H&N CA: US ˜50K cases/y, 11K D/y. >90% = H&N squamous cell ca (SCCHN). M:F 3:1

RF: Tobacco, EtOH, HPV, EBV betel quid

Genetic syndromes: Overall, rare; Fanconi most common. Others: Lynch-2, Bloom, Li-Fraumeni, Xeroderma Pigmentosa

Special populations: Nasopharyngeal endemic in southern China and Hong Kong

Risk of 2nd 1° CA: ˜3%/y for aerodigestive tracts due to “field cancerization” by tobacco/EtOH (not HPV); → consider selective use of “triple endoscopy” = EGD, bronchoscopy, laryngoscopy

Oral cavity: Buccal mucosa, alveolar ridges, floor of mouth, hard palate, tongue (ant 2/3)

Oropharynx: Tongue (base), tonsils, soft palate, post pharyngeal wall to level of hyoid

Nasopharynx: Superior to soft palate

Hypopharynx: Hyoid bone to cricoid cartilage

Larynx: Divided into supraglottic, glottic; subglottic (rare)

p16 inactivation: Frequent alteration in SCCHN

EGFR: Alterations in >90% of all SCCHN; overexpression correlates w/poorer prognosis (JNCI 1998;90:824)

CCND1 overexpression affects: ↑ cell cycle progression

HPV: E6, E7 viral protein → inhibit p53, Rb, other tumor suppressors

EBV: → LMP1, other viral proteins → ↑ cell replication; a/w nasopharyngeal carcinoma (esp. endemic subtype)

Others: p53 Mt, PI3K/AKT/mTOR & PTEN inactivation

Precursor lesions: Hyperplasia → Dysplasia → Carcinoma in situ → Invasive CA Leukoplakia – fixed white plaques; hyperparakeratosis w/hyperplasia Erythroplakia – red patches; often a/w epithelial dysplasia

Serotypes: -16 (>90%), -18 (NEJM 2001;344:1125)

Dx: p16 IHC (more sensitive), HPV in-situ hybridization (more specific), HPV DNA PCR

Location: Most commonly oropharyngeal

Demographics: Younger pt w/min. smoking/EtOH hx, p/w extensive nodal disease → w/u locates small oropharyngeal 1° tumor

Prognosis: Better than stage-matched HPV-negative tumors (NEJM 2010;363:24)

Hx – dysphagia, nutrition/wt loss, trismus/pain; EtOH, tobacco, sexual hx

Physical – Detailed H&N exam w/mirror exam or direct visualization. Consider triple endoscopy if unknown 1° or diffuse mucosal abnormalities

Imaging – CT/MRI of neck, chest imaging = CXR at minimum. Consider CT chest or PET/CT if N2 or N3 disease

Bx – after imaging if possible to avoid false (+), esp PET/CT; FNA of involved neck node well-tolerated, convenient; tissue HPV testing if oropharynx

Multidisciplinary care – rad onc, surgery, med onc; nutrition (PEG if malnutrition at baseline), dental, speech path, smoking/EtOH cessation

T stage is variable by site; N & M stages are more uniform

Stage I = T1; Stage II = T2; Stage III = T3 or N1 (single ipsilateral LN ≤ 3 cm)

Stage IV = still potentially curable

Nasopharyngeal staging system differs from other upper aerodigestive ca

HPV-associated more favorable than nonHPV; EGFR overexpression → worse

Surgery & RT alone (early stage) or together (more advanced stage) are mainstays; chemotherapy has ↑ role in latter

Surgical margins – clear = 5 mm or more; close margins <5 mm; (+) = CIS or invasive at margin; close/(+) may dictate changes to RT or chemo plan. No OS benefit to adjuvant chemo alone (MACH-NC, Radiother Oncol 2009;92:4)

RT – when surgery is not technically feasible or undesirable (eg, larynx preservation). SEs of RT – both short and long term- fatigue, xerostomia, 2° malignancies (sarcomas). EBRT standard 66-70 Gy, 2 Gy fractions to 1° tumor and/or high-risk LNs. “Hyperfractionation” = potential higher cumulative doses in smaller fractions. Increasingly, IMRT used to minimize xerostomia (Lancet Oncol 2011;12:127) and optimize targeting but longer planning, more expertise required.

Standard is concurrent CRT; used as alternative to surgery for organ preservation or improve outcomes for unresectable or high-risk, resected disease

Larynx preservation improved w/concurrent cisplatin + RT (RTOG 91-11, JCO 2013;epub)

Adjuvant cisplatin added during post-op RT ↑ DFS (NEJM 2004;350:1937) & OS (NEJM 2004;350:1945) if (+) margins or extracapsular extension in LN (Head Neck 2005;27:843)