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Tonsil Cancer
Introduction
Tonsil cancer is the most common form of oropharyngeal malignancy, and its incidence is sharply rising due to the increasing prevalence of human papillomavirus (HPV)-induced cancers. The presence of HPV can dramatically alter the prognosis of tonsillar cancer, and there have recently been significant changes made to the WHO classification and TNM staging to reflect this. Tonsil cancer can be managed by both surgical and oncological approaches, although the optimal treatment regimen remains an area of ongoing research.
Etiology
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Etiology
Traditionally, oropharyngeal and tonsil cancers were attributed to smoking and alcohol misuse, with the former remaining an independent indicator of poor prognosis. In more recent years; however, there has been a sharp increase in the number of cases occurring secondary to HPV, with up to 93% of new oropharyngeal cancers in Western Europe showing HPV positivity.[1] Additionally, there is a growing body of evidence to suggest having a spouse with HPV-related cancer can result in a slight increase in the likelihood of developing oropharyngeal and anogenital cancers.[2]
Epidemiology
Large epidemiological studies have shown tonsils are the most common site of oropharyngeal cancer, compromising 23.1% of all malignancies in this anatomical region, with an overall incidence rate of 8.4 cases per 100,000.[3] Of concern, the rate of tonsil and oropharyngeal cancers has increased dramatically in the last 40 years. This significant rise has been attributed to the "viral epidemic" of HPV, with western countries seeing an increase in the proportion of HPV-associated cancers from 42.5% before 2000 to 72.2% between 2005 and 2009. Conversely, was not a significant increase in the rate of non-HPV oropharyngeal cancers within the same period.[4]
Histopathology
HPV is a double-stranded DNA virus implicated in a host of carcinomas throughout the body. HPV 16 has the greatest association with oropharyngeal cancers, with other oncogenic strains including HPV 18 being less common[5]. p16 is a tumor-suppressor protein that is overexpressed in HPV-positive tumors and is well established as a useful surrogate marker of HPV in tonsil cancer.[6]
The fourth edition of the World Health Organization's Classification of Head and Neck Tumors has made a number of changes to reflect our current understanding of the disease. Oral and oropharyngeal cancers are now separate clinical entities, due to the presence of lymphoepithelial tissues within areas such as the tonsils. Most tonsil cancers are squamous cell carcinomas (SCC). However, the WHO classification now subdivides this into two distinct morphological groups; HPV positive and HPV negative. HPV positive SCCs arise from the deep lymphoid tissue of the tonsillar crypts and have a non-keratinising morphology. HPV negative SCC develops from the oropharyngeal/tonsil surface epithelium and is associated with keratinizing dysplasia.[7]
History and Physical
Tonsillar cancers can have a highly variable clinical history. Patient's may have complaints of a sore throat, unilateral otalgia, or sensation of a mass in the throat, with trismus being a concerning sign of local invasion. Others may be asymptomatic and referred as an incidental finding of asymmetrical tonsils. The tonsil's rich lymphatic supply means many tumors present as an occult lesion with enlarged cervical nodes, in particular within the jugulodigastric region. It is vital to ask the patient about red flag symptoms including weight loss, odynophagia, dysphagia, and persistent hoarseness. Thorough past medical history and discussion of etiological factors including smoking, increased alcohol intake and risk behaviors (e.g., intravenous drug use) may help elicit an underlying cause.
HPV-positive tumors will typically present in younger non-smoking patients of either gender, while HPV-negative tumors will present in older male smokers with more co-morbidities, and thus have a poorer prognosis overall.
Patients require a full ear, nose, and throat examination by an experienced otolaryngologist, including palpation of the neck for cervical lymphadenopathy and close inspection of the oropharynx. Particular attention should be paid to the tonsil beds as primary cancers can be missed within the tonsil crypts. Flexible nasal endoscopy should be performed in all patients for a thorough assessment of the oropharynx including inspection of the tonsils, tongue base, vallecula, and lateral pharyngeal wall for signs of local invasion.
Evaluation
Imaging
All cases of tonsillar cancer will need through pre-treatment cross-sectional imaging, with contrast-enhanced MRI providing the best quality soft tissue delineation of the primary disease and local spread.[8] CT can also assess the primary disease although an artifact from adjacent dental treatments often limits this. CT is currently the imaging modality of choice for staging all head and neck cancers and should be performed from skull base to diaphragm to look for associated nodal and pulmonary disease.[9]
PET-CT can also be used in tonsil cancer as a means to help with diagnosis and staging in difficult to detect cancers[10] and in post-treatment surveillance.[11]. However, it is limited by its false-positive findings, frequently showing uptake in contralateral tonsils,[12] tongue base and Waldeyer's ring[10] without the presence of malignancy.
Endoscopy
It is strongly recommended all suspected tonsillar cancers undergo an examination under anesthesia and panendoscopy.[13] This can facilitate close assessment and biopsy of the disease, planning of surgical interventions, and exclusion of secondary malignancies within the upper airway and esophagus. FNA biopsies have been used in those who are unfit for surgery; however, the reliability of HPV testing in cytology samples has been questioned.[14]
Treatment / Management
Surgical Management
Early tonsil cancer is preferably managed with single modality treatment, with transoral robotic surgery (TORS) and transoral laser microsurgery (TLM) having comparable oncological outcomes.[15] TORs is growing in popularity and has been shown to have reduced operating time, shorter hospital stay, and improved swallowing recovery compared to open techniques[16]; although, persistent severe dysphagia can occur post-operatively.[17] TLM is less widely adopted and involves removal of the tumor in several pieces, making a histological examination of margins difficult.[13] Regardless of the method of surgical intervention, it is advised to remove both tonsils at time of surgery due to a small rate of bilateral synchronous tonsillar cancers.[18](B2)
In more advanced disease, TLM or TORS can still be offered for early T3 tumors; however, this is often not possible for T4 malignancies. Most of these cases will instead undergo chemoradiotherapy, as a surgical intervention will usually require a mandibulotomy and extensive surgical reconstruction resulting in poor post-operative functional outcomes.[13]
Given the high rate of nodal disease in both early and advanced tonsillar cancer, it is recommended that most cases undergoing surgical intervention should also have an elective level II to IV neck dissection.[19](B3)
Oncological Management
Primary radiotherapy for early tonsillar cancer has been shown to have good oncological outcomes and overall survival. Unilateral radiotherapy to levels II to IV can be used in non-lateralized cancers with a low rate of contralateral nodal recurrence and improved rates of radiation toxicity.[20] It is advised to treat those with contralateral nodes with bilateral radiotherapy.[13]
A previous Cochrane review has established chemoradiotherapy as the management of choice for advanced tonsil and oropharyngeal cancers.[21] This avoids the need for extensive surgery which carries significant long-term morbidity and often requires post-operative chemoradiotherapy. Radiotherapy in addition to concurrent platinum-based cisplatin chemotherapy is the most widely used regime, with the monoclonal antibody cetuximab being used as an equally effective alternative in cases where cisplatin is contraindicated (renal impairment and hearing loss).[22](A1)
Differential Diagnosis
The histological differential diagnosis of suspected tonsillar cancer includes;
Staging
Tonsil malignancy is staged as oropharyngeal cancer according to the AJCC TNM classification of malignant tumors. The 2016 eight edition splits oropharyngeal cancer into p16 positive and negative cancers to reflect the current understanding of the influence of HPV and p16 on the prognosis and management.[28] This marks a dramatic change from previous editions of the manual, and can significantly alter the final staging of the malignancy.
T Classification Oropharyngeal Cancers
- T1: Tumor 2 cm or less
- T2: Tumor more than 2 cm but less than 4 cm
- T3: Tumor greater than 4 cm or extension into the lingual surface of epiglottis
- p16 negative tumors
- T4a: Tumor invades larynx, deep/extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible
- T4b: Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base; or encases carotid artery
- p16 positive tumors
- T4: Larynx, deep/extrinsic muscle of tongue, medial pterygoid, hard palate, mandible, lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base; or encases carotid artery
N Classification p16 Negative
- N0: No regional lymph node metastasis
- N1: Single ipsilateral node less than 3 cm
- N2
- N2a: Single ipsilateral node greater than 3 cm but less than 6cm
- N2b: Multiple ipsilateral nodes less than 6 cm
- N2c: Bilateral and contralateral nodes less than 6cm
- N3
- N3a: Single node greater than 6 cm
- N3b: Single or multiple nodes with extra-capsular spread
N Classification p16 Positive
- N0: No regional lymph node metastasis
- N1: Unilateral nodes all less than 6 cm
- N2: Contralateral or bilateral nodes all less than 6 cm
- N3: Metastasis greater than 6 cm
M Classification
- M0: No distant metastasis
- M1: Distant metastasis
Prognosis
Prognosis of tonsil cancer is dependent on the HPV status of the tumor, with HPV positive tumors showing a 5-year overall survival of 71% compared to 46% in HPV negative disease in one study.[29] However, this survival benefit can be negated by the presence of smoking, with mortality rates being significantly higher in HPV-positive smokers compared to non-smokers.[30] Other factors including low volume tumors, lack of nodal disease, young age, low comorbid status, and presence of tumor invading lymphocytes are thought to influence prognosis in oropharyngeal tumors positively.[31] There are no studies directly comparing survival outcomes in tonsil cancers managed with a single modality surgical or oncological management.
Complications
Untreated tonsillar cancer will result in gradual growth and invasion of local structures. Invasion of the lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base and encasement around the carotid is suggestive of unresectable T4b disease in p16 negative cancers. Moreover, invasion of the skull base and vertebral tissues can interfere with emerging nerves, resulting in Horner's syndrome and palsies of the brachial plexus and phrenic nerve. Encasement of the carotid artery can cause a life-threatening carotid blow-out.
The management options of tonsil cancer can also carry significant complications. TORS can result in significant pain and dysphagia postoperatively, particularly in advanced disease. Radiotherapy frequently causes mucositis, xerostomia, and skin reactions, which can also have a significant impact on swallowing.[32] These effects can be amplified in those who undergo TORS resection with post-operative chemo-radiotherapy, who have reported significantly worse swallowing and quality of life outcomes compared to those undergoing single modality treatments.[33]
Consultations
- Otolaryngologists
- Oncologists
- Radiologists
- Plastic/maxillofacial surgeons
- Restorative dentists
- Clinical nurse specialists
- Dieticians
- Speech and language therapists
- Palliative care
Deterrence and Patient Education
Advice on alcohol and smoking cessation should be offered to all patients given their etiological and prognostic influence. HPV vaccination is a controversial topic within the lay media, and although numerous studies have established their effectiveness in the prevention of gynecological malignancies, there is little evidence supporting their use in tonsillar cancers. Moreover, the lack of a pre-malignant stage (as seen in cervical CIS) and differences in HPV epidemiology between cancers could present barriers to its effectiveness.[34] Nevertheless, vaccination of females and males in several countries including the United Kindom, United States, Canada, and Australia is hoped to reduce the rates of oropharyngeal cancers long term.
Enhancing Healthcare Team Outcomes
Management of tonsil cancer requires an interprofessional approach. The initial investigation occurs within the otolaryngology outpatient setting, with the involvement of radiology and pathology departments proving vital for definitive diagnosis and clinical staging. Otolaryngologists and oncologists will ultimately manage the disease with a specialist interest in head and neck cancer; however, support is required from speech and language therapists, nurse specialists, and dietician teams to manage the resultant swallowing, emotional, and nutritional issues. For those undergoing radiotherapy, a review by restorative dentistry is necessary to avoid debilitating osteoradionecrosis.
Media
(Click Image to Enlarge)
Tonsillar mass Image courtesy S Bhimji MD
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