MANAGEMENT OF OROPHARYNGEAL CANCER
Prof. Dr. Ismail Zohdi
Surgical Anatomy
The oropharynx occupies the
area of the aerodigestive tract
between
• oral cavity
• nasopharynx
• & hypopharynx
Surgical Anatomy
Oropharynx extends :
From hard palate superiorly
hyoid bone inferiorly
Surgical Anatomy
Oropharynx includes:
• Tonsillar fossa
• Base of the tongue
• Soft palate
• Pharyngeal wall
Surgical Anatomy
Anterior wall:
• Base of tongue
• Vallecula
• Lingual surface of epiglottis
• Pharyngoepiglottic fold
Surgical Anatomy
Lateral wall:
• Tonsil
• Anterior pillar
• Posterior pillar
Surgical Anatomy
Roof:
• Soft palate containing:
- 2 heads of palatopharyngeus
- levator palati
- tensor palati
- palatoglossus
Surgical Anatomy
Posterior wall:
• Vertebrae of C2&3
• Superior constrictor m.
• Middle constrictor m.
• Buccopharyngeal fascia
Surgical Anatomy
Surgical Anatomy
• Irregular surfaces of T&TB difficult to detect small tumours
• IX&X cause referred pain to the ear
• RPS&PPS potential routes for cancer spread
• Lack of natural bounderies surgical margins difficult to achieve
• Tumours of T&P invade or encase bone (mandible & maxilla)
• Muscle involvement trismus & pain
• TB tumours larynx, tonsil & oral tongue
Functions
Oropharynx plays a role in:
• Respiration
• Swallowing
• Speech
Functions
Extirpative surgery of OP may result in:
• Poor speech production
• Dysphagia
• Aspiration
As a result of::
• Velopharyngeal incompetance
• Pharyngeal stenosis
• Inappropriate functioning of TB
• Decreased pharyngeal contraction
• Sensory denervation
• Delayed triggering pharyngeal swallow
Oropharyngeal Malignancies
Saliv 2%
Lymphoma 8%
SCC
Lymphoma
Saliv
SCC 90%
Squamous Cell Carcinoma
soft
palat
e Post wall 5%
10%
lat
TB
TB 25%
soft palate
lat 60% Post wall
Incidence
• Relatively uncommon
• < 1% of all new cancers
• >55-65 years of age
• Male predominance
Aetiological Factors
• Smoking (>10 packs years)
• Heavy alcohol use
• HPV-16 (number of oropharyngeal cancers linked to HPV infection is increasing,
E6,E7 oncoprotein lead to malignamt transformation )
• Other risk factors include:
- diet low in fruits & vegetables.
- drinking yerba maté (stimulant drink common in South America)
- chewing betel quid ( mild stimulant used in Asia)
- exposure to polycyclic aromatic hydrocarbons,
asbestos & welding fumes
Demography
• Younger adults
• Increased incidence among women
• Nonsmokers
• Orogenital sex
• Well-differentiated tumours
– Decrease in incidence
– Five-year survival rates improved by 15%
• Poorly-differentiated tumours
– Increase in incidence
– Five-year survival rates improved by > 50%
HPV
• Predominantly poorly differentiated SCCA
• No increase in lymphovascular or perineural invasion
• Highly predictive of lymph node metastasis
What is new?
• SCC • Management
– Increased – CRT
– Non-smoker – HPV more sensetive
– HPV – Trans-oral
– Younger
Management
ge ry.
sur
ical
80 Rad
.
90 CRT
l.
20 Tran
so ra
?? Immun o
.
Feature HPV -ve HPV +ve
Incidence Decreasing Increasing
Risk factors Tobacco, alc Sexual behavior
Age >60 <60
Field cancer Yes No
Prediliction site None Orophx
T stage Higher Lower
N stage Lower Higher
Prognosis Poor Favorable
Why HPV id
HPV +ve has better prognosis
De-escalating
Better Survival Treatment
Regimens
Long-term morbidity associated
with current treatment will be
longer lasting
De-escalating Treatment Intensity
• Potential to reduce • De-escalating Strategies
– Gastric tube dependence – Cetuximab [alternative
to Cisplatin given
– Osteoradionecrosis
concurrently with RTH]
– Dysphagia – RTH dose when
– Xerostomia combines with chemo as
1ry treatment
– Dental decay – adjuvant chemo or
– Hypothyroidism radio dose following 1ry
surgery
– Carotid stenosis
Conclusion
• HPV +ve tumour is important prognostic marker in
oropharyngeal carcinoma
• HPV detection should be considered:
– middle-aged group,
– low tumour stage with high nodal status
• p16-IHC is the most practical method to determine HPV
status
• +ve-HPV status is prognostic factor of better survival
Neck
• Levels II-III-IV (55%-33%-20%)
• 50% +ve [clinical or radiological]
• 30% of cN0 are +ve pathological
• Retroph
– Post>soft>tonsil>TB
– Not the primary echelon nodes
– Occur when the lymphatics are disrupted in
the case of node positive disease in the
jugulodigastric nodes or in the case of prior
treatment with either surgery or radiation
Neck
• Contralateral
– Soft>TB>post
– Tonsil 10%
• Cystic (branchial cleft carcinoma)
• Initial presenting sign
Distant Metastasis
Differs from H&N
• 8% at presentation
• Rich lymphatics
• 15-20% at some stage 80% within 2 years
• > with LN metastasis & recurrence
• Lung,bones, liver
Second Primary
• One in three develop 2nd primary at some time
• Consider synchronous 2nd primary
• > if with contralateral LN
Presentation
• Symptoms of 1ry disease with/without LN metastasis
• LN metastasis with clinically detected OPSCC 1ry
• LN metastasis with unknown 1ry
Symptoms
• Sore throat that does not go away
• Dysphagia
• Trismus
• Trouble moving the tongue
• Otalgia
• A lump in the back of the mouth, throat, or neck
• Change of voice
• Haemoptysis
• Weight loss for no known reason
Clinical Examination
• Head & neck examination
• Base of tongue palpation (submucosal
disease or a strong gag reflex may make palpation
more difficult)
• Flexible fiberoptic laryngoscopy
Lateral Wall Tumours
• Originate at one or more sites within deep
nests of tonsil
• Grow entirely beneath the surface
• Increase in the size of the tonsil
• Increased firmness of the area.
• Exophytic fungating mass with central
ulceration & heaped-up edges (deep red to
white)
Lateral Wall Tumours
Spread:
• Ant. & upwards retromolar trigone,TB
• Anterolateral angle of mandible
• Posterolateral parapharyngeal space
(carotid art.or superior extension skull base)
• Inferiorly lat pharyngeal wall PF
• Deep pterygoid m.(trismus & pain)
Tongue Base Tumours
Symptoms:
• Often submucosal (detected by palpation)
• Sensation of a mass in the throat
• Mass in the neck
• Referred ear pain or hemoptysis
• Advanced stages appear clinically
Tongue BaseTumours
Spread:
• Cross midline
• Anteriorly oral tongue, floor of mouth
• Inferior & posteriorly vallecula, epiglottis
• Deep genioglossus m.& styloglossus m.
Soft PalateTumours
Symptoms:
• Asymptomatic in the very early stages
• Often found at early stages incidentally
by the patient or the physician
• Ulcerative surface lesions
• Palate mass, bleeding, + foul odour
• Pain in advanced stages
• Velopharyngeal insufficiency
• Altered speech
• Difficult swallowing
• Referred otalgia
• Trismus
• Neck mass (>bilateral)
Soft PalateTumours
Spread:
• Superior pole of tonsils
• Retromolar trigone
• Inferior or superior alveolar process
• Hard palate
• Base of tongue.
Soft PalateTumours
Spread:
• Extension sphenopalatine
foramen may result in palatal
hypostasis
• Extending nasopharynx (middle ear
effusion is common)
• Extend anterosuperiorly pterygo-
palatine & infratemporal fossa
Posterior Wall Tumours
Symptoms:
• Usually late
• Dysphagia
• Sore throat
• Otalgia
Posterior Wall Tumours
Spread:
• Submucosal nasopharyngeal & hypopharyngeal wall
• Prevertebral fascia barrier to spread
Investigations
Laboratory Studies:
• CBC
• Serum alkaline phosphatase
• Liver function test
• HPV testing
• Pulmonary function testing, arterial blood gas
Investigations
HPV testing:
• NCCN (National Comprehensive Cancer Network) guidelines
recommend HPV testing for prognostic factors
• Quantitative reverse transcriptase PCR (QRT-PCR) allows
calculation of relative amounts of mRNA present in the sample
– Able to calculate copy number
– Susceptible to false positives
• Type-specific HPV DNA in situ hybridization
– HPV-16 is most commonly used to examine oropharyngeal carcinomas.
– It is both sensitive and specific.
• P16 can be tested as a biomarker for HPV E7 activity
Investigations
Imaging:
• CT scanning with intravenous contrast (standard imaging technique )
• MRI (offers the advantages of finer tissue detail and multiplanar views)
• PET-CT
• Ba swallow, fluoroscopy
• Chest X-ray, scan (2nd primary, metastasis)
• U/S liver
Biopsy
The following may be contraindications to
biopsy, or they may alter the circumstances
of the biopsy (office vs operating room):
• Bleeding diathesis
• Airway issues that could be exacerbated by
the biopsy
• Lesion located near vital structures that could
be injured by biopsy
Biopsy
• Systematic panendoscopy
- definitive histology
- accurate staging
- exclude 2nd primary
- assess surgical resectability
• Incisional [?tonsillectomy]
• Deep biopsy for base of tongue
• FNAC of LN (+/- ultrasound guided)
Staging
N0 N1 N2-3
T1
I
T2 II
T3
III
T4
IV
Staging
N0 N1 N2-3
T1 I
T2 II
T3
III
T4
IV
Staging (Lymphoma)
Management
Multidisciplinary approach:
• H&N surgical team
• Medical oncology
• Radiation oncology
• Dental team
• Nutritionist
• Speech and swallow
• Social work
Management
Treatment options depend on:
• Stage of the cancer.
• Keeping the patient's ability to speak
and swallow as normal as possible.
• Patient's general health
Management
• Is the primary tumour resectable?
• Is the neck disease resectable?
• Is there distant metastatic disease?
• What is the expected functional outcome following
surgery?
• Are there comorbid patient conditions that will affect
surgical outcomes?
• What is the patient’s preference for treatment?
Management
The prognosis depends on:
• Stage of the cancer.
• Number and size of lymph nodes
• HPV infection of the oropharynx
• History of smoking for > ten pack years
Management
Contraindications to surgery include:
• Medical conditions precluding a general anesthetic
• Patient declines surgical treatment
• Carotid artery encasement
• Paraspinous muscle invasion
• Vertebral column invasion
• Skull base invasion
• Lateral pterygoid muscle invasion
• Pterygoid plate invasion
• Unresectable neck disease
• Distant metastatic disease
Management
•Treat both necks for central lesions
• Primary tumour •Address retropharyngeal nodes
•Occult lymph node metastasis up to 35%
– T1 and T2: surgery or RT
– T3 and T4
• CRT ( severe functional impairement , post OP , >1/2 BT,
oral T, PPS,PVF,CA)
• Surgery with postoperative RT (HPV-ve, mandibular invasion)
• Neck
– N0 and N1: surgery or RT
– N2 and N3
• Surgery with post-op RT
• CRT and planned neck dissection
Management
• High rate of clinically +ve and occult nodal metastasis
• Retropharyngeal nodes
- pre-operative imaging
- posterior pharyngeal wall invasion
- >N2
- contralateral nodal metastasis
- ipsilateral multilevel involvement
• Less predictable lymphatic pathways
• RT (even when 1ry is treated surgically)
Early stage I and II
• Same
• Single modality (RT vs. surgical) • RTH
• Less morbidity
• Surgical treatment • LN
– Transoral robotic surgery/transoral laser surgery—
improved exposure with minimally invasive
technique
• Comparable oncologic outcomes for T1 and T2
• Potential for de-escalation adjuvant RT and chemo
(under investigation)
– ± SND
Early stage I and II
– Indications for postoperative RT:
• N0 ( 2 ormore +ve nodes, ECS)
• N2-3
• T>2
• Close resection margins
• PNI
– Indications for postoperative CRT :
• Positive resection margins
• Extracapsular spread in the lymph nodes
Advanced stage III and IV
Multimodality:
– Surgery followed by RT alone or + CT
– RT alone for patients who cannot have CT
– RT + targeted therapy
– CRT
– A clinical trial of CT followed by RT
– A clinical trial of transoral robotic surgery
followed by RT or CRT
Advanced stage III and IV
• Surgical approaches:
Transoral ( good visualization,no external incisions, hindered by
teeth, height of mandible &trismus, tongue size,tori,flexibility of the
neck, prior radiation & tumour exrent):
– Davis mouth gag, Feyh-Kastenbauer system
– Ensure good visualization (1-2 cm perimeter)
– Small , superficial
– Upper, anterior sites
– Evaluate extent & mobility of tumour
– Transoral resection tonsil carcinoma
approaches the anatomy from “inside-out”
– Ligate posterior lingual branches & ascending
pharyngeal art.or use of surgical hemoclips
Advanced stage III and IV
Transoral microsurgery + CO2 laser:
– More precise
– Enhanced visualization by the microscope
– Lateral wall, post.wall ,TB & vallecula
– Remove the tumor piecemeal
– Communicate effectively with the pathologist
– Good local control & functional results
– Minimal morbidity
Advanced stage III and IV
Transoral robotic surgery:
– 3-D visualization
– Wristed instruments,
– 3-D mobile instruments
– Angled endoscopes
– Robotic surgeon & manual assistant
work simultaneously
– Tremor filtration
Advanced stage III and IV
– Single modality(>early stages) or de-
intensification of adjuvent CRT
– Better functional result
– By staging patients with TORS and neck
dissection, adjuvant therapy can be
tailored to the individual patient and can
be deintensified
Advanced stage III and IV
Mandibular lingual release:
– More in TB
– Less access to lateral pharyngeal wall & PPS
– Lingual arteries & nerves, XII are at risk
– No mandibulotomy or lower lip split required
Advanced stage III and IV
Transcervical transpharyngeal approaches:
• Suprahyoid approach—access to midline TB:
- entered through vallecula
- < visualization of superior margin
- risk cutting through tumour
Advanced stage III and IV
• Lateral pharyngotomy approach:
- poor exposure of superior lesions of tonsillar fossa
or RMT region
- > small lesions of BT & pharyngeal wall
- entered posterior to thyroid ala
- superior laryngeal nerve & XII at risk
Advanced stage III and IV
Transmandibular approaches:
• Midline labiomandibular glossotomy:
- rarely used
- incision can be carried hyoid bone
- bleeding & neurological deficits are minimal
- no access to PPS or lateral oropharynx
Advanced stage III and IV
• Mandibular swing approach:
- wide exposure to entire OP & PPS
- en bloc resection of tumour & LN
- mandibulotomy anterior to mental nerve
- soft tissue cut floor of mouth
- destract mandibular segment & tongue
Advanced stage III and IV
• Mandibulectomy:
- oropharyngeal composite resection with mandibulectomy
- used in advanced cancers with bony invasion
- mandibular cut well clear of the tumour
- disadvantage resultant functional & cosmetic deficits
- reconstruction free tissue transfer (osteocutaneous flap)
Advanced stage III and IV
Reconstructive methods:
Provide wound closure, functional stability, and
cosmesis, introduce healthy tissue in a previously
irradiated bed:
• Oral prosthetic
• Healing by secondary intention
( fibrosis ,re-epithelization)
• Primary closure (water tight,no tension)
• Split-thickness skin graft
Advanced stage III and IV
• Mandibular reconstruction
- no bony reconstruction
- free bone graft
- costochondral graft
- serratus muscle/rib myo-osseous flap
- pectoralis major with rib
- fibula flap
- deep circumflex iliac artery flap
- composite radial flap
• Locoregional flaps:
- sternomastoid myofacial flap
- lingual flap
- temporalis flap
- buccal mucosal transposition flap
Advanced stage III and IV
• Myocutaneous pedicle flaps:
- not ideal
- limits of arc of rotation
- pulled inferiorly by its weight
Advanced stage III and IV
• Microvascular free flaps:
- radial artery f.f. (flap of choice, pliable)
- anterolateral thigh f.f. ( in thin patients,
<donor site morbidity, increased bulk)
- designed three dimensional
- slightly reduced size
- not too tight or overly constricted
Advanced stage III and IV
• Radiotherapy :
– 6-7 week course , dose 60-70 Gy
– Using intensity-modulated radiation therapy (IMRT)
– Techniques include electron boost, brachytherapy,
hyperfrationation
– PET/CT evaluation after 8-12 weeks
– Indications:
• Primary single modality
• Adjuvant treatment
• Patients with surgical
• Advanced-stage tumours
• Unresectable tumours
Advanced stage III and IV
• Chemotherapy :
- Associated with improved overall survival
in advanced OPSCCA
– Given concurrently with RT
– A clinical trial of CT followed by RT
– Primary chemotherapy reserved for palliation
without curative intent
Cetuximab (ERBITUX ®)
• EGFR [Epidermal growth factor receptor] inhibitor
• Monoclonal antibody (type of targeted therapy )
• Antibodies can identify substances that may help
cancer cells grow
• Attach to these substances and kill the cancer cells,
block their growth, or keep them from spreading
• IV infusion • Activation autophosphorylation
• Overexpression
• Resistance (HER2/neu protein)
• Acne like rash constant activation
uncontrolled cell division
• 30% of all epithelial cancers.
Advanced stage III and IV
• Treatment of cervical nodal disease :
– N0 neck managed with regional radiotherapy or planned
neck dissection dictated by tt of the primary tumour (> RT
retropharyngeal LN)
– Both necks treated if there is clinical disease in one side
– Consider post-RT surgical salvage for bulky nodal disease
– Consider post- surgical RT for the presence of ECS
Advanced stage III and IV
– Neck nodes N2-3 treated by CRT :
if posttreatment PET/CT is +ve neck dissection
if PET/CT is –ve watchful waiting approach
Advanced stage III and IV
• Palliation:
– Metastatic or unresectable disease
– Involve RT, CT, or both
– Tracheostomy, PEG if indicated
– Consider tumour debulking, radio-frequency
ablation for large painful ulcerative lesions
Follow UP
• Close observation
1rst year 1-3 m
2nd year 2-4m
3rd year 3-6 m
4th&5th year 4-6 m
>5 years yearly
• Lifelong follow-up (2nd primary)
• Serial PET/CT evaluation (beginning 8-12 weeks after
completion of therapy)
Prognosis
5-year survival:
• Stage I 67%
• Stage II 46%
• Stage III 31%
• Stage IV 32%
Future and Controversies
• ?? OPSCC to be treated primarily with surgery or with
organ-preservation chemoradiation.
• Each treatment has its own risks
• Decision has to be made in conjunction with the
recommendations of the multidisciplinary team and the
preferences of the patient.
• Minimally invasive techniques offer patients an excellent
option for treatment both from a functional and an
oncologic standpoint.
Future and Controversies
• Antibodies against the HPV may
help identify individuals at
increased risk of HPV related
OPSCC
• When present, they were detectable
many years before the onset of
disease.
• This raises the possibility that
a blood test might one day be used
to identify patients with OPSCC
