.
      • Presents as white, lacy patches or erosive lesions.
      • Potential for malignant transformation.
    • Lupus Erythematosus:
      • Autoimmune disease affecting the oral mucosa.
      • Lesions may mimic lichen planus.
      • Risk of malignant change.
    • Inherited conditions:
      • Epidermolysis Bullosa:
        • Genetic disorders causing fragile skin and mucous membranes.
        • Repeated blistering leads to scarring.
        • Increased risk of squamous cell carcinoma.
      • Dyskeratosis Congenita:
        • Rare inherited disorder.
        • Features include abnormal skin pigmentation, nail dystrophy, oral leukoplakia.
        • High risk of developing oral cancer.
  • Management challenges:
    • Inconsistent nomenclature internationally.
    • Unclear natural history of lesions.
  • Malignant transformation rates vary widely (0.13% to 34%).
  • Risk factors for malignant change:
    • Female sex
    • Lesion size >200 mmĀ²
    • Non-homogeneous appearance
    • Non-smoker status
    • Multiple lesions
    • High-risk locations (e.g., lateral tongue, floor of mouth)
  • Surgical removal does not eliminate risk; ongoing surveillance is essential.

Molecular Biology

  • Genetic mutations in HPV-negative head and neck cancers:
    • p53 mutations in 83% of cases.
    • CDKN2A alterations in 57%.
  • HPV-positive tumors (common in oropharynx) retain wild-type p53.
  • Current treatments are not based on genetic profiling.

Staging

  • Purpose:
    • Document tumor size, location, and extent.
    • Formulate treatment plans.
    • Discuss prognosis.
    • Facilitate outcome comparisons.
  • Eighth edition AJCC/UICC TNM staging includes:
    • Depth of invasion (DOI) in T staging.
    • Extranodal extension (ENE) in nodal staging.

T Stage (Tumor)

  • T1: Tumor ā‰¤2 cm and DOI ā‰¤5 mm.
  • T2:
    • Tumor ā‰¤2 cm with DOI >5 mm and ā‰¤10 mm, or
    • Tumor >2 cm but ā‰¤4 cm with DOI ā‰¤10 mm.
  • T3:
    • Tumor >4 cm, or
    • Any tumor with DOI >10 mm.
  • T4a: Moderately advanced local disease.
    • Lip: Invasion through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face.
    • Oral cavity: Invasion into adjacent structures (cortical bone of mandible/maxilla, maxillary sinus, skin of face).
  • T4b: Very advanced local disease.
    • Invasion into masticator space, pterygoid plates, skull base, or encasing internal carotid artery.

N Stage (Nodes)

  • Lymph node levels I-V define neck regions.
  • OCSCC metastasis patterns:
    • Commonly spreads to levels I, II, III.
    • Skip metastases to levels III or IV can occur, especially with oral tongue cancers.
  • Extranodal Extension (ENE):
    • Occurs when cancer extends beyond the lymph node capsule.
    • Associated with a worse prognosis.
    • Now included in nodal staging.

M Stage (Metastasis)

  • M0: No distant metastasis.
  • M1: Distant metastasis present.
  • Presence of distant metastasis classifies cancer as Stage IVC (advanced disease).

Prognostic Stage Groupings

  • Stage I: T1 N0 M0
  • Stage II: T2 N0 M0
  • Stage III: T3 N0 M0 or T1-3 N1 M0
  • Stage IVA: T4a N0-1 M0 or T1-4a N2 M0
  • Stage IVB: Any T N3 M0 or T4b Any N M0
  • Stage IVC: Any T Any N M1

Pathology of Oral Cancers

  • Over 95% are squamous cell carcinomas (SCCs).
  • Histological parameters:
    • Histological type
    • Tumor grade/differentiation
    • Pattern of invasion
    • Tumor thickness and depth of invasion
    • Perineural invasion (PNI)
    • Lymphovascular invasion (LVI)
    • Bone involvement
    • Nodal metastases

Histological Type

  • Conventional squamous-type carcinomas are most common.
  • Less common variants:
    • Papillary SCC
    • Adenosquamous carcinoma
    • Acantholytic SCC
    • Basaloid SCC
    • Spindle cell carcinoma
    • Verrucous carcinoma
    • Carcinoma cuniculatum

Tumor Grade (Differentiation)

  • WHO grading system:
    • G1: Well-differentiated (resembles normal tissue)
    • G2: Moderately differentiated
    • G3: Poorly differentiated (less resemblance to normal tissue)
  • Poorly differentiated tumors are more aggressive and have a worse prognosis.

Pattern of Invasion

  • Advancing front of the tumor is assessed.
  • Patterns:
    • Cohesive: Tumor cells invade in a unified front.
    • Non-cohesive: Tumor cells invade individually or in small clusters.
  • Prognostic significance: Non-cohesive patterns are associated with higher aggressiveness.

Tumor Thickness and Depth of Invasion

  • Tumor thickness: Distance from tumor surface to deepest point.
  • Depth of invasion (DOI):
    • Measured from the basement membrane of adjacent normal mucosa to the deepest point of invasion.
    • Greater prognostic importance than tumor thickness.
    • Higher DOI correlates with increased risk of metastasis.

Perineural Invasion (PNI)

  • Definition: Presence of tumor cells within or surrounding a nerve.
  • Diagnostic criteria:
    • Tumor encircles at least one-third of the nerve's circumference.
    • Tumor cells are found within nerve sheath layers.
  • Clinical significance:
    • Indicator of tumor aggressiveness.
    • Independent risk factor for:
      • Cervical metastases
      • Local recurrence
      • Poor prognosis

Lymphovascular Invasion (LVI)

  • Definition: Tumor cells within blood vessels or lymphatics.
  • Significance:
    • Suggests higher likelihood of metastasis.
    • Associated with poorer outcomes.

Bone Invasion

  • Patterns:
    • Infiltrative
    • Erosive
    • Mixed
  • Clinical notes:
    • Tumors often invade bone at the point of contact.
    • Cortical erosion alone does not classify a tumor as T4.
    • Assessment of bone involvement is crucial for staging and treatment planning.

Metastases

  • Cervical node metastases:
    • Decrease prognosis by approximately 50%.
    • Commonly involve levels I and II.
  • Extranodal Extension (ENE):
    • Occurs when cancer breaches the lymph node capsule.
    • Strong adverse prognostic factor.
  • Distant metastases:
    • Rare in OCSCCs (2ā€“9% incidence).
    • Associated with ENE and bilateral neck disease.
    • Common sites include lungs, bones, and liver.

Examination, Investigation, Diagnosis, and Work-Up

Clinical Evaluation

  • History and examination of the oral cavity, oropharynx, and neck.
  • Signs and symptoms:
    • Non-healing ulcers
    • Persistent pain or discomfort
    • White or red patches (leukoplakia, erythroplakia)
    • Erosive or cavitated lesions
    • Difficulty in tongue movement
    • Numbness or sensory changes
    • Trismus (difficulty opening the mouth)
    • Ear pain (otalgia)
    • Difficulty swallowing (dysphagia)
  • Synchronous primary tumors:
    • Occur in 2.4ā€“4.5% of patients.
    • Thorough examination of the upper aerodigestive tract is essential.

Neck Examination

  • Palpation of all neck levels to assess for lymphadenopathy.
  • Clinical examination limitations:
    • Sensitivity of 74% for detecting lymphadenopathy.
    • Imaging is necessary for accurate assessment.
  • Impact on prognosis:
    • Presence of neck metastasis decreases survival rates significantly.

Biopsy

Primary Tumor Biopsy

  • Incisional biopsy is the gold standard.
  • Technique:
    • Avoid necrotic areas.
    • Obtain a narrow, deep sample.
  • Other methods:
    • Exfoliative cytology and brush biopsy are less sensitive and not routinely used.

Neck Lump Biopsy

  • Fine-needle aspiration cytology (FNAC):
    • First-line investigation for neck lymphadenopathy.
    • Sensitivity: 89ā€“98%.
    • Helps differentiate between various malignancies (e.g., lymphoma, thyroid cancer).

Imaging

Computed Tomography (CT)

  • Contrast-enhanced CT (CECT):
    • Commonly used for staging.
    • Advantages:
      • Rapid image acquisition.
      • Excellent for assessing bone involvement.
      • Useful for thoracic staging.

Magnetic Resonance Imaging (MRI)

  • Benefits:
    • Superior soft-tissue contrast.
    • Preferred for defining primary tumor extent.
    • Better for detecting perineural spread and bone marrow invasion.
  • Sensitivity and specificity:
    • 82% sensitivity and 66.7% specificity for detecting bone invasion in the mandible.

Positron Emission Tomographyā€“Computed Tomography (PET-CT)

  • Uses:
    • Detection of distant metastases or synchronous tumors.
    • Investigation of unknown primary tumors.
    • Post-treatment surveillance.
  • Not a first-line imaging modality for initial staging.

Plain Film and Panoramic Radiographs

  • Utility:
    • Evaluating dental health.
    • Planning prophylactic dental treatments.
    • Identifying infection or inflammation.
  • Limitations:
    • Less informative for soft-tissue assessment.

Ultrasound

  • Applications:
    • Guiding FNAC of suspicious lymph nodes.
  • Operator-dependent technique.
  • Effectiveness:
    • 85% sensitivity and 78.9% specificity for detecting cervical lymphadenopathy.
  • Limited role in assessing primary oral cavity tumors.

Sentinel Lymph Node Biopsy (SLNB)

  • Purpose:
    • Staging the neck in patients without clinical or radiological lymph node involvement (cN0).
  • Sentinel node:
    • The first lymph node to which cancer cells are likely to spread.
  • Procedure:
    • Identifies presence of metastasis in sentinel node(s).
    • Guides decision on further neck treatment (e.g., neck dissection).
  • Benefits:
    • Reduces overtreatment in patients without nodal metastasis.
    • May detect unexpected contralateral lymph node drainage.
  • Limitations:
    • False-negative rate of 14%.
    • Comparative survival data between SLNB and elective neck dissection is lacking.

Note: Regular surveillance and multidisciplinary management are crucial for optimal outcomes in patients with oral cavity cancer.

Surgical Management of Oral Cavity Cancer

Introduction

  • Surgery with or without adjuvant radiotherapy or chemoradiotherapy remains the mainstay of treatment.
  • Evolution towards function-sparing techniques and away from radical procedures.
  • Reconstruction of defects improves quality of life.
  • Influenced by:
    • Improved understanding of tumor biology.
    • More accurate staging investigations.
    • Advances in microvascular free tissue transfer.
  • Survival largely dictated by tumor biology (e.g., nodal metastases with extranodal extension [ENE]).

Key Principles

  1. Patient Selection
  2. Key Surgical Decisions
  3. Reconstruction
  4. Multidisciplinary Care

Patient Selection

  • Assess comorbidities, functional status, and social circumstances.
  • Early involvement of the multidisciplinary team (MDT):
    • Physicians
    • Anaesthetists
    • Physiotherapists
    • Dieticians
  • Aim to optimize performance status preoperatively.
  • Operability determined by tumor size and anatomical relationships.
    • T4b tumors (AJCC 8th edition) may be unresectable due to invasion of critical structures:
      • Skull base
      • Masticator space
      • Pterygoid plates
      • Internal carotid artery

Key Surgical Decisions

  1. Airway Management
  2. Access to the Tumor
  3. Tumor Resection
  4. Management of the Neck
  5. Reconstruction

Airway Management

  • Goal: Protect airway during perioperative period.
  • Options:
    • Immediate postoperative extubation:
      • For small, well-lateralized tumors without reconstruction.
    • Overnight intubation/delayed extubation:
      • For selected patients where tracheostomy is unlikely.
      • Allows for quick restoration of speech and swallowing.
    • Submental intubation
    • Tracheostomy:
      • Low threshold in:
        • Bilateral neck dissection
        • Large resections with reconstruction
        • Difficult airway
        • Segmental mandibular resection
        • Lateral floor of mouth resections
        • Previously irradiated patients
  • Decision Factors:
    • Joint decision between anaesthetist and surgeon.
    • Ability to re-establish airway quickly in emergencies.

Access Surgery

  • Goal: Achieve adequate circumferential margins during tumor removal.
  • Transoral approach sufficient for most tumors.
  • Access procedures needed for:
    • Large maxillary tumors
    • Posteriorly located tumors
    • Tongue base tumors
    • Patients with prior surgery/radiotherapy
  • Common Access Procedures:
    • Lip-split mandibulotomy (LSM):
      • Most common.
      • Provides access to posterior oral cavity, tongue base, oropharynx.
      • Involves osteotomy to swing mandible laterally.
      • Care to prevent tearing of lingual mucosa towards resection margin.
    • Mandibular lingual release
    • Visor flap
    • Weberā€“Fergusson approach:
      • Access to maxilla and periorbital area.

Tumor Resection

  • Standard: Resection with 1-cm clinical margin circumferentially, preserving vital structures.

Mandibular Resection

  • Critical Decisions when tumor is close to or invades bone.
  • Types of Resection:
    • Segmental Resection:
      • Removal of full height of mandible segment.
      • Results in loss of continuity of lower border.
    • Rim Resection (Marginal Mandibulectomy):
      • Partial thickness removal.
      • Continuity of lower border maintained.
      • Performed when tumor is close but not definitively invading bone.

Maxillary Resection

  • Considerations differ due to:
    • Thinner bone
    • Presence of sinuses
    • Tightly adherent palatal mucosa
    • Proximity to orbit and skull base
  • Small Tumors:
    • Managed by transoral partial maxillectomy.
  • Extensive Tumors:
    • Require wider access via Weberā€“Fergusson incision.
    • Invasion into pterygoid space or infratemporal fossa indicates poor prognosis.
  • Orbital Involvement:
    • May require orbital exenteration or combined neurosurgical resection.
  • Reconstruction Goals:
    • Provide oral seal.
    • Restore facial profile and tissue loss.
    • Facilitate dental rehabilitation.

Management of the Neck

  • Neck Dissection:
    • Elective or therapeutic.
  • Therapeutic Neck Dissection:
    • Indicated with clinical/radiographic evidence of cervical metastases.
  • Elective Neck Dissection:
    • For early-stage disease without evident metastases.
    • Improves overall and disease-specific survival compared to watchful waiting.
  • Sentinel Lymph Node Biopsy (SLNB):
    • Used to detect occult metastases.
    • Guides decision for neck dissection in small tumors.
  • Evolution of Neck Dissections:
    • Shift towards less radical, more selective procedures.
    • Selective Neck Dissection involving levels Iā€“III is standard for OCSCC.
  • Purposes of Neck Dissection:
    • Staging and prognosis.
    • Therapeutic removal of disease.
    • Informing need for adjuvant therapy.
    • Access to recipient vessels for microvascular reconstruction.

Reconstruction

  • Key Component post-tumor ablation.
  • Should not influence ablative procedure decisions.
  • Goals:
    • Preserve or restore speech, chewing, swallowing, and oral continence.
    • Facial aesthetics are important but secondary to function.
  • Principles:
    • Replace resected tissue with similar tissue.
    • Use simplest method meeting reconstruction aims.
    • Consider vascularized tissue in previously irradiated sites.
    • Have an alternative plan in case of primary reconstruction failure.
  • Reconstruction Ladder:
    • A useful algorithm guiding reconstruction options:
      • Healing by secondary intention
      • Primary closure
      • Skin grafting
      • Local flaps
      • Regional flaps
      • Microvascular free tissue transfer

Free Flaps

  • Definition: Vascularized tissue from a distant site, transplanted with microvascular anastomosis.
  • Tissue Types:
    • Skin
    • Fascia
    • Muscle
    • Tendon
    • Bone
  • Advantage: Can replace both bone and soft tissue in the oral cavity.

Soft-Tissue Reconstruction

  • Common Flaps:
    • Radial Forearm Free Flap (RFFF):
      • Thin, pliable, non-hairy.
      • Long vascular pedicle.
      • Ideal where minimal bulk is needed.
    • Anterolateral Thigh (ALT) Flap:
      • Provides greater bulk.
      • Suitable for tongue reconstruction.
      • Can include multiple skin paddles or muscle components.
  • Alternative Flaps:
    • Rectus abdominis
    • Latissimus dorsi
    • Medial sural artery perforator
    • Lateral arm flaps

Composite Reconstruction

  • Bone-Containing Flaps:
    • Fibula Free Flap:
      • Most commonly used globally.
      • Good for mandibular reconstruction.
    • Iliac Crest (DCIA) Flap
    • Scapula Flap
    • Composite RFFF
  • Chimeric Flaps:
    • Independently mobile osseous and soft-tissue components.
    • Example: Thoracodorsal system flaps.
    • Used for complex reconstructions.

Reconstruction by Anatomical Subsite

Soft-Tissue Reconstruction

  • Intraoral Sites:
    • Tongue
    • Floor of mouth
    • Buccal mucosa
    • Retromolar area
    • Soft palate
  • Flap Selection:
    • RFFF for areas needing minimal bulk.
    • ALT Flap for tongue and areas requiring bulkiness for function.

Mandible Reconstruction

  • Gold Standard: Reconstruction with composite free flaps.
  • Considerations:
    • Defect site, size, and complexity.
    • Patient comorbidities.
    • Surgeon expertise and preference.
  • Principles:
    • Anterior defects are more challenging.
    • Use flap curvature to mimic natural mandible shape.
    • Reduce span in edentulous patients to avoid prominent chin.
    • Be cautious of free bone as a potential infection source post-radiotherapy.

Maxillary Reconstruction

  • Aims:
    • Restore facial contours and aesthetics.
    • Separate sinonasal cavities from the mouth.
    • Restore soft palate competence.
    • Provide for dental replacement.
  • Classification System:
    • Brown and Shaw Classification:
      • Considers vertical (Classes Iā€“VI) and horizontal (aā€“c) defect extent.
  • Reconstruction Strategies:
    • Class I: Local flaps or RFFF to separate cavities.
    • Class II: Similar to Class I; composite flaps for anterior defects.
    • Classes III & IV: Composite free flaps to support orbit and facial skin.
  • Prosthetic Reconstruction:
    • Obturator denture is an alternative.
    • Free flap reconstruction offers better functional and aesthetic outcomes.

Zygomatic Implants and ZIP Flaps

  • Zygomatic Implants:
    • Support prosthetic rehabilitation post-maxillectomy.
    • Can be used with soft-tissue flaps.
  • Zygomatic Implant Perforator (ZIP) Flaps:
    • Implants perforate through soft-tissue free flap.
    • Placed immediately after tumor ablation.

Virtual Surgical Planning (VSP)

  • Increasing Use in oral cavity reconstruction.
  • Benefits:
    • Reduced operating time.
    • Greater accuracy.
    • Improved aesthetic and functional outcomes.
  • Process:
    • Preoperative CT scans and software create patient-specific surgical stents and cutting guides.
    • Virtual surgery performed by the surgeon.
    • Cutting guides assist in both resection and donor site harvesting.
    • Prefabricated reconstruction plates may be used.

Adjuvant Therapy for Oral Cavity Cancer

Indications for Adjuvant Therapy

  • Based on pathological features of the tumor.
  • Adverse Features prompting adjuvant therapy:
    • Extranodal extension (ENE)
    • Close/involved margins
    • Lymphovascular invasion (LVI)
    • Perineural invasion (PNI)
  • Criteria for Radiotherapy:
    • One major criterion:
      • ENE
      • Involved margin (<1 mm)
    • Two minor criteria:
      • Close margin (1ā€“4.9 mm)
      • Multiple involved nodes
      • Largest node >3 cm
      • LVI/PNI
      • T3 or T4 tumor stage

Adjuvant Chemoradiotherapy

  • Standard Treatment for high-risk patients.
  • Landmark Trials:
    • RTOG 9501 and EORTC 22931
  • Findings:
    • Adding high-dose cisplatin to postoperative radiotherapy improves:
      • Locoregional control
      • Progression-free survival
  • High-Risk Factors:
    • Positive surgical margins
    • Extracapsular extension (ECE) (now termed ENE)
  • Outcome:
    • Strong evidence supporting concurrent cisplatin-based chemoradiotherapy in high-risk patients.

Immunotherapy

  • Concept: Tumors can evade immune system via immune checkpoints.
  • Target Pathway:
    • Programmed death receptor-1 (PD-1) and its ligand PD-L1.
  • Mechanism:
    • Tumor uses PD-1/PD-L1 interaction to evade immune response.
  • Clinical Evidence:
    • Phase III trials show PD-1 inhibitors prolong survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
  • Implications:
    • Represents a paradigm shift in treatment.
    • Potential for further research into checkpoint inhibition in HNSCC management.

Management of Recurrent and/or Metastatic Disease

  • Salvage Surgery and/or Radiotherapy:
    • Offered to patients with:
      • Low disease burden
      • Oligometastatic deposits
      • Satisfactory performance status
  • Systemic Treatment:
    • For patients not amenable to surgery/radiotherapy.
  • Treatment Options:
    • Depend on previous platinum-containing chemotherapy exposure.
    • Include:
      • Immunotherapy
      • Palliative chemotherapy regimens
  • Prognosis:
    • Remains poor for these patients.

Note: Multidisciplinary care and regular follow-up are essential components in the management of oral cavity cancer to ensure optimal outcomes.