What is the treatment for head and neck cancer?

Treatment of Head and Neck Cancer

For early-stage disease (stage I-II), single-modality treatment with either surgery or radiotherapy achieves equivalent survival outcomes of 70-90% at 5 years, with choice based on functional preservation and institutional expertise. 1, 2 For locoregionally advanced disease (stage III-IVb), concurrent cisplatin-based chemoradiotherapy is the standard of care, achieving 5-year survival rates of 25-60% for HPV-negative disease and over 80% for HPV-associated oropharyngeal cancer. 1, 2

Initial Workup and Staging

Before treatment planning, complete the following assessment:

• Complete head and neck examination with mirror and fiberoptic endoscopy to visualize the primary tumor and assess extent 1
• Biopsy of the primary site or fine-needle aspiration of neck nodes for pathologic diagnosis 1
• HPV testing is mandatory for all oropharyngeal cancers, as HPV-positive tumors have dramatically better prognosis and may influence treatment intensity 1, 2
• Contrast-enhanced CT or MRI of the primary site and neck to define tumor extent, depth of invasion, bone involvement, and nodal disease 1, 3
• FDG-PET/CT for stage III-IV disease to detect distant metastases and guide treatment planning 1, 3
• Dental evaluation with panorex imaging before radiotherapy to prevent osteoradionecrosis 1
• Nutrition, speech, and swallowing evaluation to establish baseline function 1

Treatment Algorithm by Stage

Early-Stage Disease (Stage I-II)

Surgery or radiotherapy alone are equivalent options with 5-year survival of 70-90% 1, 2:

• Surgery: Excision of primary with neck dissection guided by tumor thickness and depth of invasion 1
• Radiotherapy: 66-70 Gy in conventional fractionation achieves 80-90% local control for T1-T2 tumors 1
• For glottic T2N0 larynx cancer specifically, radiotherapy is preferred to preserve voice quality 1
• Postoperative radiotherapy is optional for early-stage disease without adverse features 1

Locoregionally Advanced Resectable Disease (Stage III-IVa)

The standard approach is surgery followed by risk-adapted adjuvant therapy 1, 4:

Surgical Approach

• Excision of primary tumor with bilateral neck dissection for most oropharyngeal and oral cavity cancers 1
• Margins must be assessed intraoperatively; margins <5 mm are considered inadequate 4

Risk-Stratified Adjuvant Therapy

For high-risk pathologic features (extracapsular extension and/or positive margins <5 mm):

• Concurrent chemoradiotherapy with cisplatin 100 mg/m² every 3 weeks for 3 cycles is the Category 1 standard of care 1, 4
• This regimen increases both disease-free and overall survival compared to radiotherapy alone 1, 4
• Alternative: cisplatin 50 mg weekly has also shown survival benefit 4

For intermediate-risk features (multiple positive nodes, perineural invasion, lymphovascular invasion without extracapsular extension):

• Postoperative radiotherapy alone (60-66 Gy to tumor bed, 54-60 Gy to neck) 1

For cisplatin-ineligible patients with high-risk features:

• Consider docetaxel 15 mg/m² weekly plus cetuximab (400 mg/m² loading, then 250 mg/m² weekly) with radiotherapy 4

Organ Preservation Strategy (Alternative to Surgery)

For patients wishing to avoid total laryngectomy or for unresectable disease:

• Concurrent chemoradiotherapy is the preferred definitive treatment 1
• Standard regimen: cisplatin 100 mg/m² every 3 weeks with radiotherapy to 70 Gy (2.0 Gy/fraction) to gross disease 1
• IMRT is preferred for oropharyngeal cancers to minimize dose to critical structures 1
• Concurrent chemoradiotherapy achieves higher larynx preservation rates than induction chemotherapy followed by radiotherapy 1

Induction chemotherapy (TPF: docetaxel/cisplatin/5-FU) followed by chemoradiotherapy:

• Leads to higher response rates and longer disease-free survival compared to cisplatin/5-FU alone 1
• However, this remains a Category 3 recommendation due to lack of consensus and increased toxicity 1
• Not considered standard for resectable disease 1

Unresectable Disease (T4b, Fixed Nodes)

Definitive concurrent chemoradiotherapy is the only curative-intent option 1:

• Cisplatin-based chemoradiotherapy is superior to radiotherapy alone for response rate, disease-free survival, and overall survival 1
• For poor performance status patients, radiotherapy alone should be considered 1
• Altered fractionation schedules (hyperfractionation, accelerated fractionation) may improve outcomes but increase toxicity 1

Post-Treatment Surveillance

FDG-PET/CT at 10-12 weeks post-chemoradiotherapy is critical to evaluate neck response and determine need for salvage neck dissection 3:

• Residual PET-positive disease requires salvage surgery if technically feasible 3
• Clinical examination with CT or MRI should be performed regularly, as 40% of patients develop recurrence, mostly within the first 2 years 1, 3

Recurrent and Metastatic Disease

For fit patients (performance status 0-1) with recurrent/metastatic disease:

• First-line: Pembrolizumab (anti-PD-1 immunotherapy) alone or combined with platinum-doublet chemotherapy achieves median survival of 12-15 months 2
• Alternative: Cetuximab plus cisplatin or carboplatin plus 5-FU achieves median survival of 10.1 months versus 7.4 months with platinum/5-FU alone 1, 5, 3

For poor performance status or chemotherapy-intolerant patients:

• Weekly methotrexate monotherapy is the accepted standard with median survival of approximately 6 months 1, 5, 3
• Combination chemotherapy produces higher response rates but no survival benefit over single-agent therapy 1

For isolated locoregional recurrence:

• Salvage surgery is preferred if technically feasible and offers the only chance for cure 1
• Re-irradiation may be considered in highly selected cases 1

Critical Pitfalls to Avoid

• Do not omit HPV testing in oropharyngeal cancers—this fundamentally changes prognosis and may influence treatment de-intensification strategies 1, 2
• Do not use adjuvant chemotherapy alone after surgery; it provides no benefit 1
• Do not use induction chemotherapy as standard for resectable disease outside clinical trials 1
• Extracapsular extension is an absolute indication for chemoradiotherapy, not radiotherapy alone 4
• Margins <5 mm warrant chemoradiotherapy when combined with other risk factors 4
• Concurrent chemoradiotherapy carries substantial toxicity (grade 3-4 mucositis, dysphagia, neutropenia) and should only be administered by experienced multidisciplinary teams 4