Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate nutrition must be assured, and appropriate dental care is essential. Factors that influence treatment decisions include the stage and cellular type of cancer (EAC, ESCC, and other types), along with the person's general condition and any other diseases that are present.

In general, treatment with a curative intention is restricted to localized disease, without distant metastasis: in such cases a combined approach that includes surgery may be considered. Disease that is widespread, metastatic or recurrent is managed palliatively: in this case, chemotherapy may be used to lengthen survival, while treatments such as radiotherapy or stenting may be used to relieve symptoms and make it easier to swallow.

Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin, and either continuously infused fluorouracil or capecitabine.

Radiotherapy is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localised disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent.

Treatment of hypopharyngeal cancer depends on the prognosis (chance of recovery), age, stage, and general health of the patient. Because hypopharyngeal cancer is often advanced at the time of diagnosis, treatment also depends on the overall goal. The goal may simply be to keep the patient talking, eating, and breathing normally.

Treatment usually begins with surgery and then a course of radiation for cancer that has progressed past Stage I. For cancer that is advanced, which is typical of hypopharyngeal cancer, neoadjuvant chemotherapy may be used. This is performed by administering chemotherapy before surgery. Neoadjuvant chemotherapy in conjunction with radiation and surgery has yielded the best results in patients with Stage III and Stage IV cancers.

The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.

Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques, endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that was pioneered in Japan and is available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. A 2016 Cochrane review found low quality evidence of no difference in short-term mortality between laparoscopic and open gastrectomy (removal of stomach), and that benefits or harms of laparoscopic gastrectomy cannot be ruled out.

Those with metastatic disease at the time of presentation may receive palliative surgery and while it remains controversial, due to the possibility of complications from the surgery itself and the fact that it may delay chemotherapy the data so far is mostly positive, with improved survival rates being seen in those treated with this approach.

Chemotherapy in throat cancer is not generally used to "cure" the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of paclitaxel and carboplatin. Cetuximab is also used in the treatment of throat cancer.

Docetaxel-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only taxane approved by US FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced squamous cell carcinoma of the head and neck.

While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and salivary glands from the effects of radiation.

Radiation therapy is the most common form of treatment. There are different forms of radiation therapy, including 3D conformal radiation therapy, intensity-modulated radiation therapy, particle beam therapy and brachytherapy, which are commonly used in the treatments of cancers of the head and neck. Most people with head and neck cancer who are treated in the United States and Europe are treated with intensity-modulated radiation therapy using high energy photons. At higher doses, head and neck radiation is associated with thyroid dysfunction and pituitary axis dysfunction.

Specific treatment depends on the location, type, and stage of the tumour. Treatment may involve surgery, radiotherapy, or chemotherapy, alone or in combination. This is a specialised area which requires the coordinated expertise of ear, nose and throat (ENT) surgeons (Otorhinolaryngologists) and Oncologists. A severely affected patient may require a laryngectomy, the complete or partial removal of the vocal cords.

Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.

Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).

The risk of malignancy is highest in the U.S. in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barrett's esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barrett's esophagus and dysplasia, and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation has an efficacy of 90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to five years and a favorable safety profile.

Proton pump inhibitor drugs have not been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent five-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett esophagus will go on to develop esophageal cancer, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.

Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, nonsteroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in people with Barrett's esophagus. However, none of these studies have been randomized, placebo-controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.

Patients generally respond well to treatment. Iron supplementation usually resolves the anemia, and corrects the glossodynia (tongue pain).

Esophageal webs and rings can be treated with endoscopic dilation.

Cancer of the stomach, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally. Eastern Asia (China, Japan, Korea, Mongolia) is a high-risk area for gastric cancer, and North America, Australia, New Zealand and western and northern Africa are areas with low risk. The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. Important factors that may contribute to the development of gastric cancer include diet, smoking and alcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example, "Helicobacter pylori" or Epstein-Barr virus) and pernicious anemia. Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.

There is risk of perforation of the esophagus with the use of dilators for treatment. Furthermore, it is one of the risk factors for developing squamous cell carcinoma of the oral cavity, esophagus, and hypopharynx.

An important anatomic landmark in anal cancer is the pectinate line (dentate line), which is located about 1–2 cm from the anal verge (where the anal mucosa of the anal canal becomes skin). Anal cancers located above this line (towards the head) are more likely to be carcinomas, whilst those located below (towards the feet) are more likely to be squamous cell carcinomas that may ulcerate. Anal cancer is strongly associated with ulcerative colitis and the sexually transmissible infections HPV and HIV. Anal cancer may be a cause of constipation or tenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form.

Anal cancer is investigated by biopsy and may be treated by excision and radiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%.

Currently, there is no direct treatment for AEN. Only treatment is for the underlying main diseases or conditions. Appropriate hydration is set. Antacids are also added for further recovery support. Common support drugs of antacids are either H receptor antagonists, and/or a proton pump inhibitor. Sucralfate was used as an option. Parenteral nutrition greatly increased chance of recovery. An esophagectomy can be issued if the disorder is severe enough.

Factors that contribute to the development of hypopharyngeal cancer include:

- Smoking

- Chewing tobacco

- Heavy alcohol use

- Poor diet

Smoking, like lung cancer, can cause hypopharyngeal cancer because it contains carcinogens that alter the DNA or RNA in a dividing cell. These alterations may change a normal DNA sequence to an oncogene, a gene that causes cancer after exposure to a carcinogen.

Squamous cells, a type of cell that lines hollow organs like the throat, mouth, lungs, and outer layer of skin, are particularly vulnerable when exposed to cigarette smoke.

Chewing tobacco can have the same effects as smoking and is also linked to hypopharyngeal cancer. The chewing tobacco is placed into the mouth, leaving it exposed to enzymes, like amylase, which partly digests the carcinogenic material. Saliva is swallowed, along with the cancer-promoting material, which passes through the hypopharynx on its way to the esophagus.

Heavy alcohol use is linked to Hypopharyngeal Cancer as well. Alcohol damages the lining of the hypopharynx, increasing the amount of chemicals that are allowed to seep into the underlying membranes. Heavy alcohol use is also associated with nutritional deficiencies.

A disease called Plummer-Vinson syndrome, a genetic disorder that causes a long-term iron deficiency, may also lead to Hypopharyngeal Cancer. Other factors like a deficiency in certain vitamins also appear to contribute to this type of cancer.

Asymptomatic Schatzki rings seldom worsen over time, and need no treatment.

Symptomatic Schatzki rings may be treated with esophageal dilatation, using bougie or balloon dilators. These have been found to be equally effective. Bougie dilatation involves passage of long dilating tubes of increasing size down the esophagus to stretch the area of narrowing, either over a guidewire passed into the stomach by endoscopy (the "Savary-Gillard" system) or using mercury-weighted dilators (the "Maloney" system). This is usually done with intravenous sedation to reduce discomfort. Dilatation can produce some temporary irritation. A short course of proton pump inhibitor therapy may decrease aggravation by stomach acid reflux into the esophagus. The duration of the benefit of dilation varies, but may be from months to years. Dilation may be repeated if narrowing recurs.

Smoking is the most important risk factor for laryngeal cancer. Death from laryngeal cancer is 20 times more likely for heaviest smokers than for nonsmokers. Heavy chronic consumption of alcohol, particularly alcoholic spirits, is also significant. When combined, these two factors appear to have a synergistic effect.

Some other quoted risk factors are likely, in part, to be related to prolonged alcohol and tobacco consumption. These include low socioeconomic status, male sex, and age greater than 55 years.

People with a history of head and neck cancer are known to be at higher risk (about 25%) of developing a second cancer of the head, neck, or lung. This is mainly because in a significant proportion of these patients, the aerodigestive tract and lung epithelium have been exposed chronically to the carcinogenic effects of alcohol and tobacco. In this situation, a field change effect may occur, where the epithelial tissues start to become diffusely dysplastic with a reduced threshold for malignant change. This risk may be reduced by quitting alcohol and tobacco.

Certain foods and lifestyle are considered to promote gastroesophageal reflux, but most dietary interventions have little supporting evidence. Avoidance of specific foods and of eating before lying down should be recommended only to those in which they are associated with the symptoms. Foods that have been implicated include coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods. Weight loss and elevating the head of the bed are generally useful. A wedge pillow that elevates the head may inhibit gastroesophageal reflux during sleep. Stopping smoking and not drinking alcohol do not appear to result in significant improvement in symptoms. Although moderate exercise may improve symptoms in people with GERD, vigorous exercise may worsen them.

The treatments for GERD include lifestyle modifications, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole.

Metaplastic carcinoma is cancer that begins in cells that have changed into another cell type (for example, a squamous cell of the esophagus changing to resemble a cell of the stomach). In some cases, metaplastic changes alone may mean there is an increased chance of cancer developing at the site. Metaplastic carcinoma is a relatively uncommon type of cancer with treatment generally similar to that of invasive ductal carcinoma of no special type.

If it is caused by esophagitis, in turn caused by an underlying infection, it is commonly treated by treating the infection (typically with antibiotics). In order to open the stricture, a surgeon can insert a bougie – a weighted tube used to dilate the constricted areas in the esophagus. It can sometimes be treated with other medications. For example, an H2 antagonist (e.g. ranitidine) or a proton-pump inhibitor (e.g. omeprazole) can treat underlying acid reflux disease.

Several drugs are used to treat DES, including nitroglycerin, hyoscine butylbromide, calcium channel blockers, hydralazine, and anti-anxiety medications. Acid suppression therapy, such as proton pump inhibitors, are often the first line therapy. Botulinum toxin, which inhibits acetylcholine release from nerve endings, injected above the lower esophageal sphincter may also be used in the treatment of DES. Small studies have suggested benefit from endoscopic balloon dilation in certain patients, but all of the above have a low percentage of success in treating the condition; whilst the treatments work in some sufferers, it does not work for everyone. In extremely rare cases, surgery may be considered.

Squamous cell carcinomas, also known as epidermoid carcinoma are a number of different types of cancer that result from squamous cells. These cells form the surface of the skin lining of hollow organs in the body and line the respiratory and digestive tracts.

Common types include:

- Squamous cell skin cancer: A type of skin cancer

- Squamous-cell carcinoma of the lung: A type of lung cancer

- Squamous cell thyroid carcinoma: A type of thyroid cancer

- Esophageal squamous cell carcinoma: A type of esophageal cancer

Despite sharing the name "squamous cell carcinoma", the SCCs of different body sites can show differences in their presented symptoms, natural history, prognosis, and response to treatment.

Anemia associated with Cameron lesions usually responds to oral iron medication, which may be needed for years. Gastric acid suppression may promote lesion healing and a proton-pump inhibitor such as omeprazole is often prescribed. Surgical hernia repair is sometimes needed for indications such as refractory anemia requiring repeated blood transfusions, or anemia combined with other hernia symptoms.