Introduction
Th e incidence of oropharyngeal carcinoma (OPC) in the UK doubled over the last decade to 2.3 per 100,000 (National Cancer Intelligence Network, 2010 ), mostly attributed to human papillomavirus (HPV) infection and aff ecting younger patients, while the incidence related to smoking and drinking is decreasing and aff ects older patients.
Current HPV prevalence in OPC in the West is reported to be as high as 72% (Mehanna et al. , 2013 ), with HPV 16 being the predominant subtype. Th e most common subsites are the tonsil and tongue base. HPV-positive patients typically present with early T stage and more advanced N stage with lymph nodes that are oft en cystic in nature.
Anatomy
Th e oropharynx extends from the palate to the hyoid. Th e boundaries are:
• superior – the junction of the hard and soft palate; • inferior – the vallecula/hyoid;
• anterior – the circumvallate papillae; • posterior – the posterior pharyngeal wall; • lateral – the lateral pharyngeal wall. are at risk and are included in the treatment volume
in virtually all patients. Th e practice varies across dif- ferent centres regarding clinical target volume (CTV) delineation, dose prescription, dose constraints and acceptance criteria. Most centres use a three-dose vol- ume with the high-dose volume receiving 70 Gy over 35 fractions and the dose to the intermediate and pro- phylactic dose volumes as in Table 11.6 .
CTV1 should include GTV + 1 cm, the whole naso- pharynx and all involved lymph node levels. Following induction chemotherapy, post-chemotherapy residual volumes are outlined as GTV.
CTV2 includes the following regions.
• Posteriorly – the bilateral retropharyngeal nodes when not involved.
• Anteriorly – the posterior third nasal cavity, posterior ethmoid and posterior third maxillary antrum anteriorly.
• Laterally – the bilateral parapharyngeal spaces, pterygoid plates ± pterygoid muscles.
• Superiorly – skull base and fl oor of the sphenoid sinus superiorly including bilateral foramen ovale, carotid canal and foramen spinosum, clivus and petrous tips.
CTV3 includes:
• the upper half of the sphenoid sinus; • the infraorbital fi ssure, orbital apex and
supraorbital fi ssure;
• uninvolved nodal levels at risk of harbouring microscopic disease. Th e at-risk lymph node levels include bilateral levels Ib–Va, Vb, the retrostyloid space and the supraclavicular fossa.
Treatment is planned and delivered using IMRT. Most patients in the UK are treated with external beam radiotherapy, but intracavitary and interstitial brachy- therapy boosts are alternative treatment options to improve dose delivery to the primary tumour in the nasopharynx.
Th e incidence of acute mucositis increases by 30% with the addition of chemotherapy (Lee et al. , 2012 ). Tumour control in NPC is highly correlated with radi- ation dose, and a high dose of at least 70 Gy equivalent is needed for gross tumour eradication .
Prognosis
Th e fi ve-year relative survival by combined (clinical and pathological) AJCC stage for nasopharynx squa- mous cell carcinoma is shown in Table 11.15 .
Table 11.15 Five-year relative survival for nasopharyngeal cancer
Stage Five-year relative survival (%)
1 71.5
2 64.2
3 62.2
4 38.4
11: Management of cancer of the head and neck
treated by transoral surgery and neck dissection or radiotherapy as a single modality achieving compara- ble control and survival rates. Locally advanced stage disease is treated using multimodality to improve out- comes, usually a combination of chemotherapy and radiotherapy with surgery limited to neck dissection, either prior to or following defi nitive treatment.
Tumours of the oropharynx are broadly classifi ed into lateralised and non-lateralised tumours based on the primary site of the tumour in order to determine the treatment of the uninvolved contralateral neck.
Lateralised tumour
• Tumour confi ned to the tonsillar fossa or extending onto or into the adjacent tongue base and/or soft palate by less than 1 cm.
Non-lateralised tumour
• Tonsillar tumour that involves the adjacent tongue/soft palate by more than 1 cm. OR
• A tumour that arises from a midline structure (tongue base/soft palate/posterior pharyngeal wall, vallecula).
A contralateral N0 neck should be treated prophy- lactically in non-lateralised tumours .
Surgery
Early-stage (I and II)
Surgery involves wide local excision using a tran- soral approach (TLM or TORS) with selective neck Subsites of the oropharynx include:
• tonsil; • tongue base; • vallecula; • soft palate;
• posterior pharyngeal wall.
Level II nodes are the fi rst echelon nodes draining the oropharynx. Approximately 60–80% of patients pre- sent with involved lymph nodes and between 15% and 40% of clinically node-negative patients have occult nodal disease. Th e tongue base, soft palate and poster- ior pharyngeal wall are midline structures with a high risk of contralateral neck node involvement .
Risk factors
Th e principal risk factors are tobacco and alcohol use. Despite the reducing use of tobacco, there is an increas- ing incidence of these cancers in younger adults caused by HPV infection. HPV 16 is the commonest subtype.
Clinical presentation
Th e majority of patients present with sore throat and/ or painless neck swelling and/or occasionally foreign body sensation in the throat. Patients with advanced stage present with:
• diffi culty in swallowing and odynophagia; • referred otalgia;
• trismus;
• impaired tongue movement and altered speech.
Investigations and staging
Investigations are detailed in an earlier section. Primary T staging is summarised in Table 11.16 and nodal staging is summarised in Table 11.3 . All patients are staged as in Table 11.4 .
Histology
Squamous cell carcinoma is the commonest histology. Other histological subtypes include adenocarcin- oma, small cell carcinoma, lymphoma and mucosal melanoma.
Treatment overview
Th e treatment of choice depends upon the subsite, stage, morbidity associated with treatment modality and local expertise. Early-stage disease can oft en be
Table 11.16 T staging of oropharyngeal cancers T1 Tumour ≤ 2 cm
T2 Tumour > 2 cm but ≤ 4 cm
T3 Tumour > 4 cm or extension into lingual surface of epiglottis
T4a Moderately advanced local disease: the tumour invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate or mandible
T4b Very advanced local disease: the tumour invades the lateral pterygoid muscle, pterygoid plates, lateral nasopharynx or skull base or encases the carotid artery
• Concurrent chemoradiotherapy.
• Radiotherapy with concomitant cetuximab (where chemotherapy is contraindicated).
• Radiotherapy alone.
• Induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy.
Th e additional benefi t of concurrent chemother- apy decreases with age with no signifi cant benefi t in patients over 70 years of age as a whole. Th e add- ition of chemotherapy in patients over 70 years of age should be carefully considered on an individual basis. Patients with a high risk of systemic metastasis (T4, N2c and N3 neck disease) and those who are symp- tomatic due to large-volume primary tumours are considered for neoadjuvant chemotherapy. Th ere is an increasing trend to use TPF in this group of patients with good performance status, following a recent meta-analysis (Blanchard et al. , 2013 ).
Patients with bulky resectable neck disease (N2a and above), particularly those not suitable for systemic therapy, are considered for neck dissection, either before or aft er completion of radiotherapy .
Radiotherapy planning
All patients needing radiotherapy (defi nitive and adju- vant) are immobilised, scanned and outlined as detailed previously. Two outlining protocols for oropharyngeal tumours are commonly used in the UK: anatomical and volumetric (or geometric).
CTV1 (Step 2) with these diff erent approaches includes:
• anatomic – the entire oropharynx from the soft palate to the bottom of the hyoid for all subsites; • volumetric – the GTV and 1 cm around the
tumour (edited for bone, air and natural barriers): this method relies on accurately identifying the tumour on the planning CT scan. CTV2 (Step 3) includes:
• all at-risk uninvolved lymph node levels as per Table 11.17 .
All curative intent patients should be routinely planned using intensity modulation to spare the parot- ids (contralateral) in order to reduce the incidence of long-term xerostomia because forward planned con- formal treatment is associated with a higher incidence of severe xerostomia (83% versus 29% at 24 months; Nutting et al ., 2011 ). Figure 11.1 shows a radiotherapy dissection (ipsilateral or bilateral) based on the lateral-
isation of the tumour.
Patient selection is crucial and is based on exam- ination fi ndings under anaesthesia (mobile tumour not fi xed to constrictors) and imaging, with the anticipation that surgery will achieve clear resection margins and would avoid adjuvant treatment where possible. Th e most common subsite for transoral resection is the tonsil, although a small proportion of early tongue base tumours can also be resected using TORS. Results from TLM and TORS studies show good oncologic and functional outcomes (Moore and Hinni, 2013 ).
Open surgery with lip split mandibulotomy, resec- tion of primary tumour and reconstruction with a free fl ap is not recommended due to the associated mor- bidity of poor long-term swallowing function aff ecting quality of life.
Locally advanced stage (III and IV)
Th e role of surgery in advanced stage disease is lim- ited to neck dissection (prior to or following chemo- radiotherapy) in the defi nitive setting or as a salvage for patients who have persistent or relapsed disease following defi nitive treatment. Salvage surgery for locoregional disease off ers a small chance of long-term survival and usually involves a total glosso-pharyngo- laryngectomy and reconstruction .