What are the diagnostic and treatment approaches for a patient presenting with symptoms suggestive of oral cancer, such as a non-healing sore in the mouth or lip and difficulty swallowing?

Diagnostic Approach to Oral Cancer

The diagnosis of oral cancer requires a thorough clinical examination followed by biopsy of suspicious lesions, with pathological confirmation being mandatory for definitive diagnosis. 1

Clinical Presentation and Warning Signs

• Symptoms that should prompt clinical examination for oral cancer include:
  • Non-healing ulcers or sores in the mouth or lip 1
  • Red or white patches in the mouth (erythroplakia or leukoplakia) 1
  • Difficulty swallowing (dysphagia) 1
  • Chronic pain in the throat or mouth 1
  • Persistent sore throat 1
  • Lumps, bumps, or masses in the oral cavity or neck 1
  • Foul oral cavity odor independent of hygiene practices 1
  • Difficulty moving the jaw or tongue 1
  • Loose teeth or ill-fitting dentures 1
  • Unexplained weight loss and/or fatigue 1

Diagnostic Workup

• Clinical evaluation must include: 1

  • Complete physical examination including neck palpation
  • Flexible head and neck fibreoptic endoscopy
  • Assessment of performance status and nutritional status
  • Dental examination
  • Speech and swallowing function evaluation

• Pathological confirmation is mandatory and considered the gold standard for diagnosis 1, 2

  • Examination and biopsy can be performed transorally under local anesthesia 1
  • For pharyngolaryngeal tumors, endoscopic route under general anesthesia is often preferred 1
  • Any suspicious lesion that does not subside within two weeks from detection and removal of local causes of irritation must be biopsied 2

• Laboratory tests that should be routinely performed: 1

  • Complete blood count
  • Liver enzymes
  • Serum creatinine
  • Albumin
  • Coagulation parameters
  • Thyroid-stimulating hormone (TSH)

Imaging Studies

• Contrast-enhanced (CE) computed tomography (CT) scan and/or magnetic resonance imaging (MRI) are mandatory to: 1

  • Assess the primary tumor and regional lymph nodes
  • Evaluate cartilage invasion for laryngeal or hypopharyngeal cancer
  • Both imaging techniques are complementary and should be discussed with a radiologist specialized in head and neck cancer

• Chest imaging is important to: 1

  • Assess for distant metastases in high-risk tumors (particularly those with neck adenopathies)
  • Screen for a second lung primary in heavy smokers
  • At minimum, a chest CT should be performed

• FDG-PET (positron emission tomography) is recommended for: 1

  • Work-up of carcinoma of unknown primary to direct specific mucosal biopsy
  • Evaluating neck response to radiotherapy or chemoradiotherapy 10-12 weeks after treatment
  • Cases of suspected recurrence

Pathological Assessment

• Squamous cell carcinoma of the head and neck (SCCHN) should be classified according to the WHO classification 1

• For oropharyngeal tumors: 1

  • HPV evaluation using p16 immunohistochemistry (IHC) should be performed on all newly diagnosed oropharyngeal SCC
  • p16 IHC is a reliable surrogate marker for HPV positivity in the oropharynx (10-15% false-positive results)

• For neck metastases of unknown origin: 1

  • p16 status should be assessed
  • If positive, another specific HPV test (DNA, RNA or in situ hybridization) should be performed to confirm HPV status
  • Epstein-Barr virus (EBV) status should be determined by EBER using ISH to exclude nasopharyngeal cancer

• Pathological assessment of surgical specimens should include: 1

  • Tumor size
  • Growth pattern
  • Depth of invasion (for oral cavity cancer)
  • Total number of lymph nodes removed
  • Number of invaded lymph nodes and their location
  • Presence of extracapsular nodal extension
  • Peri-neural and lymphatic infiltration
  • Surgical margins

Adjunctive Diagnostic Tools

• Toluidine blue vital staining may be used as an adjunct to soft tissue examination to highlight invisible, asymptomatic lesions 2, 3

• Autofluorescence imaging can help clinicians in the diagnostic pathway 2

• Exfoliative cytology can detect early oral cancer and may be useful in population-based screening programs 3

• Oral CDx brush biopsy technique has been proposed as an accurate method of detecting oral precancerous and cancerous lesions 3

Clinical Pitfalls and Caveats

• Early oral cancer can appear as an innocuous red or white change, an ulcer, or a lump, mimicking many benign lesions 4

• When discomfort is minimal, professional consultation is often delayed, increasing the chance for local spread and regional metastases 4, 5

• Delays in diagnosis can be attributed to patients (40.6%), doctors (24.9%), or both (10.8%) 5

• Only 47.5% of patients report because of the initial symptom noticed, with nearly half reporting after 3-6 months of observing symptoms 5

• Early detection followed by appropriate treatment can increase cure rates to about 80% (compared to overall survival rates of approximately 50%) 4, 6

• A significant percentage of oral cancers are reported at an advanced stage (73.5% in stages III and IV combined) 5