Cervical Cancer

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Cervical cancer is a type of cancer caused by a virus called HPV and occurs in the cervix or the lower part of the uterus – where babies develop during pregnancy. The virus is spread through sexual contact. Most women are able to fight HPV infection. However, in some cases, viruses cause cancer. You are at higher risk if you smoke, have many children, use birth control pills for a long time, or are infected with HIV.

Cervical cancer may not cause any symptoms at first. Then, you may experience pelvic pain or vaginal bleeding. It usually takes several years for normal cells in the cervix to turn into cancer cells. Health care providers can find abnormal cells by doing a Pap Smear test to examine the cells from the cervix. You may also be required to do an HPV test. If you have abnormal test results, you may need a biopsy or other tests.

Treatment may include surgery, radiation therapy, chemotherapy, or a combination. Treatment options depend on the size of the tumor, whether the cancer has spread, and whether you wish to remain fertile.

Vaccines can protect against certain types of HPV, including some that can trigger cancer.

Overview of Cervical Cancer

Cervical cancer is a disease in which malignant (cancer) cells form in the cervical tissue.

The cervix is ​​the narrow, lower end of the uterus (the hollow, pear-shaped organ where the fetus grows). The cervix leads from the uterus to the vagina (birth canal).

Organs in the female reproductive system include the uterus (womb), ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer lining called the myometrium and an inner lining called the endometrium.

Cervical cancer usually develops slowly over time. Before cancer appears in the cervix, cervical cells undergo a change known as dysplasia, in which abnormal cells begin to appear in the cervical tissue. Over time, the abnormal cells can become cancer cells and begin to grow and spread deeper into the cervix and to the surrounding area.

Cervical cancer in children is a rare case.

Risk Factors of Cervical Cancer 

Anything that increases your chances of getting a disease is called a risk factor. Having a risk factor does not mean you will get cancer; not having risk factors does not mean you will not get cancer. Talk to your doctor if you think you may be at risk for cervical cancer.

Risk factors for cervical cancer include the following:

  • Infected with the human papillomavirus (HPV). This is the highest risk factor for cervical cancer.
  • Exposed to DES (diethylstilbestrol) medications during pregnancy

In women infected with HPV, the following risk factors increase the risk of cervical cancer:

  • Given birth to many children.
  • Have smoking habits.
  • Use oral contraceptives (“birth control pills”) for a long time

There are also other risk factors that increase the risk of HPV infection:

  • Have a weak immune system caused by immunosuppression. Immunosuppression weakens the body’s ability to fight infections and other diseases. The body’s ability to fight HPV infection can be reduced by long-term immunosuppression due to:
    • Infected with the human immunodeficiency virus (HIV).
    • Consumption of medication to help prevent transplant rejection
  • Being sexually active at a young age.
  • Have multiple sexual partners.

Advancing age is a major risk factor for most cancers. The chances of getting cancer increase as you age.

Signs and Symptoms of Cervical Cancer 

Early stage of cervical cancer may not cause signs or symptoms. Women should undergo routine checkups, including tests to examine the presence of human papillomavirus (HPV) or abnormal cells in the cervix. The prognosis (chance of recovery) is better when cancer is discovered early. 

Check with your doctor if you experience any of the following:

  • Vaginal bleeding (including bleeding after sexual intercourse).
  • Unusual vaginal discharge.
  • Pelvic pain.
  • Pain during sexual intercourse.

Diagnosis and Prognosis of Cervical Cancer

Diagnosis

The following procedures can be used to diagnose cervical cancer:

  • Physical test and medical history: A physical test is done to check for general signs of health, including checking for signs of disease, such as lumps or anything else that looks unusual. A medical history review of the patient’s previous illnesses and treatments will also be conducted. 
  • Pelvic test: This test examines the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. A speculum is inserted into the vagina, with the doctor or nurse looking at the vagina and cervix to check for any signs of disease. A Pap test of the cervix is usually conducted. Your doctor or nurse will also insert a gloved finger or two lubricated from one hand into the vagina and place the other hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. In addition, they may also insert a lubricated gloved finger into the rectum to feel for any lumps or abnormal areas.
  • Pap test: A test procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, brush, or a small wooden stick is used to gently scrape the cells from the cervix and vagina. The cells are viewed under a microscope to see if they are abnormal.
  • Human papillomavirus (HPV) test: A laboratory test used to check DNA or RNA for certain types of HPV infection. Cells are taken from the cervix and DNA or RNA from the cells is examined to see if the infection is caused by a type of HPV linked to cervical cancer. This test can be done using a cell sample taken during the Pap test. This test may also be done if the Pap test results show certain abnormal cervical cells.
  • Endocervical curettage: A procedure to remove cells or tissue from the cervical canal using a curette (spoon-shaped instrument). Tissue samples are taken and examined under a microscope for signs of cancer. This procedure is sometimes performed along with colposcopy.
  • Colposcopy: A procedure in which a colposcope (a device that lights up and enlarges) is used to examine the vagina and cervix for abnormal areas. Tissue samples can be taken using a curette (spoon-shaped instrument) or a brush and examined under a microscope for signs of disease.
  • Biopsy: If abnormal cells are found in a Pap test, the doctor may do a biopsy. A tissue sample is cut from the cervix and viewed under a microscope by a pathologist to check for signs of cancer. Biopsy procedure that only removes a small amount of tissue can be done in a doctor’s office. Women may need to go to the hospital for a cervical cone biopsy (removal of a larger, cone-shaped sample of cervical tissue).

Prognosis

The prognosis (chances of recovery) of cervical cancer depends on the following:

  • Stage of cancer (the size of the tumor and whether it affects part of the cervix or the entire cervix, or has spread to lymph nodes or other body parts).
  • Type of cervical cancer.
  • Patient’s age and general health.
  • Whether the patient has a specific type of human papillomavirus (HPV).
  • Whether the patient is infected with human immunodeficiency virus (HIV).
  • Whether the cancer has recently been diagnosed or has recurred

Treatment options depend on the following:

  • Stage of cancer
  • Type of cervical cancer.
  • The patient’s desire to have children.
  • Patient’s age.

Stages of Cervical Cancer 

The process used to identify whether cancer has spread within the cervix or to other body parts is called staging. The staging process determines the stage of the cancer. It is important to know the cancer staging in order to determine the right treatment.

The following tests and procedures can be used in the staging process:

  • CT scan (CAT scan): A procedure that produces a series of detailed images of areas inside the body taken from multiple angles. The images are created by a computer connected to an x-ray machine. The dye can be injected into a vein or swallowed to help an organ or tissue appear more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • PET scan (positron emission tomography scan): A PET scan is a procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and creates images of where glucose is being used in the body. Malignant tumor cells appear brighter in the image because they are more active and take up more glucose than normal cells.
  • MRI (magnetic resonance imaging): A procedure that uses magnets, radio waves, and a computer to create a series of detailed images of internal body organs. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Ultrasound examination: A procedure in which high-energy sound waves (ultrasound) are reflected from internal tissues or organs, creating echoes. The echoes form an image of body tissue called a sonogram. This image can be printed for later viewing.
  • Chest x-ray: X-ray scan to see the inside of your chest. An x-ray is a type of energy beam that can penetrate your body and onto film — creating images of areas inside the body, such as the lymph nodes.
  • Cystoscopy: A procedure to look inside the bladder and urethra to check for abnormal parts. A cystoscope is inserted through the urethra into the bladder. A cystoscope is a thin, tube-like instrument with a light and lens for viewing. The cystoscope also may have an instrument to remove tissue samples, which are examined under a microscope for signs of cancer.
  • Laparoscopy: A surgical procedure to look at the organs in the stomach to check for signs of disease. A small incision is made in the abdominal wall and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments can be inserted through the same or another incision to perform procedures — such as removing an organ or taking tissue samples to be examined under a microscope for signs of disease.
  • Pre-treatment surgical staging: Surgery is done to find out if cancer has spread within the cervix or to other body parts. In some cases, cervical cancer can be removed at the same time. Pre-treatment surgical staging is usually performed only as part of a clinical trial.

The results of this test are reviewed together with the results of the original tumor biopsy to determine the stage of cervical cancer.

How Cancer Can Spread In The Body 

Cancer can spread through the tissues, lymph system, and blood:

  • Tissues. Cancer spreads from where it started by spreading to nearby areas. 
  • Lymph system. The cancer spreads from where it started by getting into the lymph system. Cancer spreads through lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it started by getting into the blood. Cancer spreads through the blood vessels to other body parts

When cancer spreads to other parts of the body, it is called metastasis. Cancer cells break away from where they started (the main tumor) and spread through the lymph or blood systems.

  • Lymph system. Cancer gets into the lymph system, spreads through the lymph vessels, and forms tumors (metastatic tumors) in other body parts
  • Blood. Cancer enters the blood, spreads through the blood vessels, and forms tumors (metastatic tumors) in other parts of the body.

Metastatic tumors are the same type of cancer as primary tumors. For example, if cervical cancer spreads to the lungs, the cancer cells in the lungs are actually cervical cancer cells. The disease is metastatic cervical cancer, not lung cancer.

The following are stages to determine cervical cancer:

Carcinoma in Situ (Stage 0)

In carcinoma in situ (stage 0), abnormal cells are found in the innermost lining of the cervix. These abnormal cells can become cancerous and spread to nearby normal tissue.

Stage I

In stage I, cancer is found only in the cervix.

Stage I is divided into stages IA and IB, based on the number of cancers found.

Stage IA:

In stage IA1, the cancer is no more than 3 millimeters deep and no more than 7 millimeters wide. In IA2 stage, the cancer is more than 3 millimeters but not more than 5 millimeters deep, and no more than 7 millimeters wide.

A very small number of cancers that can only be seen with a microscope are found in cervical tissue.

Stage IA is divided into stages IA1 and IA2, based on tumor size.

  • In stage IA1, the cancer is no more than 3 millimeters deep and no more than 7 millimeters wide.
  • In stage IA2, the cancer is more than 3 millimeters but not more than 5 millimeters deep, and no more than 7 millimeters wide.

Stage IB:

In stage IB1, the cancer can only be seen with a microscope and is more than 5 mm deep and more than 7 mm wide OR the cancer can be seen without a microscope and is 4 cm or smaller. In stage IB2, the cancer is larger than 4 cm.

Stage IB is divided into stages IB1 and IB2, based on tumor size.

  • In stage IB1:
    • Cancer can only be seen with a microscope and is more than 5 millimeters deep and more than 7 millimeters wide; or
    • Cancer can be seen without a microscope and is no more than 4 cm.
  • In stage IB2, the cancer can be seen without a microscope and is more than 4 cm 

Stage II

Cancer has spread beyond the cervix, but not to the pelvic wall or to the lower third of the vagina. In stages IIA1 and IIA2, cancer has spread beyond the cervix to the vagina. In stage IIA1, the tumor can be seen without a microscope and is 4 cm or smaller. In stage IIA2, the tumor can be seen without a microscope and is larger than 4 cm. In stage IIB, cancer has spread outside the cervix to the tissue around the uterus.

In stage II, cancer has spread outside the uterus but not to the pelvic wall (the tissue that lines the body parts between the hips) or to the lower third of the vagina.

  • Stage II is divided into stages IIA and IIB, based on the extent to which the cancer has spread.
  • Stage IIA: Cancer has spread beyond the cervix to the upper two thirds of the vagina but not to the uterine tissue. Stage IIA is divided into stages IIA1 and IIA2, based on tumor size.
    • In stage IIA1, the tumor can be seen without a microscope and is no larger than 4 cm.
    • In stage IIA2, the tumor can be seen without a microscope and is more than 4 cm tall.
  • Stage IIB: Cancer has spread beyond the cervix to the tissue around the uterus but not to the pelvic wall.

Stage III

In stage III, cancer has spread to the lower third of the vagina, and / or to the pelvic wall, and / or has caused kidney problems.

Stage III is divided into stages IIIA and IIIB, based on how far the cancer has spread.

  • Stage IIIA:

Cancer has spread to the lower third of the vagina but not to the pelvic wall.

  • Stage IIIB:

Cancer has spread to the pelvic wall; and / or the tumor has become large enough to block the ureter (the tube that connects the kidney to the bladder). This blockage can cause the kidneys to enlarge or stop working.

Stage IV

In stage IV, cancer has spread beyond the pelvis, or can be seen in the lining of the bladder and / or rectum, or has spread to other parts of the body.

Stage IV is divided into stages IVA and IVB, based on where the cancer has spread.

  • Stage IVA:

The cancer has spread to nearby organs, such as the bladder or rectum

  • Stage IVB:

Cancer has spread to other parts of the body, such as the lymph nodes, lungs, liver, intestines, or bones.

Cancer has spread to other body parts, such as the liver, lungs, bones, or distant lymph nodes.

Recurrent Cervical Cancer

Recurrent cervical cancer is cancer that comes back (returning) after being treated. Cancer may come back in the cervix or in other parts of the body.

Treatment for Cervical Cancer

Various types of treatment are available to treat cervical cancer. Some are standard treatments, and some are still in clinical trials. A clinical trial is research intended to help improve current treatments or gather information about new treatments for cancer patients. When clinical trials show that the new treatment is better than standard treatment, the new treatment can become standard treatment. Certain clinical trials are only open to patients who have not undergone any treatment. 

Four Types of Standard Treatments Used: 

Surgery

Surgery (surgical removal of the cancer) is sometimes used to treat cervical cancer. The following surgical procedures can be used:

Cervical conization

A procedure to remove cone-shaped pieces of tissue from the cervix and cervical canal. The pathologist views the tissue under a microscope to look for cancer cells. Conization can be used to diagnose or treat cervical conditions. This procedure is also called a cone biopsy.

Conization can be performed using one of the following procedures:

  • Cold knife conization: A surgical procedure that uses a scalpel (sharp knife) to remove abnormal or cancerous tissue.
  • Loop electrosurgical excision procedure (LEEP): A surgical procedure that uses an electric current through a thin wire loop as a knife to remove abnormal tissue or cancer.
  • Laser surgery: A surgical procedure that uses a laser beam (a narrow, intense beam) as a knife to create a bloodless wound in the tissue or to remove surface lesions such as tumors.

The type of conization procedure used depends on where the cancer cells are in the cervix and the type of cervical cancer.

Total hysterectomy

Surgery to remove the uterus, including the cervix. If the uterus and cervix are removed through the vagina, this procedure is called a vaginal hysterectomy. If the uterus and cervix are removed through a large incision (cut) in the abdomen, then the procedure is called a total abdominal hysterectomy. If the uterus and cervix are removed through small incisions in the abdomen using a laparoscope, the surgical procedure is called a total laparoscopic hysterectomy.

The uterus is surgically removed with or without other organs or tissues. In a total hysterectomy, the uterus and cervix are removed. In total hysterectomy with salpingo-oophorectomy, (a) the uterus plus one (unilateral) ovary and fallopian tube are removed; or (b) the uterus plus both (bilateral) ovaries and fallopian tubes are removed. In a radical hysterectomy, the uterus, cervix, both ovaries, fallopian tubes, and nearby tissue are removed. This procedure is performed using a low transverse or vertical incision.

  • Radical hysterectomy: Surgery to remove the uterus, cervix, parts of the vagina, and large areas of ligaments and tissue around these organs. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed.
  • Modified radical hysterectomy: Surgery to remove the uterus, cervix, upper part of the vagina, and the ligaments and tissues that surround these organs. Nearby lymph nodes can also be removed. In this type of surgery, not as much tissue and / or organs are removed as in a radical hysterectomy.
  • Radical trachelectomy: Surgery to remove the cervix, surrounding tissue and lymph nodes, and the upper part of the vagina. The uterus and ovaries are not removed.
  • Bilateral salpingo-oophorectomy: Surgery to remove both the ovaries and fallopian tubes.
  • Pelvic exenteration: Surgery to remove the lower colon, rectum, and bladder. The cervix, vagina, ovaries, and nearby lymph nodes are also removed. Artificial openings (stomas) are made for urine and stool to flow from the body into a collection bag. Plastic surgery may be needed to create an artificial vagina after this surgery.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or prevent them from growing. There are two types of radiation therapy:

  • External radiation therapy uses a machine outside the body to deliver radiation towards the cancer. Certain ways of providing radiation therapy can help keep radiation from damaging nearby healthy tissue. An example of external radiation therapy is Intensity-modulated radiation therapy (IMRT): IMRT is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of varying intensity (strength) are aimed at the tumor from various angles. This type of external radiation therapy causes less damage to nearby healthy tissue.
  • Internal radiation therapy uses a radioactive substance that is sealed in a needle, granule, wire, or catheter that is placed directly in or near the cancer.

Radiation therapy is based on the type of cancer. External and internal radiation therapy are used to treat cervical cancer, and may also be used as palliative therapy to relieve symptoms and improve quality of life.

Chemotherapy

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Either via oral or injection chemotherapy, the drugs enter the bloodstream and reach cancer cells throughout the body (systemic chemotherapy). Chemotherapy is placed directly into the cerebrospinal fluid, organs, or body cavities (e.g. the stomach), or the drugs may mainly affect cancer cells in the areas concerned (regional chemotherapy). Chemotherapy will depend on the type and stage of cancer. 

Targeted Therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without damaging normal cells.

Monoclonal antibody therapy uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that can stimulate the growth of cancer cells. Antibodies attach to the substance and kill cancer cells, block their growth, or prevent them from spreading. Monoclonal antibodies are given through intravenous infusion. Antibodies can be used independently or are delivered directly to the cancer cells through medications, toxins, or radioactive materials.

Bevacizumab is a monoclonal antibody that binds to a protein called vascular endothelial growth factor (VEGF) and can prevent the growth of new blood vessels that tumors need to grow. Bevacizumab is used to treat cervical cancer that has metastasized (spread to other parts of the body) and recurrent cervical cancer.

Follow-up tests may be required

Some of the tests done to diagnose cancer or to identify the stage of the cancer can be repeated. Several tests will be repeated to see how well the treatment is working. The decision on whether to continue, change, or stop treatment can be determined based on the results of the tests.

Certain tests will continue from time to time after treatment ends. The results of tests can show whether your condition has changed or whether the cancer has recurred (returned). This test is sometimes called a follow-up test.

Your doctor may ask if you have any of the following signs or symptoms, which could mean the cancer has returned:

  • Pain in the stomach, back, or legs.
  • Swelling in the leg.
  • Difficulty urinating.
  • Cough.
  • Tiredness

The follow-up tests for cervical cancer are usually done every 3 to 4 months for the first 2 years, then followed by a checkup every 6 months. The tests will include your current health screening.

Stage-based Treatment for Cervical Cancer 

Carcinoma in Situ (Stage 0)

Carcinoma in situ (stage 0) treatment can include the following:

  • Conizations, such as cold knife conization, loop electrosurgical excision procedure (LEEP), or laser surgery.
  • Hysterectomy for women who cannot or do not desire to have more children. This is done only if the tumor cannot be completely removed by conization.
  • Internal radiation therapy for women who cannot undergo surgery.

Stage IA of Cervical Cancer 

  • Stage IA cervical cancer is divided into stages IA1 and stage IA2.

Treatments for stage IA1 may include the following:

  • Conization.
  • Total hysterectomy with or without bilateral salpingo-oophorectomy.

Treatments for stage IA2 may include the following: 

  • Modified radical hysterectomy and removal of lymph nodes.
  • Radical trachelectomy.
  • Internal radiation therapy for women who cannot undergo surgery.

Stage IB and IIA of Cervical Cancer 

Treatment for stage IB and stage IIA cervical cancer may include the following:

  • Radiation therapy is given along with chemotherapy
  • Radical hysterectomy and removal of pelvic lymph nodes with or without radiation therapy to the pelvis, plus chemotherapy.
  • Radical trachelectomy.
  • Chemotherapy followed by surgery.
  • Radiation therapy only.

Stage IIB, III, and IVA of Cervical Cancer

 Treatment for stage IIB, stage III, and stage IVA cervical cancer may include the following:

  • Radiation therapy is given along with chemotherapy at the same time.
  • Surgery to remove pelvic lymph nodes followed by radiation therapy with or without chemotherapy.
  • Internal radiation therapy.
  • Clinical trial of chemotherapy to shrink the tumor followed by surgery.
  • Clinical trials of chemotherapy and radiation therapy are given at the same time, followed by chemotherapy.

Stage IVB of Cervical Cancer

Treatment for stage IVB cervical cancer may include the following:

  • Radiation therapy as palliative therapy to relieve symptoms caused by cancer and improve quality of life.
  • Chemotherapy and targeted therapy.
  • Chemotherapy as palliative therapy to relieve symptoms caused by cancer and improve quality of life.
  • Clinical trials of new anticancer drugs or drug combinations.

Cervical Cancer During Pregnancy 

Treatment for cervical cancer during pregnancy depends on the stage of the cancer and how long the patient has been pregnant. Biopsy and imaging tests can be done to determine the stage of the disease. To avoid exposing the fetus to radiation, MRI (magnetic resonance imaging) is used.

Treatment Options

Carcinoma in Situ (Stage 0) During Pregnancy

Usually, no treatment is required for carcinoma in situ (stage 0) during pregnancy. Colposcopy can be done to detect invasive cancer.

Stage I of Cervical Cancer During Pregnancy

Pregnant women with slow-growing stage I of cervical cancer may be able to delay treatment until the second trimester of pregnancy or after delivery.

Pregnant women with fast-growing stage I of cervical cancer may require immediate treatment. Treatments may include:

  • Conization.
  • Radical trachelectomy.

Women should be tested to see if the cancer has spread to the lymph nodes. If the cancer has spread to the lymph nodes, immediate treatment is required. 

Stage II, III, and IV of Cervical Cancer During Pregnancy

Treatment for stage II, stage III, and stage IV of cervical cancer during pregnancy may include the following:

  • Chemotherapy to shrink tumors in the second or third trimester of pregnancy. Surgery or radiation therapy can be done after delivery.
  • Radiation therapy and chemotherapy. Talk to your doctor about the effects of radiation on the fetus. It may be necessary to end a pregnancy before treatment begins.

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