What are the diagnostic and treatment approaches for different types of head and neck cancer?

Head and Neck Cancer: Diagnosis and Treatment by Subtype

For head and neck cancers, diagnosis requires WHO-classified surgical biopsy with staging via physical examination, endoscopy, CT or MRI imaging, and treatment is determined by anatomic site and stage—with early disease (Stage I-II) managed by single-modality therapy (surgery or radiotherapy) and locally advanced disease (Stage III-IV) requiring surgery plus postoperative radiotherapy, or postoperative chemoradiotherapy with platinum for high-risk features. 1

Epidemiology and Histologic Distribution

• Squamous cell carcinoma accounts for more than 90% of all head and neck malignancies, making it the dominant histology requiring standardized management approaches 1, 2
• The crude incidence in Europe is 36/100,000/year in males and 7/100,000/year in females, with mortality rates of 18 and 3/100,000/year respectively 1
• Five-year survival is 42% overall, with better outcomes in women (51%) versus men (39%), and younger patients (54% for ages 15-45) versus older patients (35% for ≥75 years) 1

Diagnostic Approach (Universal Across Subsites)

Tissue Diagnosis

• Pathological diagnosis must be obtained from surgical biopsy and classified according to WHO criteria 1

Staging Workup

• Physical examination, head and neck endoscopy, and chest X-ray are mandatory baseline studies 1
• MRI is the preferred imaging modality for all tumor subsites EXCEPT laryngeal and hypopharyngeal cancers, where CT is acceptable 1
• Thoracic CT scan should be performed to exclude metastatic disease and second lung primaries 1
• PET-CT has lower specificity than sensitivity and is more useful for detecting distant metastases or synchronous tumors than for neck node staging 1
• All tumors must be staged using the TNM system with T4 tumors subdivided into T4a (moderately advanced/resectable) and T4b (very advanced/unresectable) 1

Treatment by Stage (Applies to Most Subsites)

Early Stage Disease (Stage I-II)

• Either conservative surgery OR radiotherapy (external beam or brachytherapy) provides equivalent locoregional control, though this recommendation is based on retrospective data without randomized trial support 1
• Modern radiotherapy should utilize 3D conformal radiation therapy or intensity-modulated radiation therapy (IMRT) 1

Locally Advanced Resectable Disease (Stage III-IVa)

• Standard treatment is surgery with reconstruction followed by postoperative radiotherapy 1
• For patients with high-risk pathologic features (extracapsular nodal extension and/or R1 resection), postoperative chemoradiotherapy with single-agent platinum is mandatory 1
• When anticipated functional outcome is poor or surgery would be mutilating, concurrent chemoradiotherapy alone should be considered as an organ preservation strategy 1

Organ Preservation Strategies (Larynx and Hypopharynx)

• Neoadjuvant chemotherapy followed by radiotherapy allows organ preservation in advanced larynx and hypopharynx cancer requiring total laryngectomy, though this does NOT improve disease-free or overall survival 1
• Concurrent chemoradiotherapy achieves higher larynx preservation rates than sequential approaches 1
• Altered fractionation radiotherapy (hyperfractionation or accelerated fractionation) with or without concurrent chemotherapy represents an alternative organ preservation approach 1

Induction Chemotherapy

• Cisplatin/5-fluorouracil/docetaxel followed by radiotherapy or chemoradiotherapy produces higher response rates, longer disease-free progression, and longer overall survival compared to cisplatin/5-fluorouracil regimens 1
• Neoadjuvant therapy is NOT considered standard treatment in resectable disease 1

Site-Specific Considerations

Laryngeal Cancer

• Represents 60-65% glottic, 30-35% supraglottic, and 5% subglottic distribution 2
• Squamous cell carcinoma accounts for approximately 95% of primary laryngeal malignancies 2
• Five-year relative survival is approximately 61%, better than other head and neck sites 2

Oropharyngeal Cancer

• Includes base of tongue, tonsil, posterior pharyngeal wall, and soft palate 2
• Strongly associated with human papillomavirus (HPV), particularly tonsil and base of tongue tumors 2
• HPV-positive patients demonstrate better overall prognosis and treatment response 3

Oral Cavity Cancer

• Common sites include buccal mucosa, floor of mouth, anterior tongue, alveolar ridge, retromolar trigone, and hard palate 2

Hypopharyngeal Cancer

• Generally presents at advanced stages with poor prognosis due to late presentation and rich lymphatic drainage 2

Nasopharyngeal Cancer

• Worldwide incidence 0.5-1.0/100,000/year, higher in Southeast Asia 2
• Strongly associated with Epstein-Barr virus (EBV) infection 2
• Relatively high rate of distant metastases compared to other head and neck sites 2

Salivary Gland Cancers

• Less common than squamous cell carcinomas, with adenoid cystic carcinoma being one of the more frequent salivary malignancies 2

Recurrent and Metastatic Disease

Locoregional Recurrence

• In selected cases of localized recurrence, surgery (if operable) or re-irradiation should be considered 1

Metastatic Disease

• For most patients with metastatic disease, palliative chemotherapy is the standard option 1
• Weekly methotrexate may be considered as accepted treatment 1
• Combination chemotherapy (cisplatin, 5-fluorouracil, or taxanes) produces higher response rates 1

Immunotherapy Options

• Pembrolizumab is FDA-approved in combination with platinum and 5-FU for first-line treatment of metastatic or unresectable recurrent HNSCC 4
• Pembrolizumab monotherapy is approved for first-line treatment when tumors express PD-L1 (CPS ≥1) 4
• Pembrolizumab monotherapy is approved for recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy 4

Essential Supportive Care Measures

• A multidisciplinary treatment schedule must be established in all cases 1
• Patient nutritional status must be corrected and maintained throughout treatment 1
• Dental rehabilitation is mandatory before initiating radiotherapy 1

Critical Pitfalls to Avoid

• Do not rely on PET-CT alone for neck node staging due to lower specificity 1
• Do not use induction chemotherapy as standard treatment in resectable disease outside of organ preservation protocols 1
• Do not omit postoperative chemoradiotherapy in patients with extracapsular extension or positive margins, as this significantly impacts survival 1
• Paranasal sinus and nasopharynx cancers require different management protocols and are typically excluded from standard HNSCC treatment algorithms 1