Anatomy, Staging and Work up

1. Head & Neck
• Anatomy With Lymphatic Drainage
• Etiology of Head And Neck Cancer
• Role Of HPV And EBV Virus
• Pathology & Prognostic Factors
Presenter : Dr. Varshu Goel
First Year Post-Graduate Resident
Department of Radiotherapy
Maulana Azad Medical College, Delhi

2. • Global incidence - exceeds half a million cases with around
300,000 deaths each year
(Chaturvedi et al, J Clin Oncol. 2013)
• In India – most common cancer in males and the fifth most
common in females
(International Agency for Research on Cancer GLOBOCAN, 2012)
• 90% of all head and neck cancers are squamous cell
carcinomas (HNSCC)
(Global Cancer Statistics, CA Cancer J Clin. 2011)
2
Introduction

3. Head & Neck
• Anatomy With Lymphatic Drainage
• Etiology of Head And Neck Cancer
• Role Of HPV And EBV Virus
• Pathology & Prognostic Factors

4. Gray’s Anatomy for Students, 3rd ed.

5. 5
NasalCavity
• Includes Septum, Floor, Lateral Wall & Vestibule
• The normal lining of the nasal cavity is pseudostratified
columnar ciliated epithelium except for the vestibule, that
comprises squamous epithelium with sweat and sebaceous
glands.
• Boundaries :
• Superior - cribriform plate of the ethmoidal bone with
olfactory apparatus
• Inferior - hard palate
• Anterior - nasal bones and cartilage that form the external
nose
• Posterior - posterior border of the hard palate and maxillary
sinus
• Lateral - formed from the medial walls of the maxillary sinus
inferiorly and the ethmoid sinus superiorly; three turbinates

6. 6
Atlas of Human Anatomy, 6th ed.
The Medial Wall Of The Nasal Cavity (Nasal Septum)

7. 7
Atlas of Human Anatomy, 6th ed.
The Lateral Wall Of The Nasal Cavity

8. 8
ParanasalSinuses
a) Maxillary sinuses - Largest, 15
ml volume
b) Ethmoidal Sinuses - Anterior,
Middle & Posterior group
c) Frontal Sinuses
d) Sphenoidal Sinus
• Sinuses are lined with
pseudostratified ciliated
columnar epithelium
• The purpose of the paranasal
sinuses is to lighten the bone
and give resonance to the voice
A. The position of the paranasal sinuses
in relation to the face.
B. Coronal section through the nasal
cavity showing the ethmoidal and the
maxillary sinuses Snell’s Clinical Anatomy by Regions, 9th ed.

9. The Lateral Wall Of The Nasal Cavity
Bulla Ethmoidalis

10. 10
Atlas of Human Anatomy, 6th ed.
The Medial Wall Of The Nasal Cavity (Nasal Septum)

11. 11
Gray’s Anatomy, 41st ed.
Lymphaticsof the NasalCavity
The lymphatic drainage of the nasal
cavity can be divided into two.
1. The main part of the nasal
cavity drains via the
nasopharynx to the
retropharyngeal nodes and
upper deep cervical nodes
(levels IIA and IIB).
2. The lower anterior portion
drains to the submandibular
(level IB), parotid (preauricular)
and jugulodigastric (level IIA)
nodes.
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

12. • Lymphatic drainage is typically
towards the retropharyngeal
(Rouviere’s node) and upper
deep cervical nodes (level II)
unless the tumour is
particularly anteriorly placed
when the buccinator, level I
and IIA nodes are at risk.
• The lymph system is
remarkably sparse and, as
such, tumours can be quite
advanced without involved
nodes.
12
Lymphaticsof the ParanasalSinuses
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

13. • Squamous cell carcinoma – originating from the mucosal
epithelium and includes a keratinizing and a non-keratinizing
type
• Lymphoepithelioma - poorly differentiated squamous cell
carcinoma or histologically undifferentiated carcinoma
accompanied by a prominent reactive lymphoplasmacytic
infiltrate; EBV associated
• Sinonasal undifferentiated carcinoma - aggressive and
distinctive carcinoma of uncertain histogenesis that typically
presents with locally extensive disease; composed of
pleomorphic tumour cells with frequent necrosis
• Adenocarcinoma - glandular malignancies of the sinonasal
tract, excluding defined types of salivary gland carcinoma 13
WHOhistologicalclassificationof Nasal
Cavityand ParanasalSinuses
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

14. • Salivary gland-type carcinomas
• Neuroendocrine tumours (carcinoids)
• Benign epithelial tumours
• Sinonasal papillomas
• Salivary gland-type adenomas
• Soft tissue tumours
• Haematolymphoid tumours
• Neuroectodermal tumors (pNETs)
• Tumours of bone and cartilage
• Secondary tumours
14
WHOhistologicalclassificationof Nasal
Cavityand ParanasalSinuses
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

15. • 12 cm from base of
skull to C6 vertebrae
Naso-pharynx –C1 &
C2 vertebra
Oro-pharynx - C2 &
C3 vertebrae
Hypo-pharynx - C4, C5
& C6 Vertebra
15
Pharynx
Gray’s Anatomy for Students, 3rd ed.

16. Nasopharynx
16
• Begins at the posterior
choana and extends along
the plane of the airway to the
level of the free border of the
soft palate
• Boundaries:
Superiorly – Basilar portion
of sphenoid & clivus
Lateral Walls (including the
Eustachian tube opening,
fossae of Rosenmuller and
the mucosa covering the
torus tubarius)
Posterior Wall formed by
Pharyngobasilar fascia
• Floor - formed by superior
surface of soft palate
Johann Christian Rosenmuller, 1808
Seventy to 90% of cases have nodes at some point. Levels IA/B are rarely
involved while levels II and V (the post-cervical chain) can be considered the
first involved nodes for this tumour site.
Gray’s Anatomy for Students, 3rd ed.

17. Normally, lined by pseudostratified columnar ciliated epithelium
• Nasopharyngeal (squamous cell) carcinoma
• Nasopharyngeal papillary adenocarcinoma
• Salivary gland-type carcinomas
• Benign epithelial tumours
• Soft tissue tumours
• Haematolymphoid tumours
• Tumours of bone and cartilage
• Secondary tumours
17
WHOhistologicalclassificationof
Nasopharynx
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

18. 18
Gray’s Anatomy for Students, 3rd ed.
Base of the Skull

19. Snell’s Clinical Anatomy by Regions, 9th ed.
Oral Cavity extends from skin–vermilion junction of the lips to the junction of the hard
and soft palate above and to the line of circumvallate papillae below.
OralCavity
Includes:
Mucosal Lip - Upper And
Lower Lip
Buccal Mucosa
Upper And Lower
Alveolar Ridge
Retromolar Trigone -
mucosa overlying the
ascending ramus of the
mandible from the level of
the posterior surface of the
last molar tooth to the apex
superiorly, adjacent to the
tuberosity of the maxilla
19

20. OralCavity
Includes:
Floor of the Mouth -
overlying mylohyoid and
hyoglossus; posterior boundary
is the base of the anterior pillar
of the tonsil; contains the ostia
of the submandibular and
sublingual salivary glands
Hard Palate
Anterior Two-Thirds of the
Tongue (Oral Tongue) - from
the line of circumvallate
papillae to the undersurface of
the tongue at the junction of
the floor of the mouth; four
parts : tip, lateral borders,
dorsum and undersurface
(nonvillous ventral surface of
the tongue).
20

21. 21
Lymphaticsof the LowerLip
• Nodal involvement in
cancers of the lip
occurs rarely (<5% at
presentation) but the
incidence is higher
with large, poorly
differentiated tumours
or those at the angle of
the mouth
• The neck nodes can be
a site of potential
relapse and therefore
must be included in
follow-up assessment
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

22. • Nodal involvement is usually
primarily to the submental
and submandibular glands
followed by the upper deep
cervical nodes, i.e. levels IA,
IB and II, though disease can
spread directly to levels III
and IV, so-called ‘skip’
nodes
• Midline tumours may
develop bilateral nodal
spread
Lymphaticsof the OralCavity
Walter & Miller’s Textbook of Radiotherapy, 7th ed.
22

23. Oropharynx
23
• Extending from the plane of the superior surface of the soft palate
to the superior surface of the hyoid bone (or vallecula)
• Includes : Base Of The Tongue, Inferior (Anterior) Surface Of The
Soft Palate And The Uvula, Anterior And Posterior Tonsillar Pillars,
Glossotonsillar Sulci, Palatine Tonsils, Lateral And Posterior
Pharyngeal Walls
Gray’s Anatomy for Students, 3rd ed.

24. • 60% of oropharyngeal cancers have nodal involvement at
presentation.
• Tonsillar cancers drain to the adjacent jugulodigastric or
subdigastric node (the so-called ‘tonsillar node’) and then the
remainder of the deep cervical nodes of level II and III.
• The remainder of oropharyngeal cancers are midline structures
and therefore can drain to bilateral nodes.
• Tumours of the soft palate and posterior pharyngeal wall drain to
the retropharyngeal nodes and upper deep cervical lymph nodes,
i.e. level II.
• Base of tongue tumours commonly spread to the mid and upper
cervical nodes, i.e. levels II and III.
Lymphaticsof the Oropharynx
24
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

25. Normally, Oral cavity and Oropharynx are lined by non-keratinized stratified
squamous epithelium except dorsum of the tongue, hard palate and attached
gingiva lined by keratinized squamous epithelium.
• Squamous cell carcinoma
• Lymphoepithelial carcinoma
• Epithelial Precursor lesions
• Benign epithelial tumours
• Soft tissue tumours
• Haematolymphoid tumours
• Salivary gland tumors
• Mucosal Malignant Melanoma
• Secondary tumours
25
WHOhistologicalclassificationof OralCavity
and Oropharynx
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

26. Larynx
• Extend from C3 to C6
• Supraglottis –epiglottis,
Aryepiglottic folds
(laryngeal aspect),
Arytenoids, Ventricular
bands (false cords)
• Glottis - True vocal cords
with anterior and
posterior commissures
• Subglottis : 2 cm long
and extends from 5 mm
below the free edge of
the true vocal cords to
the lower margin of
cricoid cartilage
26
Atlas of Human Anatomy, 6th ed.

27. Larynx
• The adult larynx is
lined entirely by
squamous epithelium,
with the exception of
the ventricles and the
subglottis which are
lined by respiratory
(pseudostratified
columnar ciliated)
epithelium .
• Initially, lymphatic
spread is upwards to
the jugulodigastric
lymph nodes
immediately beneath
the angle of the jaw.
Tumours also
commonly spread to
the mid-jugular lymph
nodes.
27
Atlas of Human Anatomy, 6th ed.

28. 28
Atlas of Human Anatomy, 6th ed.

29. Hypopharynx
• Extending from the plane of the
superior border of the hyoid
bone (or vallecula) to the plane
corresponding to the lower
border of the cricoid cartilage
• Includes :
Postcricoid Region - forming the
anterior wall of the hypopharynx
Lateral Hypopharyngeal Wall
Pyriform Sinuses (Right And
Left) : bounded by lateral
pharyngeal wall; and medially -
lateral surface of aryepiglottic
fold and the arytenoid and
cricoid cartilages (75% lesions)
Posterior Hypopharyngeal Wall -
from the level of the superior
surface of the hyoid bone to the
inferior border of the cricoid
cartilage
Gray’s Anatomy for Students, 3rd ed.
29
The hypopharynx is typically lined by
nonkeratinizing stratified squamous
epithelium

30. • The hypopharynx has an
extensive lymphatic supply.
• The majority of piriform fossae
cancers have nodal
involvement at presentation.
There is early spread to the
upper and mid deep cervical
nodes (level II and III) but the
drainage can include all levels
including the supraclavicular
nodes. Spread can be bilateral.
• The posterior pharyngeal wall
drains to the retropharyngeal
nodes and deep cervical
lymph nodes.
• The post-cricoid region drains
to levels III, IV and the
paratracheal nodes (level VI).
Lymphaticsof the
Hypopharynx
30
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

31. • Squamous cell carcinoma
• Verrucous carcinoma
• Basaloid squamous cell carcinoma
• Papillary squamous cell carcinoma
• Spindle cell carcinoma
• Acantholytic squamous cell carcinoma
• Adenosquamous carcinoma
• Lymphoepithelial carcinoma
• Giant cell carcinoma
• Malignant salivary gland-type tumours 31
WHOhistologicalclassificationof
Hypopharynxand Larynx
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

32. • Neuroendocrine tumors
• Benign epithelial tumours
• Soft tissue tumours
• Haematolymphoid tumours
• Tumours of bone and cartilage
• Mucosal Malignant Melanoma
• Secondary tumours
32
WHOhistologicalclassificationof
Hypopharynxand Larynx
WHO Classification Of Head & Neck Tumors, IARC Press, 2005

33. 33
Atlas of Human Anatomy, 6th ed.

34. • Retropharyngeal Space – infection spreads to posterior
triangle
• Prevertebral Space - between the prevertebral fascia and the
vertebral column; infection can travel to axilla via axillary
sheath
• Parapharyngeal space (PPS) - anterior to the styloid process
(prestyloid) that extends from the skull base to the level of the
angle of the mandible; contains primarily deep lobe of parotid
gland, fat, vascular structures, and small branches of the
mandibular division of the fifth cranial nerve
• Poststyloid space or carotid space (CS) : enclosed fascial
space located posterior to the styloid process; contains the
internal carotid artery, internal jugular vein, cranial nerves IX–
XII and lymph nodes.
• Masticator space - consists of muscles of mastication
(masseter, pterygoids, and temporalis)
34
Tissue Spaces In The HeadAnd Neck

35. c
c
35
Infrahyoid transverse section of the neck
Gray’s Anatomy, 41st ed.

36. 36
Vertical section of the body of the mandible close to the
angle showing the masticator space
Snell’s Clinical Anatomy by Regions, 9th ed.

37. 37
Atlas of Human Anatomy, 6th ed.
• Infratemporal fossa : wedge shaped space below middle
cranial fossa, deep to the ramus of the mandible and posterior
to the maxilla on each side of the skull, located between the
pterygoid process and the maxillary tuberosity
• Pterygopalatine fossa : pyramidal space located deep to
infratemporal fossa and below the apex of the orbit
• Pterygoid fossa : V-shaped fossa enclosed between lateral and
medial pteryoid plates diverging behind

38. Lymphatic
Drainage:
Neck Nodes
Walter & Miller’s Textbook of Radiotherapy, 7th ed.
38

39. 39
Superiorly – Mylohyoid m.
Posteriorly-
Body of hyoid
Medially -
Anterior
belly of C/L
digastric
muscle
Laterally -
Anterior
belly of
ipsilateral
digastric
muscle
LevelIA
Drains the skin of the chin,
the mid-lower lip, the tip of
the tongue, and the anterior
floor of the mouth
Submental
Nodes
Anteriorly –
Symphysis
menti
Inferiorly-
Platysma M
V. Grégoire et al., Radiotherapy and Oncology (2013)

40. 40
Superiorly - Body
of mandible
Posteriorly-
Posterior belly
of digastric
muscle
Medially-
Anterior
belly of
digastric
muscle
Laterally-
Stylohyoid
muscle
LevelIB
Drains lymphatics from the
submental lymph nodes (level
Ia), the lower nasal cavity, the
hard and soft palate, the
maxillary and mandibular
alveolar ridges, the cheek, the
upper and lower lips, and most of
the anterior tongue
Submandibular
Nodes
V. Grégoire et al., Radiotherapy and Oncology (2013)
Anteriorly –
Symphysis
menti
Inferiorly-
Platysma M

41. 41
Superiorly - Caudal edge of the
lateral process of C1
Inferiorly -
Horizontal
plane defined
by the inferior
border of the
hyoid bone
Anteriorly -
posterior
edge of
posterior
belly of
digastric m
Posteriorly-
Vertical
plane
defined
by the spinal
accessory
nerve
LevelIIA
V. Grégoire et al., Radiotherapy and Oncology (2013)
Laterally -
medial
surface of
sternocleido
mastoid
Medially-
Medial
edge of
internal
carotid
artery/scal
enius m.

42. 42
Superiorly - Caudal edge of the
lateral process of C1
Inferiorly -
Horizontal
plane defined
by the inferior
border of the
hyoid bone
Anteriorly -
Vertical
plane
defined by
the
spinal
accessory
nerve
Posteriorly
- Lateral
border of
the
sternocleid
omastoid
muscle
LevelIIB
Drains face, the parotid gland,
and the submandibular,
submental and retropharyngeal
nodes; the nasal cavity, the
pharynx, the larynx, the
external auditory canal, the
middle ear, and the sublingual
and submandibular glands
Upper Jugular
Group (IIA &
IIB)
V. Grégoire et al., Radiotherapy and Oncology (2013)
Medially- Medial edge
of internal carotid
artery/scalenius m.
Laterally -
medial
surface of
sternocleido
mastoid

43. 43
Superiorly - Caudal edge of the
body of the hyoid bone
Inferiorly -
Caudal edge of
cricoid cartilage
Anteriorly-
Anterior
edge of
sternocleid
omastoid
Laterally -
Deep
(medial)
surface of
sternocleid
omastoid
m.
LevelIII
Drains levels II and V, and
retropharyngeal,
pretracheal and recurrent
laryngeal nodes; the base of
the tongue, tonsils, larynx,
hypopharynx and thyroid
gland
Middle Jugular
Group
V. Grégoire et al., Radiotherapy and Oncology (2013)
Medially- Medial edge of
common carotid
artery/scalenius m.
Posteriorly
- Posterior
edge of
sternocleid
omastoid

44. 44
Superiorly - Caudal edge
of cricoid cartilage
Inferiorly - 2 cm
cranial to sternal
manubrium
Medially -
Medial
edge of
common
carotid
artery/later
al edge of
thyroid
gland/Scale
nius m.
Laterally -
Deep
(medial)
surface of
sternocleido
mastoid
LevelIVA
Drains levels III and V,
retropharyngeal, pretracheal,
and recurrent laryngeal nodes,
and the hypopharynx, larynx,
and thyroid gland.
Lower Jugular
Group
V. Grégoire et al., Radiotherapy and Oncology (2013)
Anteriorly-
Anterior
edge of
sternocleid
omastoid
Posteriorly
- Posterior
edge of
sternocleid
omastoid

45. 45
Superiorly - Caudal border of level IVa
(2 cm cranial to sternal manubrium)
Inferiorly -
Cranial edge of
sternal
manubrium
Medially - Lateral border of
level VI (pre-tracheal
component)/medial
edge of common
carotid artery
Laterally -
Lateral edge
of scalenius
m.
LevelIVB
Drains levels IVa and Vc, the
pretracheal, and recurrent
laryngeal nodes, the
hypopharynx, esophagus, larynx,
trachea and thyroid gland
Medial
Supraclavicular
Group
V. Grégoire et al., Radiotherapy and Oncology (2013)
Anteriorly-
Deep
surface of
sternocleid
omastoid
m./deep
aspect of
clavicle
Posteriorly- Apex of
Lung, brachiocephalic
Vein, brachiocephalic
trunk (right side) &
common carotid artery
and subclavian artery
on the left side

46. 46
Superiorly - Cranial edge of the
body of hyoid bone
Inferiorly - Plane just
below transverse
cervical vessels
Anteriorly-
Posterior
edge of
sternocleid
omastoid
m.
Posteriorly-
Anterior
border of
trapezius m.LevelV
VA includes the spinal accessory
nodes and VB includes nodes
following the transverse cervical
vessels & supraclavicular nodes, with
exception of Virchow node (level IV);
Surgically, level V is subdivided into
upper (Va) and lower (Vb) nodes
according to their respective
relationships with the cricoid
cartilage
Posterior
Triangle Group
(VA & VB)
V. Grégoire et al., Radiotherapy and Oncology (2013)
Laterally -
Platysma
m./skin
Medially - Levator
scapulae m./scalenius m.
Drains occipital and
retro auricular
nodes, the occipital
and parietal scalp,
the skin of the
lateral and posterior
neck and shoulder,
the nasopharynx,
the oropharynx and
the thyroid gland

47. 47
Superiorly - Plane just below
transverse cervical vessels (caudal
border of level V)
Inferiorly - 2 cm
cranial to sternal
manubrium, i.e.
caudal border of
level IVa
Anteriorly-
Skin
Posteriorly-
Anterior
border of
the trapezius
muscle
LevelVC
V. Grégoire et al., Radiotherapy and Oncology (2013)
Medially - Lateral edge of
sternocleidomastoid m,
lateral edge of level IVa.
Lateral Supraclavicular Group
Laterally –
Trapezius
and clavicle
Drains the posterior triangle
nodes (level Va and Vb)

48. Boundarie
s
Level VIa Level VIb
Cranial Caudal edge of the hyoid bone
or caudal edge of the
submandibular gland
Caudal edge of the thyroid
cartilage
Caudal Cranial edge of the sternal
manubrium
Cranial edge of the sternal
manubrium
Anterior Skin/platysma m. Posterior aspect of infrahyoid
(strap) m
Posterior Anterior aspect of the infrahyoid
(strap) m.
Anterior aspect of larynx, thyroid
gland and trachea
Lateral Anterior edges of B/L SCM m. Common carotid artery B/L
Medial - Lateral aspect of trachea &
esophagus
• Level VI – VIA (anterior jugular nodes) and VIB (pre-laryngeal,
pre-tracheal, para-tracheal-recurrent laryngeal nerve nodes)
• Drains the anterior floor of mouth, the tip of the tongue, the
lower lip, the thyroid gland, the glottic and subglottic larynx, the
hypopharynx, and the cervical esophagus
48

49. • Level VII – VIIA (retropharyngeal nodes) and VIIB (retro-styloid
nodes)
• Drains the mucosa of the nasopharynx, the Eustachian tube and
the soft palate.
49
Boundarie
s
Level VIIa Level VIIb
Cranial Upper edge of body of C1/hard
palate
Base of skull (jugular foramen)
Caudal Cranial edge of the body of the
hyoid bone
Caudal edge of the lateral process
of C1 (upper limit of level II)
Anterior Posterior edge of the superior or
middle pharyngeal constrictor m
Posterior edge of pre-styloid
para-pharyngeal space
Posterior Longus capitis m. and longus
colli m.
Vertebral body of C1, base of skull
Lateral Medial edge of the internal
carotid artery
Styloid process/deep parotid lobe
Medial A line parallel to the lateral edge
of the longus capitis muscle
Medial edge of the internal
carotid artery

50. • Level VIII - parotid node group : Drains frontal and temporal
skin, the eyelids, the conjunctiva, the auricle, the external
acoustic meatus, the tympanum, the nasal cavities, the root of
the nose, the nasopharynx, and the Eustachian tube
• Level IX – Bucco-facial group : Drains nose, eyelids, & cheek
Boundarie
s
Level VIII Level IX
Cranial Zygomatic arch, external
auditory canal
Caudal edge of the orbit
Caudal Angle of the mandible Caudal edge of the mandible
Anterior Posterior edge of mandidular
ramus (laterally) & medial
pterygoid muscle (medially)
SMAS layer in sub-cutaneous
tissue
Posterior Anterior edge of
sternocleidomastoid m.
(laterally), posterior
belly of digastric m. (medially)
Anterior edge of masseter m.
Lateral Superficial Muscular
Aponeurotic System (SMAS)
layer in sub-cutaneous tissue
SMAS layer in sub-cutaneous
tissue
Medial Styloid process Buccinator m.
50

51. • Level X – XA (retroauricular nodes) and XB (occipital nodes)
• Drains the posterior surface of the auricle, the external auditory
canal and the adjacent scalp
51
Boundarie
s
Level Xa Level Xb
Cranial Cranial edge of external auditory
canal
External occipital protuberance
Caudal Tip of the mastoid Cranial border of level V
Anterior Posterior edge of the external
auditory canal
Posterior edge of
sternocleidomastoid m
Posterior Posterior edge of
sternocleidomastoid m.
Anterior (lateral) edge of
trapezius m
Lateral Sub-cutaneous tissue Sub-cutaneous tissue
Medial Temporal Bone Splenius capitis m.

52. 52
V. Grégoire et al., Radiotherapy and Oncology (2013)
(superficial intraparotid)
(malar)
(buccal)
(facial)
superficial external
jugular(anterior jugular)
(preauricular)
(mastoid)
(submental)
(subauricular)

53. 53
(subparotid)
(transverse cervical A.)
(deep intra
parotid)
(Infrahyoid)
Mastoid
subauricular
spinal
accessory
nerve
(recurrent or paratracheal)
(prelaryngeal)
(pretracheal)

54. Head & Neck
• Anatomy With Lymphatic Drainage
• Etiology of Head And Neck Cancer
• Role Of HPV And EBV Virus
• Pathology & Prognostic Factors

55. Etiologyand RiskFactors
1. Tobacco & Alcohol - overexpression of bcl-2 and p53
mutations
2. Leukoplakia - White patch or plaque that cannot be
characterized clinically or pathologically as any other
disease.
3. Erythroplakia - Bright red velvety patch that cannot be
characterized clinically or pathologically as being caused by
any other condition
Hunter KD et al., Nature Reviews Cancer 2005
55

56. 1.
2.
3.
•
4. Oral Submucous Fibrosis
• Generalized fibrosis of the oral cavity tissues resulting in
marked rigidity and trismus.
5. HLA haplotypes, including A2, B46, and B17, are associated
with an increased risk of developing nasopharyngeal
carcinoma (Chan SH et al, Int J Cancer 1983).
6. High consumption of salted fish has been implicated as an
environmental factor in Southern China (Yu MC et al., Cancer
Res 1986)
7. UV radiation
8. HSV 1 & 2,EBV,HPV 16
9. Plummer Vinson syndrome
10. Occupational exposure: dust due to coal, iron, wood
Etiologyand RiskFactors
56

57. Head & Neck
• Anatomy With Lymphatic Drainage
• Etiology of Head And Neck Cancer
• Role Of HPV And EBV Virus
• Pathology & Prognostic Factors

58. • Human papillomavirus infects basal cells in the stratified
squamous epithelium.
• The 3 HPV oncogenes E5, E6, and E7 promote unrestrained
cellular proliferation to allow for viral amplification and also
contribute to the initiation and progression of cancer via the
same mechanism and by inducing genomic instability
• The standard test for HPV involvement in a tumor (and for
clinical trial enrollment) is detection of cyclin dependent kinase
inhibitor 2A (also known as p16) by Immunohistochemistry
• Particularly affects the palatine tonsils and tongue base;
associated poorly differentiated basaloid histopathology (Gillison
ML et al., 2004).
• Patients with HPV positive tumors, have improved survival after
chemoradiotherapy compared to patients with HPV-negative
tumors (Fakhry C et al., J Natl Cancer Inst 2008)
58
Role of HumanPapillomaVirus

59. 59
2) HPV E6, via activation of the ubiquitin ligase E6AP (E6 associated
protein), causes degradation of p53, leading to inhibition of
apoptosis
3) HPV E5 protein cooperates with E6
and E7 to promote proliferation in infected cells and is thought to
play a minor role in transformation
1) HPV E7 Protein degrades Rb protein
Degradation of Rb results in E2F transcription factors driving
expression of S phase genes, promoting progression through the
cell cycle
HPV
Blitzer GC et al., Int J Radiat Oncol Biol Phys 2014

60. • Several EBV genome products such as viral proteins, RNAs,
and miRNAs may participate in the development of NPC
(Raab-Traub, 2002).
• EBNA1, an EBV encoded nuclear antigen, promotes DNA
damage in NPC cells by reducing p53 levels and inducing
reactive oxygen species (ROS) (Raab-Traub, Seminars in Cancer
Biology 2002)
• Several studies have reported the upregulation of multiple
EBV-encoded miRNAs in NPC, but further studies are needed
to determine the exact role of BamHI fragment A rightward
transcript (BART) micro-RNAs in pathogenesis of NPC (Y Wang
et al, Eur J Cancer Prev. 2017) .
60
Role of Epstein-BarrVirus

61. 61
LMP1 further induces expression of the epidermal growth factor
receptor (EGFR), CD40, cell surface activation markers, adhesion
molecules, and anti-apoptotic factor
EBNA2 and EBNA-LP regulate expression of the latent membrane
proteins, LMP1 and LMP2
LMP1 interacts with the signaling adapter molecules of the tumor
necrosis factor receptor family
EBV
(Raab-Traub, Seminars in Cancer Biology 2002)

62. 62
(Raab-Traub, Seminars in Cancer Biology 2002)

63. Head & Neck
• Anatomy With Lymphatic Drainage
• Etiology of Head And Neck Cancer
• Role Of HPV And EBV Virus
• Pathology & Prognostic Factors

64. Pathology
• Aberrations in the p53 and Rb tumor suppressor pathways are
the most common molecular events, resulting in uncontrolled
cell proliferation.
• Other mutations include CDKN2A (Cyclin Dependent Kinase
Inhibitor 2A) , PTEN (Phosphatase and Tensin Homolog),
PIK3CA (PIK Catalytic Subunit Alpha) , and HRAS (human
proto-oncogene).
• Mutations in genes that regulate squamous differentiation,
such as NOTCH1 (translocation) , IRF6 (interferon regulatory
factor) , and TP63 - provided the rationale for testing novel
therapeutic targets such as NOTCH inhibitors
64
Stransky N et al., Science 2011

65. 65
Conformational change in the EGFR through dimerization, causing
subsequent auto-activation of the tyrosine kinase from the
intracellular domain of the receptor
intracellular signaling pathway leading to the inhibition of
apoptosis, activation of cell proliferation and angiogenesis, and an
increase in metastatic spread potential
The epidermal growth factor receptor (EGFR ) is overexpressed in
invasive HNSCC
Binding to EGFR by its natural ligands, mainly epidermal growth
factor or transforming growth factor α (TGF-α )
Pathology
Roskoski R Jr., Biochem Biophys Res Commun. 2004

66. 66
1. Factors related to Primary Tumor :
a) Tumor Dimension - Tumor Surface Diameter (pathologically
positive cervical LNs, local recurrence and survival); Tumor
Thickness (critical range 3-5 mm, risk of occult nodal
metastasis) & Tumor volume (local control).
b) Margin Status - Positive margin predict local recurrence
c) Malignancy Grading - Cellular Morphology & Host-tumor
interface (High Invasive Cell Grading Score associated with
presence of occult cervical metastases and extracapsular
extension )
d) Perineural Invasion - Involvement of vagal trunk,
glossopharyngeal and trigeminal nerves
e) Vascular Invasion - correlate with presence of cervical and
distant metastases
PrognosticFactors
Head and Neck Cancer: A Multidisciplinary Approach, 4th ed.
ICG includes degree of keratinization, nuclear polymorphism, number of mitoses,
pattern of invasion, stage of invasion, and lymphoplasmacytic infiltration

67. 1.
2. Factors related to the Cervical Lymph Nodes :
a) Number of Lymph Nodes
b) Extracapsular Extension
c) Node location - the presence of nodal metastases outside the
sentinel node region independently decreases 5-year survival
by more than 50%
3. Demographic Parameters : Alcohol and tobacco exposure
(response to radiotherapy, survival and risk of second primary
tumor of aerodigestive tract)
4. Patient’s General Medical Condition : Comorbidities
5. Molecular factors :
a) p53: Loss of function contribute to tumor aggressiveness by
promoting resistance to radiation & chemotherapy, accelerated
growth in hypoxic conditions, and tumor neovascularization.
b) VEGF expression correlate with local-regional recurrence,
distant metastasis, and poor survival.
c) EGFR overexpression correlate with radioresistance.
Head and Neck Cancer: A Multidisciplinary Approach, 4th ed.
67

68. 68
Thank You

69. Normalradiologicalanatomy–Larynxand
hypopharynxregion

70. Normalradiologicalanatomy–Larynxand
hypopharynxregion

71. Normalradiologicalanatomy–Larynxand
hypopharynxregion

72. Normalradiologicalanatomy–Larynxand
hypopharynxregion

73. Normalradiologicalanatomy–Larynxand
hypopharynxregion

74. Normalradiologicalanatomy–Larynxand
hypopharynxregion

75. Normalradiologicalanatomy–Larynxand
hypopharynxregion

76. Normalradiologicalanatomy–Larynxand
hypopharynxregion

77. Normalradiologicalanatomy–Larynxand
hypopharynxregion

78. 78
Indication Irradiation
Paranasal sinuses
Squamous carcinoma
Squamous carcinoma N+ and
undifferentiated carcinoma
Retropharyngeal nodes
Lateral pharyngeal nodes only
Levels I to V on the same side
Nasopharynx
Squamous cell carcinoma T1 – T4 N0
All undiferentiated carcinoma and
squamous carcinoma with node
involvement
Level II, retropharyngeal
and upper posterior triangle
Levels I to V
Nodal IrradiationBy TumorSite
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

79. 79
Indication Irradiation
Oral cavity
T2N0 with well-lateralized primary
T2N1 with well-lateralized primary
T2N0 with primary approaching
midline, all T3N0 and T4N0
All others
Levels I and II on the same side
Levels I to V on the same side
Levels I, II and III bilaterally
Levels I to V bilaterally
Oropharynx
T2N0 tonsil
T2N1 tonsil
T2N0 other sites
All others
Levels I and II on the same side
Levels I to V on the same side
Levels I, II and III bilaterally
Levels I to V bilaterally
Walter & Miller’s Textbook of Radiotherapy, 7th ed.

80. 80
Indication Irradiation
Larynx
T1–2N0 glottic
T3–4N0 glottic
T2N0 supraglottic
All others
No nodal irradiation
Levels II and III bilaterally
Levels II and III bilaterally
Levels I to V bilaterally
Hypopharynx
All Levels I to V bilaterally
Walter & Miller’s Textbook of Radiotherapy, 7th ed.