63 Oropharyngeal Carcinoma
There has been significant debate in the management of oropharyngeal cancer in the last decade, especially considering the increased incidence, clarification of the role of the human papilloma virus (HPV) and the treatment responsiveness of HPV-positive cancers. This is reflected in changes on assessment, staging and treatment paradigms.
63.1 Anatomical Boundaries of the Oropharynx
1. Anterior wall (glossoepiglottic area):
a. Base of tongue (posterior to the circumvallate papillae or posterior third).
2. Lateral wall:
b. Tonsillar fossa and tonsillar (faucial) pillars.
c. Glossotonsillar sulci (tonsillar pillars).
3. Posterior wall (from the level of the hard palate to the hyoid bone or floor of vallecula).
4. Superior wall:
a. Inferior surface of soft palate.
Oropharyngeal squamous cell carcinoma (OPSCC) will dominate this chapter, but there are other oro-pharyngeal tumours which are noteworthy as they are seen in clinical practice and asked about in examinations. Oropharyngeal tumour pathology is as follows:
• Oropharyngeal squamous cell carcinoma: 85%.
• Non-Hodgkin’ s lymphoma (NHL): 10%.
• Minor salivary gland carcinoma (MSGC): 2%.
• Others, for example, rhabdomyosarcoma, melanoma: 3%.
Ninety-five percent of NHL involves the palatine or lingual tonsil. Most MSGC arises from the lateral wall, of these 50% are adenoid cystic. Most soft palate MSG tumours are pleomorphic adenomas. The majority of OPSCC affects the tonsil (45%) or the tongue base (40%) with the soft palate (15%) and posterior pharyngeal wall (5%) less common. Thirty percent of SCC patients will have either a synchronous second primary or will develop a metachronous second primary within 10 years of presentation. There is a male: female ratio of 5:1 for SCC. Betel nut chewing, smoking tobacco and alcohol are risk factors. Leukoplakia and erythroplakia are premalignant. The incidence of OPSCC is increasing significantly in developed countries. This is due to HPV infection, with HPV 16 being the predominant subtype responsible. The proportion of cases with evidence of HPV infection has risen rapidly and HPV is now responsible for over 70% of OPSCCs in Europe and the United States.
63.3 Clinical Features
Many patients present with a neck lump as the only symptom. Sore throat, referred otalgia, odynophagia and muffled speech (hot potato voice) are common. Trismus is a late symptom and suggests pterygoid involvement. A full head and neck examination is mandatory because of the high incidence of a second primary. OPSCC is either exophytic or ulcerative, but with NHL the tonsil is usually large, vascular and asymmetrical compared to its contralateral partner. Fibre-optic examination should be undertaken to define the superior extent (and any nasopharynx and skull base extension) and inferior limits of the tumour. Palpating the tumour and the neck is important to assess the extent of infiltration of the primary and to assess the size, level, number and fixation of any palpable neck lump. NHL requires early referral and assessment by a haematology oncologist to properly stage and manage the disease.
A magnetic resonance imaging (MRI) scan with gadolinium enhancement will accurately define the extent of soft tissue invasion, such as tongue base spread, and neck node involvement. It is preferred to computed tomography (CT) scanning, but this can be useful to assess bony extent if there is mandibular or skull base invasion. A chest and upper abdomen CT scan is performed for exclusion of distant metastases.
Ultrasound-guided fine-needle aspiration cytology (USSgFNAC) of any palpable neck lump is an accurate method of confirming and staging nodal disease.
Positron emission tomography combined with computed tomography (PET-CT) is useful if there is uncertainty on clinical findings or other imaging results. PET-CT can be used for staging purposes in cases of lymphoma. PET-CT scanning is now also recommended for the assessment of treatment response in OPSCC approximately 3 months post-chemoradiotherapy, particularly in patients with advanced nodal disease. In the United Kingdom, PET-Neck trial, PET-CT–guided active surveillance showed similar survival outcomes to the planned neck dissection arm, but resulted in considerably fewer neck dissections, and fewer complications, and was cost-effective, supporting its use in routine practice. PET-CT is also useful in surveillance for recurrent disease.
Panendoscopy under general anaesthesia is necessary to properly assess the extent of the primary tumour and whether it is resectable and to check the hypopharynx, oesophagus, trachea and bronchi for synchronous disease. If disease is limited to the tonsil, an intra-lesional tonsil biopsy is preferred to a tonsillectomy as transoral laser resection may be subsequently used as a definitive treatment. Suspicious tongue base lesions will require a deep biopsy as the cancer can be submucosal.
HPV testing in OPSCC aids stratification of treatment outcomes. The immunohistochemical identification of overexpression of p16 protein is a useful screening method for HPV infection as HPV-associated carcinomas show strong nuclear and cytoplasmic expression of p16 in over 70% of malignant cells and p16-negative cases are almost certainly not HPV associated. Carcinomas showing p16 overexpression should have the presence of HPV confirmed by high-risk HPV DNA in situ hybridisation.
63.5 Staging Summary
The eighth edition of the UICC/AJCC TNM staging system now reflects the importance of HPV-associated oropharyngeal cancer and has a separate classification for p16-positive disease. Essentially it is recognised that T4a stage has similar outcome in p16-positive disease with T4b (i.e., the outcome is similar even if tumour invades pterygoids, lateral nasopharynx and skull base, or encases carotid artery), so there is no separation of these. In respect of N stage, it is recognised that nodal extension (extracapsular spread [ECS]) will not be a significant factor if the tumour is p16 positive. Prognosis is dependent on stage at presentation as well as HPV status. HPV-positive OPSCC has a 58% reduction in the risk of death compared with HPV-negative OPSCC with 3-year overall survival rates of over 80% for HPV-positive disease compared with approximately 55% for HPV-negative disease.