Head and Neck Cancer - Board Review Summary

PART I - HPV+ OROPHARYNX

Management Paradigm + Dose Anchors

Clinical lane	Seconds-glance approach	Dose anchors
Early / low-volume	T1-2 N0 or selected single node <=3 cm: RT alone or surgery/TORS depending on exposure, laterality, functional tradeoffs, and chance of avoiding adjuvant therapy.	RT alone usually 68-70 Gy; selected hypofractionated 66-70 Gy at 2.1-2.2 Gy/fx. Elective neck 44-50 Gy sequential or 54-63 Gy SIB.
Locally advanced definitive	T3-4, multiple nodes, or node >3 cm: definitive CRT with cisplatin if eligible. Cetuximab is not equivalent to cisplatin.	Gross disease 70 Gy / 33-35 fx + cisplatin 100 mg/m2 q3wk or weekly 40 mg/m2.
Surgery-first / TORS path	Best for well-exposed, lateralized T1-2 tonsil/base-of-tongue tumors when surgery is likely to avoid triple-modality care. Pathology drives observation vs PORT vs POCRT.	Low risk observe; selected intermediate risk 50 Gy; usual intermediate 56-60 Gy; ENE/+margin 60-66 Gy + cisplatin.
Recurrent / metastatic / palliative	Use salvage surgery or re-irradiation only for carefully selected localized recurrence; otherwise systemic therapy and symptom-directed RT.	Palliation commonly 30 Gy / 10, 20 Gy / 5, 8 Gy x 1, or QUAD shot 14-14.8 Gy / 4 BID repeated if benefit.

TORS vs Primary RT/CRT

Trial	Design	Key results	Board takeaway
ORATOR	Phase II randomized trial, T1-2 N0-2 OPSCC, HPV+/-; RT 70 Gy +/- chemo vs TORS + neck dissection +/- adjuvant therapy.	MDADI at 1 year favored RT, but the difference did not meet the prespecified clinical threshold; 5-year swallowing converged and OS/PFS were excellent in both arms.	No survival-powered winner; toxicity spectra differ more than efficacy.
ORATOR2 / primary analysis	HPV+ only; de-escalated RT 60 Gy +/- weekly cisplatin vs de-escalated transoral surgery + neck dissection +/- reduced adjuvant RT.	Stopped early for excess mortality in surgical arm; de-escalated primary RT performed extremely well.	De-escalated surgery was not safe in this trial; be careful using surgery as a de-escalation shortcut.

High-yield TORS principle: choose the modality that uses the fewest treatment modalities necessary. Avoid triple-modality treatment whenever possible. TORS fits best for well-lateralized, well-exposed T1-2 tonsil/base-of-tongue tumors with low ipsilateral nodal burden; bulky N2-3 disease, obvious ENE, poor exposure, or infiltrative midline disease favors primary CRT.

Definitive RT Alone vs CRT

Clinical setting	Preferred approach	Supporting detail
T1-2 N0	RT alone reasonable	Excellent outcomes in carefully selected early-stage disease.
T1-2 N1, single node <=3 cm	RT alone acceptable in selected HPV+ cases	Especially when chemo is contraindicated.
T3-4 any N	CRT	Locally advanced standard.
>=2 nodes or single node >3 cm	CRT	Standard combined-modality approach.

RTOG 1016 established that cetuximab is inferior to cisplatin in HPV+ OPC. With accelerated IMRT 70 Gy / 35 fx / 6 wk, OS, PFS, and locoregional control all favored cisplatin, while severe toxicity was similar. Cisplatin + RT remains standard; cetuximab is for true cisplatin-ineligible patients. De-ESCALaTE HPV tells the same practical story.

Definitive Dose / Fractionation / Volumes

Scenario	Dose / fractionation	Notes
Gross disease with concurrent systemic therapy	70 Gy / 33-35 fx	Definitive standard.
Elective neck, sequential	44-50 Gy	Conventional elective range.
Elective neck, SIB	54-63 Gy	Typically 1.6-1.8 Gy/fx.
RT alone, conventional	68-70 Gy	T1-2 N0-1 single node <=3 cm.
RT alone, accelerated / hyperfractionated	68-72 Gy over 6 weeks or 74.4-81.6 Gy at 1.2 Gy BID	RT-alone intensification option, especially for T3-4 if no systemic therapy.

Elective Nodal Selection and Unilateral RT

Common elective levels: II-IV, retropharyngeal, and retrostyloid depending on nodal status.
Often omissible: level IB if no oral cavity involvement; level V if no naso/hypopharyngeal involvement.
Unilateral RT strong lane: HPV+ T1-2 palatine tonsil cancer confined to tonsillar fossa with no positive node or a single node <=3 cm and no ENE.
Bilateral RT required: base of tongue, soft palate, posterior pharyngeal wall, or tonsil tumors crossing midline / invading tongue base.

De-escalation: Failed Blanket Reduction, Selected Post-op Success

NRG-HN005 reminder: blanket definitive dose reduction failed. 60 Gy + cisplatin and 60 Gy + nivolumab did not demonstrate non-inferiority versus 70 Gy + cisplatin. HPV status and smoking history alone are not enough selection.

Investigational: biomarker-driven de-escalation remains active. The MSK 30 ROC hypoxia-guided pilot used FMISO PET to select candidates for 30 Gy / 15 fx + platinum, with excellent early locoregional control and low grade 3 RT-related mucositis/dysphagia. FDG-PET response, mid-RT CT nodal response, and ctHPV DNA kinetics remain trial-oriented.

Study	Key design	Main result	Takeaway
ECOG 3311	After TORS, low-risk observed; intermediate-risk randomized to 50 Gy vs 60 Gy; high-risk got 66 Gy + weekly cisplatin.	Long-term PFS remained excellent, including the 50 Gy intermediate-risk arm.	50 Gy is a key selected intermediate-risk postoperative HPV+ dose.
MC1675 / DART	Intermediate risk without ENE: de-escalated 30 Gy BID + weekly docetaxel vs standard; high-risk ENE cohort also randomized.	Intermediate-risk cohort had excellent control with lower toxicity/QOL gains; high-risk ENE cohort had worse PFS with de-escalation.	Aggressive de-escalation may work for favorable intermediate risk, but do not undertreat ENE-positive / pN2 disease.

Mucosal-sparing postoperative RT in select resected p16+ OPC treated only nodal regions and omitted the primary mucosal site. Two-year local and locoregional control were excellent with low PEG use. Promising, but selected rather than universal.

PART II - NASOPHARYNX CANCER

Management Paradigm + Dose Anchors

Clinical lane	Seconds-glance approach	Dose anchors
Early stage	T1N0 and selected low-risk T2N0: definitive RT alone; add chemo as risk increases.	Primary/gross disease 70 Gy; elective/high-risk volumes often 54-60 Gy.
Intermediate risk	CRT backbone for nodal or locally advanced disease that does not clearly require induction first.	70 Gy + concurrent cisplatin.
Locoregionally advanced	Bulky / EBV-high-risk stage III-IV: induction chemotherapy followed by CRT is the modern favored strategy. GP and TPF are key induction regimens.	After induction: residual GTV 70 Gy; resolved pre-IC soft-tissue GTV about 64 Gy; high-risk CTV 60-62 Gy; low-risk CTV 54-56 Gy.
Field de-escalation / adjuvant nuance	Selected N0-1 patients can spare the contralateral lower neck. Metronomic capecitabine is a real adjuvant option for selected high-risk patients after CRT.	Capecitabine 650 mg/m2 BID x 1 year. Do not undertreat initially involved skull base/bone from pre-IC imaging.

RT vs CRT vs IC-CRT

Trial	Design	Key result	Takeaway
Intergroup 0099	Stage III-IV NPC; RT alone vs RT 70 Gy + concurrent cisplatin then adjuvant PF.	Large PFS and OS improvement with combined modality.	Historic landmark establishing CRT-based intensification.
Chen 2012	CCRT + adjuvant PF vs CCRT alone.	No significant FFS or OS benefit.	Classic adjuvant PF after modern CCRT is controversial.
NPC-0502	Post-CRT EBV-positive patients; adjuvant GP vs observation.	No clear benefit.	EBV-selected adjuvant PF/GP has not clearly rescued AC.
Metronomic capecitabine	High-risk LA-NPC after CCRT +/- IC; capecitabine 650 mg/m2 BID x 1 year vs observation.	Improved FFS, OS, and DMFS.	One of the strongest positive adjuvant-era studies.
TPF IC	TPF x3 then CCRT vs CCRT alone.	Improved long-term survival.	Induction improves distant control and survival.
GP IC	Gemcitabine/cisplatin x3 then CCRT vs CCRT alone.	Improved recurrence-free and overall outcomes.	GP is a modern preferred induction regimen.
MAC-NPC	Network meta-analysis of combined-modality NPC strategies.	IC + CCRT ranked highest across key endpoints.	IC + CCRT is the preferred overall strategy in LA-NPC.

Practical framework: T1N0 and many low-risk T2N0 cases can still receive RT alone; CRT is the backbone for intermediate disease; and IC -> CRT is preferred for locoregionally advanced disease, especially bulky / EBV-high-risk presentations.

Elective Nodal Coverage and Post-Induction Volumes

Tang UNI vs WNI: selected N0-N1 NPC patients randomized to unilateral/upper-neck style irradiation vs whole-neck irradiation had non-inferior regional control with less late hypothyroidism, fibrosis, dysphagia, and carotid stenosis. Contralateral lower-neck recurrence was extremely rare.

Study	Strategy	Main result
Yang / Xiang phase III	Post-IC residual GTV got 70 Gy; resolved pre-IC GTV randomized to 70 Gy vs 64 Gy.	No disease-control/survival decrement; better xerostomia/cognitive outcomes with 64 Gy.
Tang 2025 reduced-volume RT	Post-IC soft-tissue GTV reduction vs conventional pre-IC GTV; 70 Gy GTV, 60-62 Gy high-risk CTV, 54-56 Gy low-risk CTV.	Non-inferior LRRFS with less mucositis, otitis, and xerostomia.

NPC de-escalation rule: post-IC soft-tissue response can guide radical-dose volume reduction, but bony structures with initial invasion should still be delineated from pre-IC imaging and treated aggressively.

PART III - EARLY GLOTTIC LARYNX

Management Paradigm + Dose Anchors

Clinical lane	Seconds-glance approach	Dose anchors
Tis / T1a N0	Definitive RT or transoral laser/microsurgery; single-vocal-cord or partial-larynx RT is increasingly attractive for well-selected T1a disease.	Classic RT 63 Gy / 28 preferred or 66 Gy / 33; selected hypofractionated 50-52 Gy. No elective neck for true glottic T1N0.
T1b / favorable T2 N0	Definitive RT remains a clean organ-preservation answer; partial-larynx approaches are less settled as volume and bilateral/anterior commissure involvement increase.	T2 range 64.8-70 Gy.
Unfavorable T2 N0	Impaired/sluggish cord mobility, bulky disease, subglottic extension, paraglottic concern, or substantial anterior commissure involvement may justify intensified RT or CRT discussion.	Gross dose 70 Gy if CRT-style; otherwise altered-fractionation RT to standard definitive dose.

T1N0 Partial Larynx / Single Vocal Cord RT

Study	Population	Local control / signal	Functional / toxicity signal
Erasmus MC / Tans	T1a mostly	Excellent 5-year LC.	Voice improved over time; low severe late toxicity.
Al-Mamgani	T1a N0	Very high early LC with single vocal cord irradiation.	Less acute toxicity and better voice than whole-larynx RT in selected patients.
Elsharief / MD Anderson series	T1a or selected Tis/T1-2 N0	Partial-larynx or SVCI appears oncologically strong for T1a; T2 is less secure.	Better voice, dysphagia, or MDADI signals in selected patients.

Main point: for T1a N0, partial-larynx or single-vocal-cord RT can achieve excellent control with better voice / acute-toxicity profiles. For T2, data are less secure and local control may be lower.

T2N0 Glottic: Add Chemo or Intensify RT?

T2N0 glottic disease has worse local control with RT alone than T1 disease, especially with impaired cord mobility, subglottic extension, anterior commissure involvement, or bulky GTV. There is no dedicated randomized phase III CRT-vs-RT trial for T2N0 glottic cancer.

Practical board takeaway: unfavorable T2 glottic cancer may justify treatment intensification through CRT or altered-fractionation/accelerated RT.

PART IV - LARYNX / HYPOPHARYNX, HPV-NEGATIVE: ELECTIVE NODAL DE-ESCALATION

Management Paradigm + Dose Anchors

Clinical lane	Seconds-glance approach	Dose anchors
Early glottic contrast	T1-2N0 glottic disease generally treats the larynx only; elective neck treatment is not routine because occult nodal risk is low.	Larynx-only definitive dose per early glottic table.
Supraglottic / hypopharynx elective neck	These sites have meaningful bilateral nodal risk; elective nodal treatment is standard for definitive organ-preservation cases.	Conventional elective neck 44-50 Gy sequential or 54-63 Gy SIB; de-escalated 40-43 Gy supported in selected modern series/trials.
Locally advanced organ preservation	Definitive CRT is a standard larynx-preservation strategy when surgery is avoidable and airway/swallowing function is appropriate.	Gross primary/nodes 70 Gy / 35 + cisplatin; elective dose as above.
Postoperative	PORT for adverse features; POCRT for positive margin or ENE.	Intermediate risk 54-60 Gy; high risk 60-66 Gy + cisplatin.

Why This Differs from Gross-Disease De-escalation

A key conceptual distinction: gross-disease de-escalation failed in HPV+ OPC because macroscopic tumor has a steep dose-response curve. Elective nodal de-escalation targets microscopic disease, where the dose-response curve is shallower and de-escalation is more plausible.

Study	Population / design	Elective dose	Main result
Nevens / Deschuymer / Nuyts	Belgian randomized experience, mostly HPV-negative HNSCC.	40 Gy vs 50 Gy	Very few true elective failures and lower salivary toxicity with 40 Gy.
UPGRADE-RT	Dutch randomized trial, RT-alone for oropharynx/larynx/hypopharynx.	43 Gy vs 50 Gy	Similar elective nodal recurrence with less acute grade 3+ dysphagia.
Sher phase II	Mixed HPV, most with concurrent chemo.	40 Gy / 20 + reduced elective volumes	No solitary elective nodal failures.
Zakeri 2025	HPV-negative larynx / hypopharynx / p16-negative OPC / CUP.	40 Gy elective with CRT	No solitary elective nodal recurrences; recurrences were in high-dose volumes.
DEPEND	HPV-negative stage IVA/B after neoadjuvant nivolumab + carboplatin/paclitaxel; deep responders omitted elective volumes.	0 Gy elective in responders	Promising 2-year PFS/OS with less mucositis, dermatitis, and dry mouth in de-escalated responders.

Guideline/practice position: conventional elective dose ranges remain 44-50 Gy sequential or 54-63 Gy SIB. A biologically equivalent elective range around 40-50 Gy to negative nodal regions is also evidence-supported in selected settings. Adoption is real but uneven.

PART V - ORAL CAVITY: PORT, CRT, AND PERIOPERATIVE IMMUNOTHERAPY

Management Paradigm + Dose Anchors

Clinical lane	Seconds-glance approach	Dose anchors
Early resectable	Surgery first with adequate margins and neck management based on depth/risk. Observation only when pathology is truly low risk.	No RT for clean low-risk pathology. PORT discussion for close margin, PNI/LVI, DOI-driven risk, poor differentiation, or other adverse features.
Intermediate-risk postop	PORT for close margins, pT3-4, pN2-3, level IV/V nodes, PNI, LVI, or adverse primary features.	Typical 54-60 Gy; start RT ideally within 6 weeks of surgery.
High-risk postop	Positive margin and/or ENE remain the cleanest board indication for postoperative CRT.	60-66 Gy + cisplatin 100 mg/m2 days 1/22/43 or weekly 40 mg/m2.
Resectable locally advanced	Perioperative pembrolizumab is an option for PD-L1 CPS >=1 resectable stage III-IVA HNSCC, integrated around surgery and adjuvant RT/CRT.	Adjuvant RT/CRT remains pathology-driven; pembrolizumab does not replace adequate surgery or indicated RT/CRT.

Surgery First, Then Pathology-Driven Adjuvant Therapy

Risk group	Features	Usual treatment implication
High risk	ENE and/or positive margin	Category 1 postoperative CRT
Intermediate risk	Close margins, pT3-4, pN2-3, level IV/V nodes, PNI, vascular invasion, lymphatic invasion	PORT, with selective discussion of systemic intensification.

Landmark Postoperative Trials

Trial	Design	Main result	Board takeaway
EORTC 22931	Post-op RT 66 Gy vs CRT with cisplatin 100 mg/m2 q3wk x3.	Improved OS, PFS, and locoregional control in very high-risk patients.	Post-op CRT clearly better in very high-risk disease.
RTOG 9501 / long-term	Post-op RT 60 Gy +/- cisplatin.	Long-term benefit mainly in ENE / positive margin subgroup.	>=2 nodes alone did not clearly benefit from cisplatin.
Bernier pooled 2005	Pooled EORTC + RTOG analysis.	ENE and/or positive margins were the features with consistent CRT benefit in both trials.	Created the modern ENE/+margin paradigm.
Zumsteg 2025	Updated combined analysis.	CRT improved cancer outcomes but increased other-cause mortality; challenged strict ENE/+margin-only predictiveness.	Important challenge to dogma, not a wholesale guideline replacement.

Current exam answer: ENE and positive margins remain the strongest category 1 indications for postoperative CRT. The 2025 pooled update is important, but it should be framed as a challenge to the paradigm rather than a replacement.

Modern Oral Cavity Nuance

Tian JCO 2024: in propensity-matched early oral tongue pT1-2N0M0 SCC, PORT improved outcomes in selected adverse-feature subgroups, especially moderate-to-poor differentiation. This is a testable modern nuance, not a universal guideline rewrite.

KEYNOTE-689 / FDA approval: perioperative pembrolizumab improved event-free outcomes in resectable locally advanced HNSCC and is FDA-approved for tumors with PD-L1 CPS >=1. Surgery and adjuvant RT/CRT remain standard components; pembrolizumab is integrated around them.

PART VI - SELECTED HEAD AND NECK QUICK HITS

Omission-Check Entities for Oral Boards

Entity / scenario	Board-review hook / RT role
HPV-negative oropharynx	No HPV-style de-escalation. Definitive CRT generally uses gross-dose 70 Gy + cisplatin when organ preservation is chosen; surgery-first cases follow pathology-driven PORT/POCRT logic.
Salivary gland malignancy	Surgery is primary when resectable. PORT is favored for T3-4, high grade, close/positive margins, PNI, nodal disease, recurrent disease, or adenoid cystic histology. Anchors: postop bed 60 Gy, positive margin/residual risk 66 Gy, gross/unresectable disease about 70 Gy. Cover involved named nerves toward skull base for clinical/radiographic PNI; do not add concurrent chemotherapy routinely outside trials.
Sinonasal malignancy	Histology-driven, usually surgery + PORT when resectable; definitive CRT for unresectable or selected organ-preservation cases. Postop dose commonly 60-66 Gy; definitive gross disease about 70 Gy. Protons can be useful when optic apparatus, brain, skull base, or orbit constraints threaten coverage.
SCC unknown primary	Workup: PET/CT, EUA/panendoscopy, directed biopsies, palatine tonsillectomy, and base-of-tongue mucosectomy when appropriate. HPV+ disease targets the oropharynx; EBV+ disease targets the nasopharynx; avoid reflex total-mucosal irradiation.
Recurrent / metastatic HNSCC	KEYNOTE-048 logic: pembrolizumab alone for PD-L1 CPS-positive patients when response can wait; pembrolizumab + platinum/5-FU when rapid response is needed or CPS is low/unknown. Consider local therapy for oligometastatic or oligoprogressive disease.
Palliative HN RT	Choose regimen by symptom urgency, prognosis, prior RT, and mucosal toxicity tolerance. Common anchors: 30 Gy / 10, 20 Gy / 5, 8 Gy x 1, or QUAD shot 14-14.8 Gy / 4 fx BID, repeated every 3-4 weeks if responding and tolerable.
Supportive care script	Before curative HN RT: dental evaluation/fluoride, smoking/alcohol cessation, nutrition, SLP/swallow exercises, pain plan, antiemetics, skin care, mask-anxiety plan, and candidiasis/secretions/constipation rescue plans. Long-term: thyroid, dental/ORN prevention, swallowing, carotid/vascular risk, hearing, and trismus surveillance.
Skull base / PNI pathways	Always ask about numbness, pain, diplopia, facial weakness, and trismus. Key routes: V2 via foramen rotundum, V3 via foramen ovale, VII via stylomastoid foramen/facial canal, and spread toward Meckel cave/cavernous sinus. Named-nerve PNI changes target design.

PART VII - LYMPH NODE COVERAGE AT A GLANCE

The framework

Patterns of nodal spread are predictable by primary site — most board questions hinge on knowing which levels are most likely involved and which are reliably spared for a given primary.
Elective coverage should match the highest-risk nodal regions and skip levels with consistently <5-10% subclinical risk to reduce toxicity.
Tumor biology shapes coverage as much as anatomy: p16+/HPV+ → oropharyngeal mucosa; EBV+ → nasopharyngeal mucosa; p16- / EBV- → broader mucosal coverage with comprehensive nodal coverage.
Modern AJCC/contouring nomenclature uses VIa/VIb (pretracheal/paratracheal) and VIIa/VIIb (retropharyngeal/retrostyloid). Older texts may use IRP, jugulodigastric, etc.

A. Cervical level anatomy — quick refresher

Level	Anatomic name	Key boundary / contents
Ia	Submental	Between anterior bellies of digastric, above hyoid.
Ib	Submandibular	Below mandible, above hyoid, anterior to posterior edge of submandibular gland.
II (IIa/IIb)	Upper jugular	Skull base → hyoid; divided by spinal accessory nerve (IIa anterior, IIb posterior).
III	Middle jugular	Hyoid → lower border of cricoid cartilage.
IV (IVa/IVb)	Lower jugular	Cricoid → clavicle; IVb extends into medial supraclavicular fossa.
Va / Vb	Posterior triangle (spinal accessory / transverse cervical)	Posterior to SCM; Va above lower border of cricoid, Vb below.
VIa	Anterior central / pretracheal	Includes the Delphian (prelaryngeal) node.
VIb	Paratracheal (recurrent laryngeal nerve)	Lateral to trachea along the RLN; bridges into upper mediastinum.
VIIa	Retropharyngeal	Behind pharynx, anterior to prevertebral fascia, skull base → ~C3.
VIIb	Retrostyloid	Posterior to styloid process; contains internal carotid and cranial nerves IX-XII.
VIII	Parotid (intraglandular + periparotid)	Drainage for scalp, ear, lateral face, anterior parotid skin malignancies.
IX	Buccofacial	Along facial vessels superficial to buccinator.
X (Xa/Xb)	Retroauricular / occipital	Drainage for posterior scalp, posterior ear.

B. Patterns of nodal spread by primary site

Primary site	Commonly involved levels	Rarely involved / often spared	Special pearl
Oral cavity (tongue, FOM, buccal, RMT, alveolus, hard palate, lip)	I, II, III ± IV	V, VI (rare), VIIa retropharyngeal (rare)	Oral tongue can have skip mets to III/IV without involving I-II. VIb paratracheal is rarely involved (<5%).
Oropharynx, HPV+ (tonsil, BOT, soft palate, PPW)	II, III, IV, often cystic; retropharyngeal in PPW/SP	I (uncommon), V (uncommon)	Well-lateralized tonsil with limited nodal burden can be ipsilateral only. BOT / soft palate / PPW require bilateral coverage.
Oropharynx, HPV-negative	II, III, IV, retropharyngeal more often	I, V uncommon	Higher retropharyngeal risk than HPV+ counterparts; lower cystic node frequency.
Nasopharynx (EBV+)	Retropharyngeal, II, V, then III/IV	I, VI rare in N0-1	Always bilateral. Retrostyloid (VIIb) and high level II are common initial sites.
Hypopharynx (pyriform sinus, post-cricoid, posterior pharyngeal wall)	II, III, IV, retropharyngeal, and VIb (paratracheal)	I (uncommon)	VIb paratracheal involvement 20-60% with post-cricoid or pyriform sinus apex disease. Always bilateral.
Supraglottic larynx	II, III, IV bilateral	I, V, VI uncommon	High rate of occult bilateral nodal disease (~30-40% even in cN0). Elective bilateral II-IV is standard.
Glottic larynx, T1-2 N0	None routinely (<10% nodal risk)	All levels	No elective neck for true T1-2 N0 glottic disease.
Glottic larynx, T3-4 or transglottic	II, III, IV bilateral	I, V uncommon	Subglottic extension or transglottic disease → add VIa/VIb (pretracheal/paratracheal).
Subglottic larynx	II, III, IV, VI (paratracheal especially), and upper mediastinum	I, V uncommon	Always include level VI and upper mediastinum.
Sinonasal / nasal cavity	Variable; Ib, II, retropharyngeal for posterior tumors	V rare	Many sinonasal malignancies are N0 at presentation; elective neck only for high-risk histologies (SCC, SNUC) or T3-4.
Parotid (salivary)	Intraglandular (VIII), Ib, II, III	IV, V uncommon	Adenoid cystic carcinoma and high-grade tumors → add nerve-pathway coverage (VII via stylomastoid foramen).
Submandibular (salivary)	Ib, II, III	V rare	For adenoid cystic, cover lingual / marginal mandibular / hypoglossal nerve pathways.
Cutaneous (head and neck skin SCC / melanoma)	Drainage-dependent; parotid (VIII), occipital (X), retroauricular for posterior scalp; Ib/II for facial	—	Always map drainage by anatomic location; consider SLN biopsy for cutaneous melanoma and high-risk cutaneous SCC.

C. Elective coverage recommendations by site (definitive RT)

Site / scenario	Elective levels to cover	Laterality
HPV+ tonsil, well-lateralized, T1-2 with ≤1 ipsilateral node ≤3cm, no ENE	Ipsilateral II-IV ± retropharyngeal	Ipsilateral only
HPV+ tonsil with contralateral risk, or BOT / soft palate / PPW	Bilateral II-IV + retropharyngeal	Bilateral
Oral cavity (all sites except lip)	I-III ipsilateral (bilateral I if near midline); ± IV for tongue / FOM	Ipsilateral; bilateral I for midline lesions
Hypopharynx, definitive	II-IV bilateral + retropharyngeal + VIb (paratracheal) for post-cricoid / pyriform apex	Bilateral
Nasopharynx (definitive)	II-V bilateral + retropharyngeal / VIIb; N0-1 can spare contralateral lower neck per Tang UNI vs WNI	Bilateral
Supraglottic larynx	II-IV bilateral	Bilateral
Glottic larynx, T1-2 N0	None (larynx only)	N/A
Glottic larynx, T3-4 or transglottic	II-IV bilateral; add VI for subglottic extension	Bilateral
Subglottic larynx	II-IV + VI (pre- and paratracheal) + upper mediastinum	Bilateral
SCC unknown primary, p16+ adenopathy in level II	Oropharyngeal mucosa + bilateral II-IV + retropharyngeal; spare larynx and hypopharynx per UF approach	Bilateral
SCC unknown primary, EBV+ adenopathy	Treat as nasopharynx: bilateral nasopharynx + II-V + retropharyngeal / VIIb	Bilateral

D. Special situations and high-yield trial anchors

D'Cruz NEJM 2015 — Elective vs therapeutic neck dissection in cT1-2 N0 oral cavity SCC: pivotal phase III RCT (majority oral tongue) randomizing upfront END vs observation with salvage neck dissection at recurrence. END improved both DFS (69.5% vs 45.9%, p<0.001) and 3-year OS (80.0% vs 67.5%, HR 0.64). Occult pN+ rate in the END arm was 29.6%. END is the surgical standard for cT1-2 N0 oral cavity SCC, especially with DOI >3 mm. For primary-RT lanes, elective irradiation of levels I-IV is the radiation analog.

SCC unknown primary — University of Florida 2021 series: 50 patients with SCCA-UP and predominant adenopathy in level IIA, N1-2c disease, treated with RT volumes that deliberately spared the larynx and hypopharynx (oropharynx and nasopharynx targeted). With median follow-up 7.1 years, no patient developed mucosal recurrence (0/50). Supports oropharynx-focused (rather than total-mucosal) RT for typical SCCUP presentations.

SCC unknown primary — workup and mucosal-site assignment by tumor biology:

p16+ / HPV+ adenopathy: oropharynx is the overwhelmingly likely primary. The oropharynx (which includes the palatine tonsils) is the most likely primary site for HPV-driven occult SCC. Treat oropharyngeal mucosa (palatine tonsils + base of tongue) + bilateral nodal levels; spare larynx, hypopharynx, and nasopharynx.
EBV+ adenopathy: treat as nasopharyngeal primary (bilateral nasopharynx + standard NPC nodal coverage including retropharyngeal and retrostyloid).
p16-negative / EBV-negative adenopathy: traditional comprehensive mucosal RT (oropharynx + larynx + hypopharynx ± nasopharynx) has been the historical standard, but selected ipsilateral-only or oropharynx-focused approaches are increasingly used after thorough workup.
Workup must include: PET-CT before biopsy (reduces false-positive inflammatory uptake), EUA with directed biopsies, palatine tonsillectomy, and base-of-tongue mucosectomy (TORS) when feasible — primary identification rates increase substantially with mucosectomy.

Level VIb (paratracheal) trap: rarely involved (<5%) in oral cavity primaries, but involved in 20-60% of hypopharyngeal carcinomas, particularly with post-cricoid region or pyriform sinus apex involvement. Also routinely involved in subglottic larynx and high-risk thyroid disease. Don't reflexively cover VIb for oral cavity, but don't miss it for low hypopharynx / subglottic disease.

Retropharyngeal (VIIa) coverage: always include for nasopharynx, posterior pharyngeal wall, soft palate, hypopharynx, and HPV-negative oropharynx. For HPV+ tonsil with ipsilateral lateralized disease, retropharyngeal coverage is selective. The retropharyngeal space extends from skull base to ~C3 (upper border of hyoid).

Retrostyloid (VIIb) coverage: critical for nasopharynx and high level II / upper retropharyngeal involvement. Contains internal carotid and cranial nerves IX-XII — always inspect for high-level extension on imaging.

Skip metastases: oral tongue cancers can metastasize to level III/IV without involving level I or II ("skip mets"). For this reason, elective nodal coverage for oral tongue should include levels I-IV even when imaging shows only proximal nodal involvement.

Glottic exceptionalism: true T1-2 N0 glottic carcinomas have <10% nodal involvement due to sparse subepithelial lymphatics at the true vocal cord. This is the key reason elective nodal RT is omitted for early glottic disease — in contrast to nearly every other H&N mucosal site.

CROSS-CUTTING HIGH-YIELD POINTS

ORS / TORS vs RT in HPV+ OPC: ORATOR and ORATOR2 directly randomized surgery vs RT/CRT, but there is still no survival-powered phase III head-to-head winner.
RTOG 1016 / De-ESCALaTE: cetuximab is inferior to cisplatin in HPV+ OPC and should not replace cisplatin in eligible patients.
HPV+ definitive standard: gross disease 70 Gy / 33-35 fx with cisplatin.
RT alone in HPV+ OPC: acceptable mainly for T1-2 N0-1 with a single node <=3 cm or when chemo is contraindicated.
NRG-HN005: unselected definitive dose reduction to 60 Gy failed; blanket de-escalation is not standard.
Unilateral RT in HPV+ tonsil: reasonable when well lateralized and low nodal burden; BOT / soft palate / PPW / midline disease requires bilateral treatment.
ECOG 3311: postoperative 50 Gy is a key selected intermediate-risk HPV+ dose after TORS.
MC1675: aggressive postoperative de-escalation may work in intermediate-risk disease, but ENE-positive patients did worse with overly reduced therapy.
NPC systemic backbone: CCRT remains essential, but modern data favor IC + CCRT over CCRT + AC overall.
NPC adjuvant nuance: classic PF after CCRT is controversial, but metronomic capecitabine is a positive adjuvant study.
NPC nodal coverage: upper/unilateral-neck approaches can safely spare the contralateral lower neck in selected N0-1 patients.
Post-IC NPC planning: residual soft-tissue GTV can guide the 70 Gy volume, but initially involved bone should still be respected from pre-IC imaging.
T1a glottic cancer: partial-larynx / single-vocal-cord RT is increasingly compelling, with excellent control and better voice / toxicity outcomes.
T2 glottic cancer: worse local control than T1; consider intensified RT or CRT for unfavorable features.
HPV-negative larynx/hypopharynx elective de-escalation: randomized data now support 40-43 Gy as a safe elective dose in selected settings.
Oral cavity surgery-first principle: ENE and positive margins remain the strongest indications for postoperative CRT.
KEYNOTE-689: perioperative pembrolizumab is the first major perioperative immunotherapy advance for resectable LA HNSCC and is FDA-approved for PD-L1 CPS >=1 disease.
Curative HN RT starts before sim: dental/fluoride, nutrition, SLP/swallow exercises, smoking/alcohol cessation, pain plan, mask-anxiety strategy, and rescue plans matter.
Named-nerve PNI is a target-design problem: know V2/foramen rotundum, V3/foramen ovale, VII/stylomastoid-foramen/facial-canal routes, and when to cover toward Meckel cave/cavernous sinus/skull base.
SCC unknown primary: PET/CT + EUA/panendoscopy + directed biopsies/tonsillectomy/BOT mucosectomy; HPV+ points to oropharynx, EBV+ to nasopharynx; avoid reflex total-mucosal irradiation.
Palliative HN RT anchors: 30 Gy / 10, 20 Gy / 5, 8 Gy x 1, or QUAD shot 14-14.8 Gy / 4 BID repeated if beneficial.

CONSOLIDATED DOSE TABLE

Setting	Dose / regimen	Why it matters
HPV+ OPC definitive CRT	70 Gy / 33-35 fx	Modern standard gross-disease dose.
HPV+ OPC elective neck, sequential	44-50 Gy	Common conventional elective range.
HPV+ OPC elective neck, SIB	54-63 Gy	SIB elective range.
HPV+ OPC RT alone	68-70 Gy	Early-stage / chemo-ineligible approach.
30 ROC pilot	30 Gy / 15 fx	Investigational hypoxia-guided major de-escalation.
ECOG 3311 intermediate risk	50 Gy	Key selected postoperative HPV+ dose.
Post-op HPV+ high risk	60-66 Gy	Positive margin / ENE range.
NPC gross disease	70 Gy	Backbone definitive dose.
NPC resolved pre-IC GTV	64 Gy	Phase III-supported reduced dose to resolved pre-IC soft tissue.
NPC high-risk CTV	60-62 Gy	Reduced-volume phase III schema.
NPC low-risk CTV	54-56 Gy	Conventional low-risk dose.
Early glottic T1 N0	63 Gy / 28	Common preferred definitive regimen.
Early glottic T1 N0 alternative	50-52 Gy	Hypofractionated option.
Glottic T2 N0	64.8-70 Gy	Standard definitive RT range.
HPV-negative elective nodal de-escalation	40-43 Gy	Supported by Nevens/Nuyts and UPGRADE-RT.
Oral cavity intermediate-risk PORT	54-60 Gy	Close margin, PNI/LVI, pT3-4, pN2-3, level IV/V nodes.
Oral cavity high-risk postoperative RT	60-66 Gy	Positive margin / ENE range.
Post-op concurrent cisplatin	100 mg/m2	Days 1, 22, 43 standard schedule; weekly 40 mg/m2 is common.
Salivary gland PORT	60 Gy	Surgical bed / high-risk postoperative target.
Salivary positive margin / residual risk	66 Gy	Escalate highest-risk postoperative subvolume.
Salivary or sinonasal gross unresectable disease	~70 Gy	Definitive gross-disease anchor.
Sinonasal PORT	60-66 Gy	Postoperative microscopic/high-risk disease.
SCCUP gross nodal disease	66-70 Gy	Definitive gross-dose range.
SCCUP mucosal/elective risk volumes	44-60 Gy	Depends on HPV/EBV status, suspicion level, field size, and systemic therapy.
Palliative HN RT	30 Gy / 10, 20 Gy / 5, 8 Gy x 1	Symptom-directed common regimens.
QUAD shot	14-14.8 Gy / 4 fx BID	Repeat every 3-4 weeks if response and tolerance are good.

KEY LANDMARK TRIALS (MEMORIZE)

Trial	Disease	One-line takeaway
ORATOR	HPV+/- OPSCC	TORS and RT both work; functional tradeoffs differ more than control outcomes.
ORATOR2	HPV+ OPSCC	De-escalated surgery arm had excess mortality; de-escalated RT was strong.
RTOG 1016	HPV+ OPC	Cetuximab is inferior to cisplatin with RT.
NRG-HN005	HPV+ OPC	Blanket definitive dose de-escalation to 60 Gy failed.
ECOG 3311	Post-op HPV+ OPC	50 Gy is a key selected intermediate-risk postoperative dose after TORS.
MC1675 / DART	Post-op HPV+ OPC	Aggressive de-escalation may work in favorable intermediate risk, but not safely in higher-risk ENE disease.
Intergroup 0099	NPC	Established CRT-based intensification as the landmark standard.
Chen 2012	NPC	Adjuvant PF after CCRT did not clearly improve outcomes.
Metronomic capecitabine	NPC	Adjuvant capecitabine improved FFS, OS, and DMFS.
TPF / GP	NPC	Induction chemotherapy before CCRT improves outcomes; GP is a modern preferred regimen.
Tang UNI vs WNI	NPC nodal coverage	Upper/unilateral-neck sparing is non-inferior in selected N0-1 patients and reduces late toxicity.
Tang 2025 reduced-volume RT	NPC post-IC planning	Post-IC reduced-volume RT is non-inferior and less toxic.
UPGRADE-RT	HPV-negative HN elective neck	43 Gy elective dose is safe and less toxic than 50 Gy.
Nevens / Nuyts	HPV-negative HN elective neck	40 Gy elective dose produced very few true elective failures.
EORTC 22931	Post-op HNSCC	CRT improved OS, PFS, and locoregional control vs RT alone.
RTOG 9501	Post-op HNSCC	Long-term CRT benefit was strongest in ENE / positive-margin disease.
Bernier pooled	Post-op HNSCC	Created the ENE/+margin paradigm for category 1 postoperative CRT.
Zumsteg 2025	Post-op HNSCC	Challenges the strict ENE/+margin-only paradigm, but with toxicity tradeoffs.
D'Cruz NEJM 2015	cT1-2 N0 oral cavity SCC	Upfront elective neck dissection improved DFS and OS vs observation; 29.6% occult pN+.
UF SCCUP 2021	SCC unknown primary, level IIA adenopathy	Sparing larynx/hypopharynx from RT volumes produced 0% mucosal recurrences.
KEYNOTE-689	Resectable locally advanced HNSCC	Perioperative pembrolizumab improved EFS and is FDA-approved for PD-L1 CPS >=1 disease.
KEYNOTE-048	R/M HNSCC	Pembrolizumab alone or with platinum/5-FU established first-line immunotherapy-based treatment.
Tian 2024	Early oral tongue SCC	PORT may help selected pT1-2N0 patients with adverse features, especially moderate-poor differentiation.