Primary cervical esophageal carcinoma (CEC) is uncommon, located between the inferior border of the cricoid cartilage and the thoracic inlet, and accounts for approximately 5% of all esophageal cancers. Most cases of CEC are diagnosed at advanced stages, frequently involving adjacent anatomical structures. Given its proximity to the larynx, hypopharynx, thyroid, cervical trachea, and upper mediastinum, CEC may extend to these structures. Similarly, cancers such as hypopharyngeal carcinoma, thyroid carcinoma, and cervical tracheal cancer can spread to the cervical esophagus. The cervical esophagus has abundant lymphatic drainage, and CEC commonly metastasizes to the supraclavicular, central cervical, and/or mediastinal lymph nodes. Patients with CEC are prone to developing secondary primary cancers of the upper aerodigestive tract.
Etiology and Risk Factors
The etiology and pathogenesis of CEC are not fully understood. Certain regions have higher incidences, including Japan, Iran, Central Asia, Mongolia, northern China, and South Africa's Eastern Cape province, though no evidence supports a hereditary predisposition.
Environmental factors appear to play a more significant role. Excessive smoking and alcohol consumption are key contributors. Mutations in enzymes involved in ethanol metabolism, such as alcohol dehydrogenase-1B (ADH-1B) and aldehyde dehydrogenase-2 (ALDH-2), are linked to the development of upper digestive tract tumors. Additional risk factors include a preference for foods high in nitrites, consumption of hard or excessively hot foods, overeating quickly, poor oral hygiene, and fungal infections, which are potential triggers for esophageal cancer.
The potential association between human papillomavirus (HPV) infection and the incidence of CEC remains controversial. Regions with high rates of esophageal cancer also exhibit a higher prevalence of HPV infection among esophageal squamous cell carcinoma patients (over 10% of cases). HPV types 16 and 18 are most commonly associated with esophageal cancer.
Pathology
The majority of esophageal cancers are squamous cell carcinomas, followed by adenocarcinomas. Early-stage lesions are confined to the mucosa and may exhibit polypoid growth protruding into the lumen. Alternatively, the tumor may infiltrate the esophageal wall circumferentially, narrowing the lumen, or invade deeper tissues, reaching the mediastinum or pericardium.
Early-stage esophageal cancer is categorized as carcinoma in situ or early invasive carcinoma (T1) without lymph node metastasis. Based on gross pathology, early esophageal cancer can be classified into four types: occult type, erosive type, plaque type, and papillary type, with the erosive and plaque types being the most common. Advanced-stage esophageal cancer can also be divided into four types: medullary, stenotic, fungating, and ulcerative. Medullary-type cancer invades all layers of the esophageal wall circumferentially, resulting in tubular thickening with high malignancy; cross-sections appear grayish-white and brain-like in texture. Stenotic-type cancer, also known as sclerosing cancer, grows circumferentially, causing luminal narrowing. Fungating-type cancer grows into the lumen with prominent, mushroom-like margins. Ulcerative-type cancer forms depressed ulcers that extend into the muscular layer.
Clinical Manifestations
Early symptoms of CEC are nonspecific and may include discomfort while swallowing, a sensation of a foreign body, changes in eating habits, and pain. Middle-to-late-stage symptoms are characterized by progressive dysphagia, which can lead to an inability to ingest food or water in severe cases. Advanced-stage tumors may result in persistent pain due to outward invasion. Recurrent laryngeal nerve involvement can cause persistent hoarseness. It is noteworthy that because of the unique anatomical location of the cervical esophagus, misdiagnosis or missed diagnosis is common and should be given attention.
Diagnosis
The diagnosis of esophageal cancer should encompass histopathological confirmation, determination of lesion location, and TNM staging. Non-invasive imaging modalities form the cornerstone of diagnostic evaluation. These include esophageal barium swallow studies, esophagoscopy/gastroscopy (such as endoscopic ultrasound or narrow-band imaging endoscopy), and enhanced CT and MRI scans of the neck and upper mediastinum.
Treatment
The treatment of cervical esophageal carcinoma (CEC) should be determined by an individualized treatment plan developed after multidisciplinary team (MDT) discussions.
Early-stage Cervical Esophageal Cancer
Endoscopic resection or concurrent radiochemotherapy (CRT) can be performed.
Advanced Cervical Esophageal Cancer
Since CEC is often locally advanced at the time of diagnosis, infiltrating adjacent anatomical structures such as the cricoid cartilage, thyroid cartilage, hypopharynx, thyroid gland, and upper mediastinum, an optimal treatment approach has not been established. Clinical management differs from that of esophageal cancer affecting the lower two-thirds of the esophagus. The National Comprehensive Cancer Network (NCCN) currently recommends concurrent radiochemotherapy (CRT), which preserves laryngeal function and achieves survival rates comparable to surgical treatment. However, CRT as a standard treatment for CEC lacks robust evidence.
Currently, three treatment approaches are commonly used for CEC:
Surgery + Postoperative Radiochemotherapy/CRT
This includes:
- Laryngeal-sparing surgery + cervical esophagectomy: Reconstruction of cervical esophageal defects in a single stage using free jejunal grafts, local pedicled musculocutaneous flaps, free skin flaps, or free musculocutaneous flaps.
- Total laryngectomy, total pharyngectomy, and total esophagectomy + gastric pull-up or colonic interposition surgery.
Neoadjuvant Chemotherapy
Agents such as cisplatin and fluorouracil/paclitaxel may be used, potentially in combination with immunotherapy. Surgery may then be performed based on the degree of tumor regression (surgical resection is preferred if tumor regression is less than 70%), or CRT may be administered (CRT is preferred if tumor regression is greater than 70% or if complete response is achieved). Studies have shown that this approach improves overall survival and laryngeal preservation rates compared to surgery or CRT alone.
Preoperative or Definitive CRT
This approach preserves laryngeal function but may result in side effects from radiochemotherapy.
For patients with CEC who are resistant to radiochemotherapy or experience recurrence after CRT, surgery remains an effective option.