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More than 95% of patients presenting with malignant hypopharyngeal tumours are proven to be squamous cell carcinomas. They usually present as a surface mucosal lesion, but occasionally malignant tumours may arise from ducts of minor salivary glands, or from lymphoid tissue, and therefore may originate below the surface of the visible mucosa. Early surface lesions are usually squamous cell carcinoma presenting as leukoplakic or erythroplakic areas.

Cancers of the hypopharynx are generally aggressive in their behaviour and demonstrate a natural history that is characterised by diffuse primary tumour with mucosal and submucosal local spread, early cervical nodal metastasis, and a relatively high rate of distant spread. Some 80% of all hypopharyngeal carcinomas arise from the piriform sinuses [1], with primary tumours of the posterior pharyngeal wall, the postcricoid region and the oesophageal inlet accounting for > 10%, in most reported series. The incidence of carcinoma is much higher in men than in women, but in the postcricoid region, the reverse is true in the developed world (frequently in association with sideropenic anaemia). Tumours of the piriform fossa can be subdivided into those originating from the lateral or from the medial wall. Tumours of the lateral wall tend to invade the carotid sheath and thyroid gland. Tumours of the medial wall usually invade the aryepiglottic fold and other supraglottic structures, and the postcricoid region invades the larynx. This spread fixes the arytenoid cartilage and the vocal cord resulting in hoarseness. Tumours of the piriform fossa at presentation are frequently found to present with bilateral cervical lymph node metastasis. Aggressive invasion is a common feature, and tumours in the neck may spread along muscle or facial planes for a variable distance from the visible primary mucosal lesion. Bone and cartilage usually act as a barrier to spread, and these structures generally are spared during the initial early tumour growth and when invasion is present signifies a late event of the disease process. However, some 25–45% of all piriform sinus cancers show thyroid cartilage invasion [2].

At initial diagnosis, > 60–70% of all hypopharyngeal cancer patients will be with stage IV disease, 14%+ will have advanced T and/or N stage localised disease [3, 4], and some 5% of patients will present with distant metastases, and almost 40% will have a significant reduction in performance status [3]. The delay in making a diagnosis has most commonly resulted from either a paucity of early symptom in the course of the disease or a failure to adequately address the seriousness of the symptoms by the patient or the clinician, and is the most frequent reason to explain why most patients with hypopharyngeal cancers are diagnosed at an advanced stage of disease. A visible or palpable neck metastasis is the most frequent presenting symptom or sign for the majority of patients. Cancers arising in the hypopharynx do not commonly invade or interfere with vocal fold vibration until they have extended outside of the hypopharynx to involve the larynx, and hoarseness as a symptom in general is considered a late indicator of advanced cancer. The two most common symptoms at presentation of hypopharyngeal cancer are dysphagia and a palpable neck mass, each of which is present in > 50% of patients (Chapter 2). This presentation of hypopharyngeal cancer at an advanced stage with metastasis to the cervical lymph nodes has been attributed to factors other than a delay in diagnosis. It has been suggested that the extraordinary rate of highly anastomotic regional lymphatic drainage of the hypopharynx leads to the early dissemination of cancer to involve the cervical lymph nodal groups [4–6]. The lymphatics of the pharyngeal walls terminate primarily in the jugular chain group of lymph nodes and secondarily in the spinal accessory chain. Retropharyngeal lymph node involvement is also frequent at an early stage of disease (Chapter 2).

The aggressive course of hypopharyngeal cancer has also been attributed to the tendency for this cancer to arise in nutritionally and immunologically depleted patients. A majority of patients have a history of heavy indulgence of drinking alcohol, and an addiction to tobacco and chewing of the areca nut (Chapter 1). Approximately 15% of patients will not be suitable for curative surgery and/or radiotherapy. More than 50% of all patients treated with curative intent will eventually relapse locally, regionally or at distant sites, and the vast majority of these will not be suitable for any curative salvage treatment options [7–9] and over time, 20–25% of patients will be diagnosed with second primary tumours (most frequently located in the head and neck region, in the lung or in the oesophagus). Five percent of patients will experience a third or fourth primary tumours [10, 11]. Prognosis for carcinoma of hypopharynx is considered by most clinicians to be the worst among all head and neck sites.

It is generally accepted that squamous cell carcinoma of the head and neck result from a multistep process of accumulated genetic alterations. At least 4–6 events involving oncogenes and tumour-suppressor genes appear to be necessary for tumour development [12]. Tumours may arise from a single and well-defined mucosal site, or within a diffuse and ill-delimited so-called carcinogenic field. The oncogenic effects of nutritive carcinogens encountered over a lifetime can lead to the occurrence of multiple mucosal sites of epithelial dysplasia that finally will progress to invasive cancer. Field cancerisation is in part responsible for the multiple, synchronous primary malignant lesions that occur in many hypopharyngeal cancer patients. The “field cancerisation” hypothesis proposes that long-term carcinogenic exposure (e.g., from tobacco use and/or alcohol consumption) results in a “condemned mucosa” containing many mutated cells, from which multifocal independently arising (polyclonal) tumours develop. This theory has been widely accepted. In recent years, however, doubts have been raised about the classical explanation of field cancerisation, and a monoclonal origin has been hypothesised [13]. A newer model for the origin of field cancerisation postulates areas of histopathological abnormality surrounding malignant and premalignant lesions, with an extension of several centimetres within which a dysplastic progression can be observed. These are proposed to be derived from a common progenitor clone. Subsequent genetic events produce genetic divergence and different genetic alterations, resulting in a variety of histopathologically diverse regions in an anatomical area. There is relatively little work on the timing of these changes, and some mechanisms may have an early facilitatory effect from which cancer may arise by further mutation [14].

The complete characteristics of the early period of cancer development have largely been elucidated in recent years [12]. The natural history of cancer is a multistage process, and many characteristics of major stages are now well described. They occur over a variable period of time; there is a period of latency – often many years in duration – during which early development occurs at the cellular and microscopic levels. The generally accepted stages are initiation, promotion and progression. The processes of invasion and metastasis can be considered part of progression or as separate stages. Initiation is a rapid and irreversible process caused by exposure to a carcinogenic agent, while promotion is a more prolonged process consequent to repeated or continuous exposure to a substance which may not be carcinogenic or capable of initiating the process.