Carcinoma Oropharynx

1. MANAGEMENT OF OROPHARYNGEAL
CANCERS
Dr Kiran Kumar BR

2. • The oropharynx is the
portion of the
continuity of the
pharynx extending
from the plane of the
superior surface of
the soft palate to the
superior surface of
the hyoid bone
(or vallecula).

3. Oropharynx
 Base of the tongue,
Vallecula,
 The inferior (anterior)
surface of the soft
palate
 The uvula,
 The anterior and
posterior tonsillar
pillars,
 The glossotonsillar
sulci,
 The pharyngeal tonsils,
and
 The lateral and
posterior pharyngeal
walls.

4. Lymphatic Drainage
 Levels II, III, and IV most common
 Retropharyngeal
 Posterior pharyngeal wall
 Palatine tonsil
 Bilateral drainage
 Tongue base
 Soft palate
 Posterior pharyngeal wall
 The probability of lymphatic
metastasis is related to the size
and location of the primary tumor
within the oropharynx.

5. DISTRIBUTION OF CLINICAL METASTATIC NECK NODES
FROM HEAD AND NECK SQUAMOUS CELL CARCINOMAS

6. Epidemiology
 Account for approximately 10-12% of head and
neck malignancies worldwide.
 Incidence is high in developing countries 4.8 in
100,000.
 There is increase in HPV associated oropharyngeal
cancers.
 Peak incidence in 6th or 7th decades oflife.
 More common in men(4:1).

7. Risk Factors
Patient related-
Age and gender: predisposition in males especially
those who are smokers and older than 50 years.
Lifestyle: cigarette smoking, alcohol, tobacco; tobacco
and alcohol are synergistic risk factors.

8. HPV- associated orpharyngeal cancer
• HPV is a circular double stranded DNAvirus
• Found to be associated with cervical cancer in 1983.
• Appr. 150 types of HPV have been identified
• HPV 16 is most common type asso. with more than 90% of all
oropharyngeal cancers.

9. HPV structure
• HPV genome encodes 3
oncoproteins(E5,E6,E7),regula
tory genes(E1,E2),capsid
proteins(L1,L2).
• Oncogenesis is primarily
mediated via the E6 and E7
proteins. HPV E6 complexes
promote ubiquitin-mediated
destruction of p53.
• Loss of cellular p53 function
results in dysregulation of the
G1/S and G2/M checkpoints.
• E7 is believed to be the major
transforming oncogene during
early carcinogenesis, with E6
functioning later.

11. Clinical characteristics-HPV associated
• more likely to occur among men than women (3:1)
• most of whom (80%) will not have a smoking history.
• diagnosed in individuals who are 5 to 10 years younger than HPV-
unassociated oropharyngeal cancers
• p16 IHC testing is an accurate surrogate for HPV infection

12. Response of HPV associated cancers
• Patients with HPV-associated oropharyngeal cancers have
significantly better outcomes compared to HPV-unassociated
oropharyngeal tumors.
• In RTOG 0129, HPV status was independently associated with
improved outcomes. Three-year overall survival was 82% in HPV-
positive patients compared with 54% in HPV-negative patients

14. Pathology
• Squamous cell carcinoma (SCC) accounts for >90% of
oropharyngeal cancer
• Minor salivary gland carcinomas
• Lymphoma
• Plasmacytoma
• Sarcoma
• Melanoma

15. Route of spread
Local
Oropharynx cancers may invade
vallecula/larynx,
 parapharyngeal area into the pterygoid muscles/plates,
nasopharynx, and oral cavity (oral tongue and retromolar
trigone)
Perineural invasion especially along branches of CN V and VII

16. Lymph node involvement is seen in 55% of oropharynx
cancers.
• most common location for lymph node metastases from
oropharyngeal cancers is the ipsilateral level II.
• The typical order of metastatic progression is systematic,
from the upper jugular chain nodes superiorly (level I/II; first
echelon), to mid-cervical (level III), and to lower cervical
nodes (level IV), inferiorly. Retropharyngeal nodes represent
a nodal drainage for oropharynx cancers.
• Contralateral nodes are at risk for tumors near midline,
advanced T- and N-stage diseases

17. Distant Metastasis in patients with advanced-stage disease
• The most common site of hematogenous metastasis is Lung.
• Seen in about 20% cases.
• However, a primary lung cancer should always be excluded.

18. Clinical Features
 Asymptomatic neck node
 Pain
 Dysphagia
 Otalgia
 Foreign body sensation
 Hemoptysis
 Weight loss

19. Otalgia

20.  T, tumor
 N, node
 M, metastasis
OropharyngealCancer
Staging
 Tx: primary site cannot be evaluated
 T0: no evidence of carcinoma
 Tis: carcinoma in-situ
 T1: tumor < 2cm in greatestdimension
 T2: tumor 2-4cm in greatestdimension
 T3: tumor > 4cm in greatestdimension
 T4
 T4a: invades larynx, deep/extrinsic tongue
muscles, medial pterygoid, hard palate, or
mandible
 T4b: invades lateral pterygoid, pterygoid plates,
lateral nasopharynx, skull base, or carotid

21.  T, tumor
 N, node
 M, metastasis
Invasion of pre-epiglottic fat
(i.e. laryngeal involvement)
Invasion of medial
pterygoid muscle
 T4a: invades larynx, deep/extrinsic tongue muscles, medial
pterygoid, hard palate, or mandible
 T4b: invades lateral pterygoid, pterygoid plates, lateral
nasopharynx, skull base, or carotid

22.  T4
 T4a: invades larynx, deep/extrinsic tongue muscles, medial
pterygoid, hard palate, or mandible
 T4b: invades lateral pterygoid, pterygoid plates, lateral
nasopharynx, skull base, or carotid
Encasement of
carotid artery
Involvement of
foramen ovale

23.  T, tumor
 N, node
 M, metastasis
Staging
 Nx: Regionallymph nodes cannotbe assessed
 N0: No regional lymph nodemetastasis
 N1: single ipsilateral node <3cm
 N2
 N2a: single ipsilateral node involved, ˃3but
• ˂6cm
 N2b: multiple ipsilateral nodes, < 6cm
 N2c: bilateral or contralateral nodal involvement, none ˃6cm
 N3: nodal involvement >6cm

24.  T, tumor
 N, node
 M, metastasis
Staging
 Mx: distant metastasis cannot be
evaluated
 M0: no distant metastasis
 M1: distant metastasis present

25. Diagnostic workup
• Complete physical examination-examination of oral cavity,
oropharynx, neck.
•Mirror examination
• Endoscopic Examination
 Fiberoptic laryngoscopy is done to assess local extent of
dosease.
 Evaluation of the upper aerodigestive tract is crucial to
evaluate the primary site of disease and the presence of
synchronous primaries.

26. Laboratory
tests
Includes:
1) Complete blood count
2) Basic blood chemistry
3) Hepatic and metabolic panels
4) Testing for HPV in the biopsy specimen (p16 IHC testing)

27.  Biopsy
 Tissue from either primary tumor or neck lymphadenopathy
is crucial for pathologic diagnosis.
Imaging-
 CECT Face & Neck
 Chest X-ray
 Ultrasound whole abdomen
 CECT Thorax (if indicated)
 FDG-PET/CT scan

28. CT Scan
• Scan slice thickness <5 mm is desirable to optimize the
detection of smaller pathologically involved lymph nodes.
• Pathologically involved lymph nodes are characterized on
CT imaging as those that are enlarged, enhance with
contrast, and have a necrotic centre.
• Primary tumors appear as contrast-enhancing masses,
distorting normal anatomic relationships.
• Whereas ulceration and invasion into surrounding organs
are readily assessed, submucosal spread is often difficult to
characterize with CT.
• Thoracic CT should be performed routinely to assess for
pulmonary spread of oropharyngeal cancer patients with N2
or greater nodal disease, as well as those with advanced
primary tumors due to risk of pulmonary metastases.

29. Magnetic ResonanceImaging
• Magnetic resonanceimaging (MRI) canbe auseful imaging tool for
oropharyngeal tumors.
• Squamous cell carcinoma appears aslow signal in T1MRI and
corresponding high signal in T2sequences.
• Theability of MRI to differentiate tumor from soft tissues is
particularly useful when determination of the extent of base of
tongue or oral tongue invasion isneeded.
• Additionally, MRI is useful in patients with compromised renal
function who are not able to receive iodine-based CTcontrastagents.

30. PositronEmissionTomography
• Positron emission tomography (PET) and/or PET/CT
imaging incorporating tumor physiology in conjunction with
anatomic information are now routinely recommended for
the initial staging of oropharyngeal cancer patients.
• PET-based imaging can assess not only the locoregional
burden of disease but also detect and quantify distant
metastases.
• It has high sensitivity approaching 100%, and about 60%
specificity.
• As per NCCN guidelines FDG-PET/CT should generally
considered in Stage III-IV disease.

31. Treatment
modalities
• Surgery
• Radiotherapy
• Chemotherapy
• Targeted Therapy

32. • Stage I and stage II tumors are considered as early stage,
whereas stage III and IV (nonmetastatic) are considered
locoregionally advanced disease.
• Early-stage tumors are usually well controlled with a single
local modality, either radiotherapy or surgery.
• For locoregionally advanced disease, two appropriate
treatment strategies are used:
(a) either surgery followed by radiation therapy with or
without chemotherapy based on pathologic risk factors or (b)
radiotherapy usually given with chemotherapy.

33. Surgery
• Base of Tongue
• Surgery plays a limited role in the management of base of
tongue tumors given the inherent morbidity of a near-total or
total glossectomy, which is required for large and/or midline
tumors.
• For select, well-lateralized base of tongue tumors with
minimal cervical lymphadenopathy, a partial glossectomy
can be performed.
• Given the high propensity for occult microscopic nodal
involvement, bilateral cervical lymph node dissection is often
performed.
• Base of tongue tumors in close proximity to the laryngeal
apparatus, such as those arising in the vallecula, often
require a supraglottic or total laryngectomy to achieve
adequate margins of resection.

34. • Traditional surgical approaches for base of tongue tumors
include :
• The midline mandibulotomy (splitting the lip, mandible, and
oral tongue midline),
• The lateral mandibulotomy (dividing the mandible near the
angle and approaching the base of tongue from the side),
• The floor drop procedure (elevating the inner periosteum
from the mandible from angle to angle, which releases the
entire floor of mouth and oral tongue into the neck, exposing
the base of tongue).

35. TonsilCancers
• For small (<1 cm) early-stage tonsil cancers confined to the anterior
pillar, a wide local excision can achieve adequate tumor-free margins,
whereas tumors involving the palatine tonsil often require a radical
tonsillectomy.
• For both of these situations, the tonsil is approached transorally, with
primary closure.
• Larger tumors with extension onto the tongue, onto the mandible or
into surrounding tissue often require a composite resection, usually
including resection of the tonsil, tonsillar fossa, pillars, a portion of the
soft palate, tongue, and mandible.
• For tumors not adjacent or adherent to the mandible, a midline
mandibulotomy approach is used.
• For tumors adherent to the mandible, a partial mandibulectomy is
used.
• Complications from surgery depend on the extent of resection, with
impairment in swallowing possible by removal of part of the tongue or
soft palate.

36. SoftPalateCancers
• Surgical resection is rarely recommended as initial therapy
for soft palate tumors.
• Resection of the soft palate is often associated with
significant reflux into the nasopharynx during swallowing,
even with the use of custom prostheses.
• Additionally, because of the midline location, primary
disease spreads bilaterally to the neck with frequency high
enough to require elective treatment.
• However, when surgery is performed, the tumors are
approached transorally and a full-thickness wide local
resection is performed for tumors limited to the soft palate.
• A more extensive composite resection is required if disease
extends to surrounding structures.
• Flaps or prostheses are used to preserve velopharyngeal
competence. Nasal speech is also often a consequence.

37. TransoralLaserSurgery
• Small series report favorable outcomes for selected patients
with stage I through stage IV oropharyngeal tumors treated
with transoral laser microsurgery with or without neck
dissection, followed by adjuvant radiotherapy or
chemoradiotherapy.
• Positive margin rates are variable (3% to 24%) and appear
to vary based on primary site, being more common in base
of tongue tumors.
• Complications include postoperative hemorrhage (5% to
10%).
Temporary tracheostomy placement is relatively common
(17% to 30%) and needed for exposure, airway control, or
aspiration following extensive resection.
• High rates of locoregional control following this procedure
have been reported, primarily for stage I/II patients (87% to
100%), although for stage III/IV patients, local recurrence is
more common (20% to 30%).

38. TransoralRoboticSurgery
• The most common robotic surgical system, the da Vinci Surgical
System, is comprised of three surgical instruments and a binocular
endoscope controlled by robotic arms and inserted under direct or
endoscopic guidance by the surgeon from a patient-side apparatus.
• The operative environment is visualized virtually, in a three-
dimensional (3D) environment created via a computer that links the
environment provided by the binocular endoscope to the position of
the instruments.
• The surgeon’s movements are translated into the micromovements
of the instruments. The advantages of this system include motion
scaling, which can increase precision as well as reduce hand tremor
and fatigue.
• When the system is used for transoral surgeries, an assistant is
often positioned by the patient’s head.

39. • There are no prospective randomized studies supporting the
use of transoral robotic surgery (TORS) for oropharyngeal
tumor resection over conventional surgery.
• Until mature prospective multi-institutional series and
randomized data are available, the true utility of transoral
laser microsurgery and TORS remains unknown.
• Although early results are favorable and associated with
shorter hospital stays, long-term data are needed.
• Additionally, standard oncologic principles limiting the
number of modalities used to minimize treatment related
side effects should be carefully considered prior to
widespread adoption of the surgical techniques.

40. Neck Management
• The type of neck dissection (comprehensive or selective) is
defined according to preoperative clinical staging, is
determined at the discretion of the surgeon, and is based on
the initial preoperative staging as follows:
N0= Selective neck dissection, atleast Levels II-IV
N1-N2a-c= comprehensive neck dissection
N3= Comprehensive neck dissection

41. Radiotherapy
• Definitive chemoradiotherapy is the treatment of choice.
• For early-stage oropharyngeal cancers, the use of radiation
therapy as a single modality is associated with good
outcomes and functional preservation.
• Patients with locoregionally advanced oropharyngeal cancer,
concurrent chemoradiotherapy is the standard treatment.
Resection is generally not recommended given the
associated surgical morbidity.

42. Chemotherapy
• Used in concurrent setting along with radiotherapy
• Recurrent and metastatic tumors
• As neoadjuvant chemotherapy, but there is no definitive role.

43. Radiotherapy
techniques
• Two dimensional planning
• 3D planning
• IMRT

44. Conventionalborders

46. CarcinomaBaseoftonguelower
NeckField

47. 3DPlanning
• Patients should undergo simulation, preferably CT based, to
allow for optimal radiotherapy planning.
• A peripheral IV should be placed prior to simulation for the
delivery of low osmolar iodinated contrast to optimize the
distinction between vascular structures and lymph nodes.
• Patients are positioned supine, extended head position is
preferable.
• Care should be taken to ensure that the mask is tight and
should not allow movement of the nose, chin or, forehead.

50. Chemotherapy

52. RoleofTargetedTherapy
• EGFR inhibitors have been tried in H&N cancers
• Weekly Cetuximab loading doseof 400 mg/m2 followed by 250
mg/m2 for locoregionally advanced head and neck cancer patients
• Thecombination therapy wasfound to improve locoregional
control, disease-free survival, and overall survival

53. CETUXIMAB IN HPV+ OPC

54. Follow up
• Every 1 to 3 months for the first year post RT
• Every 2 to 4 months in the second year post RT, and every 4
to 6 months in the next 3 to 5 years.
• The intensity of the examinations within the first 2 years
coincides with the likelihood of recurrence in the interval.
Given that radiation to the neck commonly causes
hypothyroidism, thyroid-stimulating hormone levels should
be evaluated every 6 months.
• Follow-up imaging should be performed within the first 3
months of treatment

55. ReirradiationforLocoregionallyConfinedRecurrentorSecond Primary
Disease
• Surgical resection is recommended, although this is possible
only in a small proportion of patients.
• Following surgery in those with high-risk pathologic features
or in those who are not surgical candidates,a second course
of full-dose radiotherapy with chemotherapy has been
shown to result in long-term survival in approximately 20% of
patients.

56. THANKYOU