The pharynx is located at the back of the mouth and nasal cavity. The pharynx, a muscular organ covered with a tube-shaped mucosa about 12 cm long, begins at the back of the nose and ends at the top of the trachea and esophagus. The pharynx is an organ that allows nutrients to be transmitted to the stomach and breath. In other words, it serves between the trachea and the esophagus. On the one hand, it allows air drawn by breathing to be transmitted to the lungs, and on the other hand, it pushes nutrients in the mouth into the pharynx. As food passes through the pharynx, the entrance part of the trachea is closed.
Pharynx i.e. pharynx; oropharynx (just behind the mouth), hypopharynx (larynx – near the larynx) and nasopharynx (where the throat joins the nose-upper part) consists of 3 parts. The nasopharynx (upper pharynx), which we will describe in this section, is the upper part of the pharynx, located at the back of the nose and oral cavity. Cancer of the nasopharynx (upper pharynx) begins in this area. Nasopharynx cancer, known as one of the head and neck cancers, is usually common in Asian countries. Although this type of cancer is more common in old age, it can also be observed in people at a young age
Anything that changes the chances of contracting the disease is a risk factor for us. For this reason, it is possible to reduce the risk factors that have an impact on cancer by paying attention to our lifestyle, habits that we have acquired, and all the environmental factors that we are exposed to.
Some risk factors, such as smoking, drinking alcohol, are habits that we acquire in life and can be changed. There are also some risk factors, such as a person’s age and family history, that cannot be changed. On the other hand, just because you have a risk doesn’t mean you’ll get cancer. Or it can be said that you have cancer without any risk factors.
For this reason, it is important to know the active risk factors for nasopharynx cancers. In this way, you can reduce the risk with small changes that you will make in your life. If you have certain risk factors associated with Nasopharynx cancer, you should not neglect your routine checks at frequent intervals. In this way, you can have an early diagnosis and effective treatment of cancer.
Now, let’s examine the risk factors that are factors in nasopharynx cancer together.
Studies have shown that pickled meat and fish, which are consumed a lot, play a role in the development of nasopharynx cancer. In addition, it is known that eating vegetables and fruits can reduce the risk of this type of cancer.
Viruses can play a role in the development of certain types of cancer. The virus can cause genetic changes in cells that can then turn into cancer. Many people can be affected by viruses that can cause cancer, but not cancer. Viruses can only lead to cancer in some cases.
Cancer of the upper pharynx (nasopharynx) has been found to be associated with Epstein Barr virus (EBV). On the other hand, cancer has not been detected in many people who are carriers of EBV. The relationship between EBV infection and nasopharynx cancer is quite complex, and the cause is not yet fully understood. However, EBV infection alone cannot cause nasopharynx cancer. How this virus contributes to the development of nasopharynx cancer depends on how a person’s genes deal with this virus.
In addition, research has shown that there may be a link between some types of upper pharynx (nasopharynx) cancer and the human papillomavirus (HPV).
Some studies have shown that smoking may be a risk factor for the development of all nasopharynx cancers, especially keratinized squamous cells. Again, some studies have found that drinking a large amount of alcohol poses a risk of this type of cancer. But in order for these results to be accurate, more research is needed.
People with chronic inflammation of the ear, nose, and throat may have an increased risk of upper pharynx cancer (nasopharynx). Chronic nasal congestion and inflammation, middle ear infection and polyps are the causative factors in this type of cancer.
A person’s genes can affect the risk of nasopharynx cancer. The tissue structures of people in different blood groups are also different. These different structures affect the body’s response to the immune system. Therefore, how the body reacts to EBV infection can be associated with the development of cancer.
If a person has an inherited tissue structure, it means that they are at high risk of developing nasopharynx. Earlier detection of nasopharynx cancer in family members will increase the likelihood of hereditary tissue structure in the person and therefore the risk of developing cancer.
Nasopharynx cancer usually does not show symptoms. Person most of the time;
However, it is not true that these symptoms are directly associated with Nasopharynx cancer. Other non-serious health problems can also lead to such symptoms. In this case, it is up to you to consult a specialist doctor without wasting time. In this way, it will be possible to find a quick solution to the health problem detected early.
Tumors in the nasal region
Several different types of tumors appear to develop in the nasopharynx. Some of them consist of benign tumors, while some may be malignant. Now let’s examine these types of cancer together.
Nasopharyngeal carcinoma, which begins in epithelial cells (cells covering the inner and outer surfaces of the body), is the most common type of cancer in the nasopharynx.
It is known that there are three different types of nasopharyngeal carcinoma.
Although these types of cancer look different from each other, they actually develop from the same type of cell. This type of cell is epithelial cells that line the surface of the nasopharynx. In this direction, the treatment methods used in all types of nasopharynx cancer are usually the same.
Benign tumors in the nasopharynx are more common in teenagers and children and are quite rare. It can be said that tumors of this type do not spread throughout the body and usually do not pose a vital threat. If necessary, the treatment is different from the treatment of nasopharynx cancer.
Is early diagnosis and screening possible for nasopharynx cancer? How is it diagnosed?
During physical examination, the symptoms of nasopharynx cancer are investigated by looking at the nose, mouth, throat, facial muscles and lymph nodes in the neck in the head and neck area, and the person’s history of this disease is examined and the family history of nasopharynx cancer is questioned.
The nasopharynx (upper body) is deep in the head area and is not easily visible. For this reason, the area is examined using special techniques. There are two methods used to look for possible cancer development, bleeding, if any, or other signs of the disease. In one of the methods applied, the back of the throat is illuminated to examine the nasopharynx and nearby areas and this area is examined with special small mirrors (indirect nasopharyngoscopy). Another method is; a thin tube with a light tip called a nasopharyngoscope is inserted through the nose and examined directly on the surface of the nasopharynx (direct nasopharyngoscopy). In this method, it is often used for nasopharynx examination, as the examination can be done in more detail.
If the tumor has begun to develop below the surface of the nasopharynx (lower mucous layer), it is difficult to detect by physical examination. Therefore, in suspicious cases, imaging and laboratory tests are resorted to for more detailed examination.
Imaging tests use X-rays, magnetic fields, sound waves, or radioactive material. Imaging tests are tests performed to determine whether the suspicious area has cancer, to detect the spread of cancer, to determine the effectiveness of treatment, and to examine the tendency of cancer to recur.
Chest X-ray, Computed Tomography (CT), magnetic resonance imaging (MRI), and PET tomography are common imaging tests used to diagnose nasopharynx cancers.
When nasopharynx cancer is diagnosed, a chest X-ray is taken to check the spread of the cancer to the lungs. If the cancer is limited to the area where it is already located and does not progress, it is not possible to see it in other areas (lungs). Buddha gives us information about the state of cancer spread.
Computed tomography takes cross-sectional images of the body using X-rays. Unlike a chest X-ray, a CT scan provides a clear view of the suspicious area by injecting contrast material into the body, and then a large number of more detailed images are taken from different angles.
CT imaging applied to the head and neck area gives information about the location, shape and size of the tumor and allows you to detect growing lymph nodes associated with cancer. CT and MRI imaging are important screening tests that examine possible cancer development in the bones at the base of the head. CT can also be used to determine the spread of cancer to other parts of the body.
MRI takes a detailed image of the soft tissues in the body. It uses radio waves and powerful magnets instead of x-rays when performing imaging. Energy from radio waves is absorbed and sent to the suspect area. The computer converts the resulting image into detailed sectional images. It is possible to get a more detailed image with the contrast agent given before viewing.
MRI can be used to determine possible cancer development in structures near the nasopharynx. It is better at imaging soft tissues in the throat and nose than CT. However, both methods (CT and MRI) are not sufficient in the imaging of the base of the head, where nasopharynx cancer often develops.
A radioactive isotope (fluorodeoxyglucose) called FDG, which is a sugar derivative and emits positron radiation, is injected into the patient through a vein to show functional changes that occur in organs and tissues. Cancer cells adhere to the injected isotope by sensing this sugar from which they feed. The Pet machine detects these cancer cells that stick.
A PET that displays the entire body is an imaging test that detects the spread of cancer to the lymph nodes and other areas.
Some technological machines can perform both PET and BT imaging. More detailed imaging can be achieved with this technique.
Blood tests, which are rarely used to diagnose nasopharynx cancer, detect the spread of cancer to other parts of the body.
Most patients with nasopharyngeal cancer have signs of Epstein-Barr virus-related infection in their blood. Measuring the level of DNA in the Epstein-Barr virus (EBV), which plays an active role in this type of cancer, plays an important role in determining the course of the disease.
Symptoms and physical examination findings may indicate that the person has nasopharynx cancer. But the actual diagnosis is made by examining cell samples taken from the suspicious area in a laboratory environment. This process is called a biopsy. Different biopsy methods can be used depending on the location of the suspicious area.
Endoscopic biopsy: during nasopharynx examination, a biopsy sample is taken from the suspected area using small instruments with a fiber optic microscope and the type of cancer is determined by examination. This is an easy procedure done in the form of outpatient treatment.
Fine needle aspiration biopsy: a fine needle aspiration biopsy can be used if there is a suspicious swelling in the neck or near the neck. In this process, a thin needle is inserted into the suspicious swelling and a liquid sample containing cells and small tissue particles is taken. Local anesthesia may be required from time to time where the needle enters. The liquid sample taken is examined in laboratory environment and the presence of possible cancer is determined.
A fine needle biopsy can detect cancer that begins in the lymph nodes (lymphoma), the spread of the cancer to other areas, or the expansion of the lymph nodes in the neck area due to infection.
When nasopharynx cancer is diagnosed, its staging or spread status must be determined. In this way, the treatment plan to be applied is shaped. Staging is determined by the state of the cancer’s spread to the nasopharynx (upper pharynx) or other parts of the body, and, if it has spread, which parts of the body it has spread to. In other words, it can also be called Measuring the depth and breadth of the disease. Sometimes, the stage of cancer can be determined during diagnosis, or additional tests may be required to be performed to be sure. After that, effective treatment planning is done by looking at the nasopharynx and the state of cancer spread.
It is important to know the area of spread of the disease and how aggressive it is when staging. Stages sorted from 0 to IV show the degree of cancer progression. The most advanced stage of cancer is expressed by the number IV. Stage 0 indicates that the cancer is at an early stage. In Upper pharynx cancer, we can briefly explain the properties expressed by each universe as follows:
Stage 0: The Cancer is at the first place (in situ). Cancer cells are only in the surface layer of the nasopharynx and have not yet spread deeper. In addition, it did not progress to nearby lymph nodes or distant areas.
Stage I: the tumor is in the nasopharynx and may spread to the soft tissue of the wide cavity and/or oropharynx (just behind the mouth). But it does not spread to nearby lymph nodes or distant areas of the body.
We can observe Stage II of nasopharynx cancer in 2 ways;
Stage IIA: the tumor has developed inside the tissues on the left or right side of the upper part of the throat.
Stage IIB: the cancer may still be limited to the nasopharynx or may have spread to the soft tissue of the wide cavity or oropharynx (just behind the mouth) or to the right or left side of the upper throat. One or more tumor spreads not greater than 6 cm in the nearby lymph nodes. These lymph nodes can be one of the lymph nodes on one side of the neck or on both sides of the throat (retropharyngeal lymph nodes). The cancer has not spread to remote areas.
We can observe stage III of nasopharynx cancer in 2 ways;
Stage IIIA: the tumor may have spread to the sinuses or bones near the nasopharynx. In addition, it may or may not be visible in the lymph nodes behind the throat or in the neck, but the growth in these lymph nodes is not more than 6 cm. The cancer has not spread to remote areas.
Stage IIIB: the tumor may still be confined to the nasopharynx or may have spread to the soft tissue of the wide cavity or oropharynx (just behind the mouth) or to the right or left side of the upper throat. The tumor may have spread to the nearby lymph nodes on both sides of the neck, but the growth in these lymph nodes is not more than 6 cm. The cancer has not spread to remote areas.
We can observe stage III of nasopharynx cancer in 2 ways;
Stage IVA: the tumor has spread to the head and/or head (cranial) nerves, the hypopharynx (lower part of the throat), eyes, or nearby tissues. Spread may or may not occur in the nearby lymph nodes located in the neck. The growth in these lymph nodes is not more than 6 cm. The cancer has not spread to remote areas.
Stage IVB: the tumor may or may not progress to nearby soft tissues or bones. In addition, spread can be seen in the lymph nodes located in the shoulder area above the clavicle. It is observed that these lymph nodes are larger than 6 cm. The cancer has not spread to remote areas.
Stage IVC: the tumor may or may not progress to nearby soft tissues or bones. It has spread or not to nearby lymph nodes. But it is found that the cancer has spread to remote areas.
Chemotherapy is a drug therapy used to kill cancer cells. Chemotherapy treatment includes cancer drugs used by oral or intravenous injection. These drugs are effective in treating all cancers that circulate throughout the body through the bloodstream and spread throughout the body beyond the head and neck area of the cancer.
Chemotherapy is used as the first treatment method for advanced nasopharynx cancer, since some drugs used to treat chemotherapy are more sensitive to radiation. This method of treatment, in which chemotherapy and radiation therapy are administered in combination, is called chemoradiotherapy. Chemotherapy can be administered alone or in combination with radiation therapy if nasopharynx cancer spreads to distant organs (such as the lungs, bones, or liver). Chemotherapy (adjuvant therapy) after radiation therapy is a preventive treatment used to reduce the likelihood of cancer recurrence.
The most commonly used chemotherapy drug for the treatment of nasopharynx cancer is cisplatin. It can usually be used alone as part of chemoradiotherapy, or the effectiveness of treatment can be increased by simultaneous radiation therapy in combination with 5-fluorouracil (5-FU). In addition, cisplatin and 5-FU combined therapy can be used after radiation therapy to prevent recurrence of the cancer.
Carboplatin (Paraplatin®), doxurubicin (Adriamycin®), epirubicin (Ellense®), paclitaxel (Taxol®), docetaxel (Taxotere®), gemcitabine (Gemzar®), bleomycin and methotrexate are chemotherapy drugs that can be useful in the treatment of advanced nasopharynx cancer that has spread. In patients with favorable health conditions, it is aimed to increase the effectiveness of treatment by using two or more of these drugs in combination.
As we learn more about cancer-causing changes within the cell, new drugs targeting these changes continue to be developed. These targeted drugs work differently than standard chemotherapy drugs. In cases where chemotherapy drugs cannot be effective in treatment, targeted drugs may be preferred.
Cetuximab is a monoclonal antibody (synthetic immune system protein) that targets the epidermal growth factor receptor (EGFR). EGFR is a protein found on the surface of cells and normally receives signals for cell growth and division. A cell with Nasopharynx cancer sometimes has enough EGFR to accelerate growth. Setuximab slows or stops rapid growth in EGFR. This drug is mostly used in combination with chemotherapy and/or radiation therapy if the cancer continues to develop or recur after chemotherapy treatment.
The main role of cetuximab in the treatment of nasopharynx cancer remains a subject of research.
Cancer of the upper pharynx is close to the brain, a vital organ, and the rapid spread of the cancer through the blood tract and lymphatic system limits the use of surgical treatment methods. For this reason, treatment methods that are usually at the forefront of chemotherapy and radiation therapy are preferred. In addition, targeted treatments are one of the methods used according to the course of the disease.
Radiation therapy is the treatment method that is almost identified with Nasopharynx cancer. However, chemotherapy and radiation therapy can be administered simultaneously to increase the effect of treatment in nasopharynx cancer. This method of treatment, known as chemoradiotherapy, may be more effective than radiotherapy alone.
Radiation therapy aims to kill cancer cells or slow their development using high-energy X-rays or particles. This method of treatment is applied as part of the main treatment for nasopharynx cancers.
Chemotherapy and radiation therapy can be administered simultaneously to increase the effect of treatment in nasopharynx cancer. This method of treatment, known as chemoradiotherapy, may be more effective than radiotherapy alone.
In nasopharynx cancer, radiation therapy is usually applied to both the main tumor and the nearby lymph nodes in the neck. Although no growth or abnormalities have been detected in the lymph nodes, it is used to prevent the possible spread of cancer. Different methods of radiation therapy can be used to treat nasopharynx cancer:
Intensity-adjusted radiation therapy is a sensitive treatment that sends high doses of radiation to the targeted area or directly to the tumor. Radiation sent directly to the target, which is displayed in three dimensions with millimetric calculations, manages to minimize damage to healthy tissues. In this way, the patient has fewer side effects than conventional radiotherapy methods.
Proton therapy is one of the methods of external radiotherapy. This method aims to destroy cancer cells using protons instead of X-rays. Proton therapy may be a treatment option for advanced nasopharynx cancers located close to the brain, spinal cord and central nervous system.
Stereotactic radiotherapy is aimed at destroying the tumor in 3-5 sessions by applying high doses of radiation to the target set in three dimensions. This method provides a serious advantage, especially in tumors smaller than 4 cm.
Brachytherapy is a method applied by placing a high-power source of radioactive rays in cancer cells. Thanks to this beam source placed inside, it is possible to give a high dose of radiation to the cancer area. This application minimizes side effects as it does less damage to healthy tissues.
In case of recurrence of cancer after external radiation therapy, brachytherapy method can also be used from time to time. Sometimes it is aimed to increase the effectiveness of treatment with both internal and external radiation therapy.
Nasopharynx cancer is a type of cancer in which surgery is difficult to perform, as it is close to vital organs such as the brain and has a rapid spread. Some of the nasopharynx tumors can be removed using flexible fiber optic microscopes and long, thin surgical instruments with new endoscopic surgical techniques. But this practice is only an option for a small number of patients to benefit from mainstream treatments such as radiotherapy.
Cancer of the nasopharynx often progresses to the lymph nodes in the neck. Although this type of cancer mostly responds positively to radiation therapy, it is sometimes observed that some cancer is left behind after treatment. In this case, lymph nodes can be removed by neck dissection. This method varies depending on where the tumor is located and its spread.
For example, only lymph nodes close to the area where the main tumor is located and the cancer is likely to spread can be removed (partial neck dissection). Or the lymph nodes on one side of the neck, located between the jawbone and collarbone, and some muscles and nerve tissues are removed. The main nerve extending to the shoulder muscle is usually not removed (modified radical neck dissection). Another option is the removal of muscles, nerves and vessels along with almost all the lymph nodes on one side of the neck (radical neck dissection).
The food and Drug Administration of America (FDA) approved the use of the drug pembrolizumab (Keytruda), an immunotherapy drug for the treatment of head and neck cancers, on August 5, 2016. Of head and neck cancer (BBK) the most common types of flat (squamous cell carcinoma and the anatomical regions are in contact with the weather most common place this cancer (mouth, pharynx, nasal – pharynx, the larynx, etc.). Here is Pembrolizumab, repeated or spread (metastatic = 4. stage) is approved for squamous cell BBK, whose disease worsens under or after platinum-based chemotherapy.
174 BBK patients were taken to the study that approved pembrolizumab for head and neck cancers, including laryngeal cancer, and the administration dose of the drug was determined as 10 mg/kg every 2 weeks or 200 mg every 3 weeks. 16% of patients received a significant response to treatment (objective response rate = objective response rate). In 23 of the 28 patients who responded well to treatment, this positive response lasted 6 months or longer (up to 27.7 months).
The most common side effects associated with treatment were reported as weakness, loss of appetite, and difficulty breathing (dyspnea), hypothyroidism.
Hyperthermia for the treatment of head and neck cancers, when combined with radiotherapy, increases the full response rate by about 25%, which is one of the most important indicators of treatment success, and it can do so without causing additional side effects. For this reason, integrating hyperthermia into the treatment of head and neck cancers is an application with a high level of evidence (level 1 evidence).
Hyperthermia, also known as heat therapy or thermotherapy, is a complementary cancer treatment method applied by exposing body tissue to high heat (39 to 44 °C).
Research has shown that high heat damages or kills cancer cells, with little damage to normal tissues. Hyperthermia can shrink a tumor by killing cancer cells and damaging proteins and structure in cells.
Click here for detailed information about hyperthermia – heat treatment in nasopharynx cancer.
What are the innovations in nasopharynx cancer research and treatment?
Causes, prevention and early diagnosis
Several studies are being conducted investigating how the Epstein-Barr virus (EBV), which has a significant share in the formation of nasopharynx cancers, is transmitted and how it triggers cancer in nasopharynx cells.
The researchers hope that these studies will eventually be vaccinated to protect against certain types of nasopharynx cancer caused by EBV infection.
Recent findings about EBV allow its interaction with Nasopharynx cells and the immune system’s reaction to EBV with new blood tests to predict early detection of nasopharynx cancer and better responsive treatment. Studies are being conducted in places around the world where this cancer is common.
Advances in Skull Surgery allow techniques such as endoscopy used from the nose to remove tumors in hard-to-reach areas. This type of surgery requires a team that specializes in this area. This technique may be of hope to nasopharynx cancer patients who have relapsed and keratinized nasopharynx cancer patients who have not responded to radiotherapy.
Most radiotherapy techniques use X-rays. Another radiotherapy technique kills cancer cells using protons. Unlike X-rays, protons cause minor damage to tissues at certain distances by energizing them before and after contact with their targets. In other words, in this way, proton beam radiation can be obtained with less intact tissues, while tumors can be more effective on cells. But this technique has not been proven to be better than other next-generation radiotherapy techniques that use X-rays, such as IMRT. In addition, the high cost of proton therapy devices prevents the spread of treatment.
Doctors are also working on the best radiotherapy program. External radiation therapy is applied for weeks within a row, 5 days a week , usually 1 time a day. Studies are being conducted on the possibility of more effective treatments with reduced dose (hypofractionated radiation) twice a day or daily overdose applications.
New chemotherapy drugs, new drug combinations and new ways of delivering drugs that may be more effective against nasopharynx cancer are continuing to be developed. A few types of drugs still in use for other types of cancer; capecitabine, oxaliplatin, and gemcitabine have been produced by Studies against nasopharynx cancer.
Clinical trials are also testing the best combination of chemotherapy and radiotherapy. For example, it compares the effectiveness of chemotherapy according to its administration before, during, or after radiation therapy.
Cetuximab (Erbitux) is the drug that targets the epidermal growth factor receptor (EGFR). EGFR is a protein found on the surface of cells. In nasopharynx cancer, the effect of this targeted drug shows.
Other drugs, including Nimotuzumab and Icotinib, are being studied for use against nasopharynx cancer.
There are also new drugs that target new blood vessels that the tumor needs to expand. These are angiogenesis inhibitors. Several types of drugs, including Bevacizumab (Avastin®), sorafenib (Nexavar®), and pazopanibin (Votrient®), are being tested against nasopharynx cancer.
America’s food and Drug Administration (FDA) approved the use of the drug pembrolizumab (Keytruda), an immunotherapy drug for the treatment of head and neck cancers, including nasopharynx cancer, on August 5, 2016. Of head and neck cancer (BBK) the most common types of flat (squamous cell carcinoma and the anatomical regions are in contact with the weather most common place this cancer (mouth, pharynx, nasal – pharynx, the larynx, etc.). Here is Pembrolizumab, repeated or spread (metastatic = 4. stage) is approved for squamous cell BBK, whose disease worsens under or after platinum-based chemotherapy.
Epstein-Barr virus (EBV) appears to partially cause nasopharynx cancer. Although the immune system of patients reacts to EBV, it seems that it is not sufficient to kill cancer cells. Researchers are working on new ways to support the immune system, or to better target EBV-infected cells.
One way to do this is to inject the cells back into the patient, increasing the number of T-cells, a member of the immune system, taken from the blood of a patient with Nasopharynx cancer, and the power to kill EBV. In a small number of patients, the results of these studies are promising, but it seems that it needs to be improved in large-scale studies.
It has been discovered that certain gene mutations in nasopharynx cells cause cancer. P53, a tumor suppressor gene and a key role in many cancers, is promising to be repaired using the virus. This approach is still being studied.
