วันอาทิตย์ที่ 5 เมษายน พ.ศ. 2569

Head and Neck Cancer

Head and Neck Cancer

Epidemiology & Risk Factors

1. Epidemiology

  • พบทั่วโลก ~ 900,000 cases/ปี, เสียชีวิต ~400,000/ปี
  • เพศชายมากกว่าหญิง (≈ 2–4:1)
  • High-incidence regions:
    • South Asia → oral cavity cancer
    • Southern China → nasopharyngeal carcinoma
    • Europe → laryngeal/pharyngeal cancer

2. Core Pathogenesis

  • Chronic exposure → upper aerodigestive tract mucosa injury
  • → dysplasia → premalignant lesion → carcinoma

3. Major Risk Factors (High-yield)

3.1 Tobacco

  • Strongest risk factor
  • Risk ↑ 5–25 เท่า (dose-dependent)
  • สูบ >1 pack/day → risk ↑ ~13 เท่า
  • Passive smoking → ↑ risk (especially female, tongue cancer)
  • Smokeless tobacco → oral cavity / pharynx cancer

👉 Smoking cessation → risk ↓ และกลับใกล้ baseline ใน ~20 ปี

3.2 Alcohol

  • Independent risk (dose-dependent)
  • 50 g/day → risk ↑ ~5–6 เท่า
  • Synergistic with smoking (multiplicative effect)

3.3 Viral infection

  • HPV (type 16)
    • Oropharynx (tonsil, base of tongue)
    • Younger, non-smoker
  • EBV
    • Nasopharyngeal carcinoma (especially Asia)
  • Others (weaker/association):
    • HCV, HIV → ↑ risk
    • HSV → unclear clinical significance

3.4 Betel nut (หมาก)

  • Independent risk (Asia)
  • Synergy กับ tobacco + alcohol

3.5 Immunodeficiency

  • HIV → ↑ SCC head & neck ~2–3 เท่า
  • Post-transplant → ↑ malignancy

3.6 Occupational / Environmental

  • Asbestos, formaldehyde, PAHs, wood dust
  • Textile, construction, metal work
  • Agent Orange → oropharynx / larynx / thyroid

3.7 Radiation

  • Prior radiation → ↑ thyroid, salivary gland, SCC
  • latency ยาว

3.8 Diet

  • Protective: fruits, vegetables
  • Risk ↑: preserved meat (nitrites) → nasopharyngeal CA

3.9 Genetic predisposition

  • DNA repair defects
  • Fanconi anemia → early-onset H&N cancer

3.10 Others

  • Poor oral hygiene / periodontal disease
  • Chronic inflammatory tongue disease
  • Alcohol-based mouthwash (long-term heavy use, weak association)

4. Clinical Insight (High-yield for practice)

Pattern recognition

  • Smoker + alcohol → classic SCC
  • Young, non-smoker, tonsil/base tongue → think HPV
  • Asian patient + neck mass → rule out EBV NPC
  • Betel nut → oral cavity cancer

Key Takeaways (Exam / Practice pearls)

  • Smoking + alcohol = most important modifiable risks
  • HPV-related cancer → prognosis better than non-HPV
  • Geographic variation สำคัญต่อ differential diagnosis
  • Chronic inflammation + carcinogen exposure → key mechanism

Pathology, Diagnosis, Prognostic factors

1. Overview

  • Head & neck region: oral cavity, pharynx, larynx, sinonasal, salivary gland ฯลฯ
  • Most common malignancy = Squamous cell carcinoma (SCC)

2. Diagnosis & Specimen Handling

2.1 Tissue diagnosis

  • Biopsy (gold standard)
    • incisional/excisional → ให้ข้อมูล invasion + margin + prognostic features
  • FNA
    • ใช้ใน lymph node, thyroid, salivary gland
    • เหมาะสำหรับ staging มากกว่า mucosal lesion

❗ Frozen section:

  • ไม่ควรใช้เป็น diagnostic tool หลัก
  • ใช้ intra-op เพื่อประเมิน margin/adequacy เท่านั้น

2.2 Surgical margin (สำคัญมาก)

  • Goal: negative margin
  • Definition:
    • Clear margin ≥5 mm
    • Close margin <2–5 mm
  • Positive margin → ต้อง re-excision หรือ adjuvant CRT

👉 “Specimen margin” ดีกว่า “tumor bed margin”

3. Precursor lesions (High-yield)

3.1 Clinical lesions

  • Leukoplakia (white)
  • Erythroplakia (red → risk สูงกว่า)
  • Mixed lesion

👉 ต้อง biopsy ทุกกรณีที่ suspicious

3.2 Histologic precursor

  • Squamous dysplasia = premalignant lesion หลัก
    • WHO: mild / moderate / severe
    • หรือ low-grade vs high-grade
  • Risk of progression:
    • No dysplasia → ~2%
    • Severe dysplasia → ~30%

❗ Key point:

  • ไม่ได้ progression แบบ linear เสมอ
  • cancer อาจเกิดโดยไม่มี dysplasia

3.3 Special precursor

  • Proliferative verrucous leukoplakia (PVL)
    • high risk malignant transformation
    • มักในหญิงสูงอายุ
    • ไม่สัมพันธ์ smoking

4. Pathogenesis pathways (สำคัญมาก)

3 major pathways:

1.       Tobacco + alcohol → TP53 mutation

2.       HPV (esp. type 16) → oropharynx

3.       EBV → nasopharynx

5. Pathologic features of SCC

  • Invasion = breach basement membrane
  • Pattern:
    • nests / cords / single cells
  • Keratinization → keratin pearl
  • Intercellular bridges → squamous differentiation

👉 Poorly differentiated → ใช้ IHC:

  • p63 / p40
  • CK5/6

6. Prognostic factors (Clinical + Pathology)

6.1 Most important

  • Stage (TNM) → determinant หลัก

6.2 Pathologic prognostic factors

Tumor factors

  • Depth of invasion (DOI) → nodal risk
  • Pattern of invasion (single cells = worse)
  • Histologic grade → limited value

Spread-related

  • Lymphovascular invasion
  • Perineural invasion

Node-related

  • Extracapsular extension (ENE)
    • strong negative prognostic factor
    • → indication for adjuvant CRT

Margin

  • Positive / close margin → ↑ recurrence

7. HPV-associated SCC (high-yield clinical)

Features

  • Younger, non-smoker
  • Oropharynx (tonsil/base tongue)
  • Early nodal metastasis
  • Better prognosis

Morphology

  • Non-keratinizing
  • No dysplasia overlying

Testing

  • p16 IHC (screening)
  • confirm with mRNA ISH

8. Important variants of SCC

Verrucous carcinoma

  • Low-grade, slow growth
  • ไม่ metastasis
  • treatment = surgery

Basaloid SCC

  • aggressive
  • tobacco-related
  • high mortality

Spindle cell SCC

  • mimic sarcoma
  • high recurrence
  • ต้องใช้ IHC ช่วย

9. Biomarkers (clinical use)

HPV testing

  • p16 IHC → screening
  • mRNA ISH → gold standard

PD-L1

  • ใช้กำหนด immunotherapy (pembrolizumab)
  • ใช้ CPS score

10. Clinical Pearls (ใช้จริง)

  • Neck mass → คิดถึง metastatic SCC จนกว่าจะพิสูจน์ว่าไม่ใช่
  • Oropharyngeal cancer → ต้อง check HPV
  • Margin + ENE → กำหนด adjuvant treatment
  • Dysplasia → ต้อง follow-up ใกล้ชิด

🔑 Key Takeaways

  • SCC = most common H&N cancer
  • Diagnosis = biopsy (FNA สำหรับ node/staging)
  • Prognosis = stage + ENE + margin + DOI
  • HPV-positive = better prognosis
  • Dysplasia = premalignant แต่ predict ยาก

Initial Evaluation, Diagnosis & Staging

1. Overview

  • Tumor sites: oral cavity, pharynx, larynx, sinonasal, salivary gland
  • Most common histology = SCC (~90–95%)

2. When to suspect (Red flags ⚠️)

👉 Adult with unexplained symptoms ต้องคิดถึง cancer เสมอ

Key symptoms

  • Neck mass (สำคัญที่สุด)
  • Referred otalgia (CN V, VII, IX, X)
  • Hoarseness
  • Dysphagia / odynophagia
  • Epistaxis / nasal obstruction
  • Oral ulcer ไม่หาย
  • Hemoptysis / blood-stained saliva
  • Unilateral tonsil enlargement

👉 Neck mass in adult = malignancy until proven otherwise

3. Clinical presentation by site (high-yield)

Oral cavity

  • Non-healing ulcer, pain, bleeding
  • Loose teeth, dysarthria → advanced
  • Cervical node ~2/3 cases

Oropharynx

  • Dysphagia, odynophagia, otalgia
  • HPV+ → painless cystic neck mass

Nasopharynx

  • Neck mass (~90%)
  • Hearing loss (serous otitis media)
  • CN palsy (advanced)

Larynx

  • Early: hoarseness
  • Late: stridor, dyspnea

Hypopharynx

  • Late presentation
  • Dysphagia + weight loss

Sinonasal

  • Nasal obstruction + epistaxis
  • Late: facial pain, proptosis

Salivary gland

  • Mass
  • Facial nerve weakness → malignancy

4. Initial evaluation (clinical workflow)

Step 1: Referral

  • ENT / head & neck specialist

Step 2: Physical exam

  • Inspect + palpate oral cavity
  • Flexible laryngoscopy (สำคัญมาก)
  • Examine neck nodes + salivary gland

Step 3: Imaging

First-line

  • CT neck + contrast
  • CT chest

MRI → better for:

  • Soft tissue / tongue
  • Skull base / perineural spread

PET/CT → ใช้เมื่อ:

  • Unknown primary
  • Bulky disease
  • Suspect metastasis / second primary

5. Tissue diagnosis

5.1 Preferred approach

  • FNA (neck node) → first-line
    • sensitivity 89–98%
  • Biopsy primary lesion (ถ้า accessible)

5.2 Clinical scenarios

Situation

Approach

Neck mass

FNA

Known primary

biopsy node เพื่อ staging

No node

biopsy primary

Suspect metastasis

biopsy metastatic site

6. Imaging interpretation (key points)

Lymph node malignancy criteria

  • 10–11 mm
  • central necrosis

❗ limitation:

  • miss microscopic metastasis
  • nodes <10 mm อาจ positive ได้

PET/CT advantages

  • Detect:
    • unknown primary (~97% sensitivity)
    • distant metastasis
    • second primary

❗ ต้อง biopsy confirm (false positive สูง)

7. Histology (high-yield)

Common types

  • SCC (90–95%)
  • Others:
    • Nasopharyngeal carcinoma
    • Melanoma
    • Salivary gland tumor

SCC characteristics

  • Develop from:
    • leukoplakia / erythroplakia / dysplasia

HPV testing

  • ใช้ใน oropharyngeal SCC เท่านั้น
  • p16 IHC (≥70% positive)
  • confirm with ISH/PCR หากไม่ชัด

8. Staging

Basis

  • Clinical exam + imaging + pathology

System

  • TNM (AJCC 8th edition)

Key concepts

T (tumor)

  • Size + local invasion
  • site-specific

N (node)

  • number + size + ENE

M (metastasis)

  • lung, liver, bone

9. Neck staging (important)

Methods

  • FNA (standard)
  • SLNB (early oral cavity)
  • Elective neck dissection

👉 SLNB:

  • less morbidity
  • high sensitivity

10. Clinical Pearls (ใช้จริง)

  • Neck mass → biopsy first (FNA)
  • HPV+ cancer → มัก present ด้วย node
  • Imaging ควรทำก่อน biopsy (PET distortion)
  • PET false positive สูง → ต้อง confirm
  • Small node ≠ benign

Key Takeaways

  • Red flag symptoms ต้องคิดถึง cancer เสมอ
  • FNA = first-line diagnostic tool
  • CT neck + chest = initial imaging
  • PET/CT → unknown primary / staging advanced
  • HPV testing → only oropharyngeal SCC
  • TNM staging → guide treatment

Treatment & Management

1. Core principle

  • Multidisciplinary care = standard
    • ENT surgeon + radiation oncologist + medical oncologist + rehab team
  • ควรรักษาใน high-volume center → outcome ดีกว่า

2. Treatment overview (ตาม stage)

🔹 2.1 Early stage (Stage I–II)

Options (curative intent):

  • Surgery หรือ
  • Definitive radiation therapy (RT)

👉 Outcome:

  • 5-year survival ~70–90%

Site-specific note

  • Oral cavity → surgery preferred
  • RT = alternative ถ้า surgery ไม่เหมาะ

Surgical techniques

  • Wide excision
  • Transoral approaches:
    • TOLM (laser)
    • TORS (robotic)

👉 ลด morbidity / better function

RT techniques

  • IMRT / IGRT → ลด toxicity

3. Adjuvant therapy (หลัง surgery)

Indications (high-yield ⚠️)

  • Positive / close margin
  • Perineural invasion (PNI)
  • Lymphovascular invasion (LVI)
  • Extracapsular extension (ENE)
  • Multiple nodes

👉 ให้:

  • RT หรือ
  • Concurrent chemoradiotherapy (CRT)

4. Locoregionally advanced (Stage III–IV)

👉 ต้องใช้ combined modality

Options

1.       Surgery → + adjuvant RT/CRT

2.       Concurrent chemoradiotherapy (organ preservation)

3.       Induction chemotherapy → CRT

4.       Sequential therapy

Site-based strategy

Oral cavity

  • Surgery = first-line
  • adjuvant RT/CRT almost always

Oropharynx / Larynx / Hypopharynx

  • Organ preservation approach preferred
    • CRT
    • TORS/TOLM

👉 หลีกเลี่ยง radical surgery ถ้าเป็นไปได้

Special populations

  • Elderly / poor performance:
    • RT alone (avoid chemo)

5. Immunotherapy (modern concept)

Indication

  • PD-L1 CPS ≥1
  • Neoadjuvant / adjuvant setting
  • Recurrent/metastatic

👉 Drugs:

  • Pembrolizumab
  • Nivolumab

6. Management of neck nodes

Key principle

  • Node involvement = worse prognosis

Strategy

  • Clinically positive node:
    • RT/CRT ± surgery
  • Post-RT evaluation:
    • Complete response → observe
    • Residual → salvage surgery

Elective treatment

  • ถ้า risk occult node >15–20% → treat neck

7. Reconstruction & rehabilitation

Goals

  • Speech
  • Swallowing
  • Cosmesis

Techniques

  • Local flap
  • Free flap (fibula, radial forearm)
  • Prosthesis (obturator)

Rehab

  • Speech therapy
  • Swallow rehab

👉 สำคัญมากต่อ QoL

8. Complications (high-yield)

Acute

  • Mucositis
  • Dermatitis
  • Dysphagia
  • Weight loss

Late

  • Xerostomia
  • Osteoradionecrosis
  • Aspiration
  • Fibrosis

9. Post-treatment surveillance

Timeline

  • First 2–4 ปี → recurrence สูงสุด (80–90%)

Follow-up

  • Clinical exam
  • Imaging:
    • CT/MRI (4–6 wk)
    • PET/CT (~12 wk)

👉 อย่าทำ PET เร็วเกิน → false positive

Long-term

  • lifelong follow-up
  • monitor:
    • recurrence
    • second primary

10. Recurrence / Metastatic disease

Locoregional recurrence

  • Salvage surgery ± RT/chemo

Metastatic disease

  • Palliative:
    • chemo
    • immunotherapy
    • RT (symptom control)

11. Special diseases

HPV-related oropharynx

  • Better prognosis
  • Same treatment (outside trial)

Nasopharyngeal carcinoma

  • RT + chemo = mainstay
  • Surgery rarely used

Salivary gland cancer

  • Surgery ± RT

🔑 Key Takeaways

  • Early stage → surgery หรือ RT
  • Advanced → multimodality (CRT ± surgery)
  • Oral cavity → surgery first
  • Oropharynx/larynx → organ preservation
  • ENE / margin / nodes → guide adjuvant
  • Neck node management สำคัญมาก
  • Follow-up ต้องยาวและเข้ม
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