Cervical Cancer

Let's move back a little bit in time to find cause of cancer that my family member suffered. Around 15 years ago, my family member got cervical cancer, and what she suffered today from lymph nodes cancer are most likely cause by this type of cancer (cervical).

So, it might be good idea to find out about cervical cancer today.

Note: Excerpts are copied or re-written from American Cancer Society


What is Cancer?

Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells.

How a normal cell becomes cancer

Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becoes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries.

Because cancer cells continue to grow and divide, they are different from normal cells. Instead of dying, cancer cells outlive normal cells and keep forming new abnormal cells. Another difference between cancer cells and normal cells is that cancer cells can invade (grow into) other tissues. Being able to grow out of control and to invade other tissues makes a cell a cancer cell.

Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. Most of the time, when DNA gets damaged the cell can fix it. If the cell can't repair the damage, the cell dies. In cancer cells the damaged DNA is not repaired, but the cell doesn't die like it should. Instead, this cell goes on making new cells even though the body does not need them. These new cells will all have the same DNA damage as the first cell does.

People can inherit damaged DNA, but most of the time DNA damage is caused by something we are exposed to in our environment. Sometime the cause of the DNA damage is something obvious, like cigarette smoking. But many times no clear cause is found.

A cancer cell has many mistakes in its DNA - having damage in just one spot does not cause cancer. Even when someone inherits damaged DNA, more mistakes in their DNA are needed before a cancer will develop. Staying away from things that are known to damage DNA (like smoking) as a part of a healthy life style lowers the change that more DNA damage will take place. This can reduce the risk of cancer even in people who have an inherited tendency to get cancer.

How cancers grow and spread?

In most cases the cancer cells form a tumour. Some cancers, like leukaemia, do not form tumours. Instead, these cancer cells involved the blood and blood-forming organs and circulate through other tissues where they grow. But sometimes the extra cells in these blood cancers may also form a mass of tissue called a tumour.

Cancer cells often travel to other parts of the body, where they begin to grow and replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

But no matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer.

Not all tumours are cancerous. Tumours that aren't cancer are called benign. Benign tumours can cause problems - they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they can't invade they also can't spread to other parts of the body (metastasise). These tumours are almost never life threatening.

How cancer differ?

Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

How common is cancer?

Cancer is the second leading cause of death in the United States. Nearly half of all men and a little over one third of all women in the US will develop cancer during their lifetimes.

Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking and eating a better diet. Often, the sooner a cancer is found and treatment begins, the better are the changes for living for many years.

What is Cancer of the Cervix?

The cervix is the lower part of the uterus (womb). It is sometimes called the uterine cervix. The body (upper part) of the uterus, is where a foetus grows. The cervix connects the body of the uterus to the vagina (birth canal). The part of the cervix closest to the body of the uterus is called the endocervix. The part next to the vagina is the exocervix (or ectocervix). The place where these 2 parts meet is called the transformation zone. Most cervical cancers start in the transformation zone.

Cervical cancers and cervical pre-cancers are classified by how they look under a microscope. There are 2 main types of cervical cancers: squamous cell carcinoma and adenocarcinoma. About 80% to 90% of cervical cancers are squamous cell carcinomas. These cancers are from the squamous cells that cover the surface of the exocervix. Under the microscope, this type of cancer is made up of cells that are like squamous cells. Squamous cell carcinomas most often begin where the exocervix joins the endocervix.

The remaining 10% to 20% of cervical cancers are adenocarcinomas. Adenocarcinomas are becoming more common in women born in the last 20 to 30 years. Cervical adenocarcinoma develops from the mucus-producing gland cells of the endocervix. Less commonly, cervical cancers have features of both squamous cell carcinomas and adenocarcinomas. These are called adenocarcinomas carcinomas or mixed carcinomas.

Although cervical cancers start from cells with pre-cancerous changes (pre-cancers), only some of the women with pre-cancers of the cervix will develop cancer. The change from pre-cancer to cancer usually takes several years - but it can happen in less than a year. For most women, pre-cancerous cells will go away without any treatment. Still, in some women pre-cancers turn into true (invasive) cancers. Treating all pre-cancers can prevent almost all true cancers.

Pre-cancerous changes are separated into different categories based on how the cells of the cervix look under a microscope.

Although almost all cervical cancers are either squamous cell carcinomas or adenocarcinomas, other types of cancer also can start in the cervix. These other types, such as melanoma, sarcoma, and lymphoma, occur more commonly in other parts of the body.

What are the key statistics about Cervical Cancer?

The American Cancer Society estimates that in 2009, about 11,270 cases of invasive cervical cancer will be diagnosed in the US. Some researchers estimate that non-invasive cervical cancer (carcinoma in situ) is about 4 times more common than invasive cervical cancer.

About 4,070 women will die from cervical cancer in the US during 2009. Cervical cancer was once one of the most common causes of cancer death for American women. The cervical cancer death rate declined by 74% between 1955 and 1992. The main reason for this change is the increased use of the Pap test. This screening procedure can find changes in the cervix before cancer develops. It can also find early cervical cancer in its most curable stage. The death rate from cervical cancer continues to decline by nearly 4% a year.

Cervical cancer tends to occur in mid-life. Most cases are found in women younger than 50. It rarely develops in women younger than 20. Many older women do not realise that the risk of developing cervical cancer is still present as they age. Almost 20% of women with cervical cancer are diagnosed when they are over 65. That is why it is important for older women to continue having regular Pap tests.

Cervical cancer occurs most often in Hispanic women; the rate is over twice that in non-Hispanic white  women. African-American women develop this cancer about 50% more often than non-Hispanic white women.

The 5-year survival rate refers to the percentage of patients who live a least 5 years after their cancer is diagnosed. Five year rates are used to produce a standard way of discussing prognosis. Of course, many people live much longer than 5 years. Five-year relative survival rates assume that some people will die of other causes and compare the observed survival with that expected for people without the cancer. That means that relative survival only talks about deaths from the cancer in question. This is a more accurate way to describe the prognosis for patients with a particular type  and stage of cancer. Five-year rates are used to produce a standard way to discuss prognosis, or outlook for survival. The 5-year relative survival rate for the earliest stage of invasive cervical cancer is 92%. The overall (all stages combined) 5-year survival rate for cervical cancer is about 71%.

Keep in mind that 5-year survival rate are based on patients. diagnosed and initially treated more than 5 years ago. Improvements in treatment often result in a more favourable outlook for recently diagnosed patients.

What are the Risk Factors for Cervical Cancer?

A risk factor is anything that changes women's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for many cancers. But having a risk factor, or even several, does not mean that woman will get the disease.

Several risk factors increase women's change of developing cervical cancer. Women without any of these risk factors rarely develop cervical cancer. Although these risk factors increase the odds of developing cervical cancer, many women with these risks do not develop this disease. When a woman develops cervical cancer or pre-cancerous changes, it may not be possible to say with certainty that a particular risk factor was the cause.

In thinking about risk factors, it helps to focus on those that women can change or avoid (like smoking or human papilloma virus infection), rather than those that women cannot (such as age, and family history). However, it is still important to know about risk factors that cannot be changed, because it's even more important for women who have these factors to get regular Pap tests to detect cervical cancer early.

Cervical cancer risk factors include:
  • Human papilloma virus infection
  • Smoking
  • Immunosuspession
  • Chlamydia infection
  • Diet
  • Oral contraceptives (birth control pills)
  • Multiple pregnancies
  • Low socio-economic status
  • Diethylstilbestrol (DES)
  • Family history of cervical cancer

Do we know what causes Cervical Cancer?

In recent years, scientists have made much progress toward understanding what happens in cells of the cervix when cancer develops. In addition, they have identified several risk factors that increase the odds that a woman might develop cervical cancer.

The development of normal human cells mostly depends on the information contained in the cells' chromosomes. Chromosomes are large molecules of DNA. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance.

Some genes (packets of our DNA) have instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumour suppressor genes. Cancers can be caused by DNA mutations (gene defects) that turn on oncogenes or turn off tumour suppressor genes. Scientists now think that HPV causes the production of 2 proteins known as E6 and E7. When these proteins are produced, they turn off some tumour suppressor genes. This may allow the cervical lining cells to grow uncontrollably, which is some cases will lead to cancer.

But HPV does not completely explain what causes cervical cancer. Most women with HPV don't get cervical cancer, and certain other risk factors, like smoking and HIV infection, influence which women exposed to HPV are more likely to develop cervical cancer.

How Is Cervical Cancer Staged?

The process of finding out how far the cancer has spread is called staging. Information is gathered from exams and diagnostic tests to determine the size of the tumour, how deeply the tumour has invaded tissues within and around the cervix, and the spread to lymph nodes or distant organs (metastasis). This is an important process because the stage of the cancer is the key factor in selecting the right treatment plan.

A staging system is a way for members of the cancer care team to summarise the extent of a cancer's spread. Cervical cancer is staged with the FIGO (International Federation of Gynecology and Obstetrics) System of Staging. This system classifies the disease in stages 0 through IV. It is based on clinical staging rather than surgical staging. This means that the extent of disease is evaluated by the doctor's physical examination and a few other tests that are done in some cases, such as cystoscopy and proctoscopy.

If surgery is done, it may reveal that the cancer has spread more than the doctors initially thought. This new information may change the treatment plan, but it does not change the patient's FIGO stage. This staging system is different from those for other cancers. The systems for other cancers take into account whether the cancer has spread to local lymph nodes. The FIGO doesn't, even though we know the outlook worsens if the cancer has spread to lymph nodes.

Stage 0: The cancer cells are very superficial (only affecting the surface) are found only in the layer of cells lining the cervix, and they have not grown into (invaded) deeper tissues of the cervix. This stage is also called carcinoma in situ (CIS) or cervical intraepithelial neoplasis (CIN) grade III.

Stage I: In this stage the cancer has invaded the cervix, but it has not spread anywhere else.

Stage IA: This is the earliest form of stage I. There is a very small amount of cancer, and it can be seen only under a microscope.
  • Stage IA1: The area of invasion is less than 3 mm (about 1/8-inch) deep and less than 7 mm (about 1/4-inch) wide.
  • Stage IA2: The area of invasion is between 3 mm and 5 mm (about 1/5-inch) deep and less than 7 mm (about 1/4-inch) wide.

Stage IB: This stage includes Stage I cancers that can be seen without a microscope. This stage also includes cancers that can only be seen with a microscope if they have spread deeper than 5 mm (about 1/5 inch) into connective tissue of the cervix or are wider than 7 mm.
  • Stage IB1: The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches).
  • Stage IB2: The cancer can be seen and is larger than 4 cm.

Stage II: In this stage, the cancer has grown beyond the cervix and uterus, but hasn't spread to the walls of the pelvis or the lower part of the vagina.
  • Stage IIA: The cancer has not spread into the tissues next to the cervix (called the parametria). The cancer may have grown into the upper part of the vagina.
  • Stage IIB: The cancer has spread into the tissues next to the cervix.

Stage III: The cancer has spread to the lower part of the vagina or the pelvic wall. The cancer may be blocking the ureters (tubes that carry urine from the kidneys to the bladder).
  • Stage IIIA: The cancer has spread to the lower third of the vagina but not to the pelvic wall.
  • Stage IIIB: The cancer has grown into the pelvic wall. If the tumor has blocked the ureters (a condition called hydronephrosis) it is also a stage IIIB.

Note: In the alternate staging system by the American Joint Committee on Cancer, stage IIIB is defined by the fact that the cancer has spread to lymph nodes in the pelvis.

Stage IV: This is the most advanced stage of cervical cancer. The cancer has spread to nearby organs or other parts of the body.
  • Stage IVA: The cancer has spread to the bladder or rectum, which are organs close to the cervix.
  • Stage IVB: The cancer has spread to distant organs beyond the pelvic area, such as the lungs.

Five-year survival rates by stage

Below are listed the chances a woman will live 5 years after treatment for the various stages of cervical cancer. These are overall survival figures, so they also include women who die of other causes. The numbers are approximate and come from women treated more than 10 years ago.

Stage/5-Year Survival Rate
  • IA: Above 95%
  • IB1: Around 90%
  • IB2: Around 80%-85%
  • IIA/B: Around 75%-78%
  • IIIA/B: Around 47%-50%
  • IV: Around 20%-30%

How is Cervical Cancer Treated?
  • Surgery
  • Radiation Therapy
  • Chemotherapy ***

Chemotherapy ***

For some stages of cervical cancer, chemotherapy is given to help the radiation work better. When chemotherapy and radiation therapy are given together, it is called concurrent chemoradiation. One option is to give a dose of cisplatin every week during radiation. This drug is given into a vein (IV) about 4 hours before the radiation appointment. Another choice is to give cisplatin along with fluorouracil (5-FU) every 4 weeks during radiation. Other drug combinations are also used. Giving chemotherapy with radiation can improve the patient’s prognosis, but they may have more side effects. Many women notice feeling more nausea and fatigue. Diarrhea may be a problem if chemotherapy is given at the same time as radiation. Problems with low blood counts can also be worse. Your health care team will watch for side effects and can give you medicines to help you feel better.

Systemic chemotherapy uses anticancer drugs that are injected into a vein or given by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment potentially useful for cancers that have spread to distant organs (metastasised).

Drugs most often used to treat cervical cancer include cisplatin, paclitaxel, topotecan, ifosfamide, and fluorouracil. If chemotherapy is chosen, patient may receive a combination of drugs. Chemotherapy drugs kill cancer cells but also damage some normal cells, which can lead to side effects.

Chemotherapy side effects depend on the type of drugs, the amount taken, and the length of time you are treated. Temporary side effects of chemotherapy might include:
  • nausea and vomiting
  • loss of appetite
  • loss of hair
  • mouth sores
Because chemotherapy can damage the blood-producing cells of the bone marrow, the blood cell counts might become low. This can result in:
  • an increased chance of infection (due to a shortage of white blood cells)
  • bleeding or bruising after minor cuts or injuries (due to a shortage of blood platelets)
  • shortness of breath (due to low red blood cell counts)

Fatigue is also quite common and may be caused by low red blood cell counts, by other reasons related to the chemotherapy, or by the cancer itself.

Most side effects of chemotherapy (except premature menopause and infertility) disappear once treatment is stopped. Hair will grow back after treatment ends. Premature menopause can be treated with hormones.

If patient have problems with side effects, talk with cancer care team. There are remedies for many of the temporary side effects of chemotherapy. For example, there are very good drugs that can prevent or reduce nausea and vomiting. Other drugs can be given to boost blood cell production.

For some stages of cervical cancer, chemotherapy is given to help the radiation work better. When chemotherapy and radiation therapy are given together, it is called concurrent chemoradiation. One option is to give a dose of cisplatin every week during radiation. This drug is given into a vein (IV) about 4 hours before the radiation appointment. Another choice is to give cisplatin along with fluorouracil (5-FU) every 4 weeks during radiation. Other drug combinations are also used. Giving chemotherapy with radiation can improve the patient’s prognosis, but they may have more side effects. Many women notice feeling more nausea and fatigue. Diarrhea may be a problem if chemotherapy is given at the same time as radiation. Problems with low blood counts can also be worse. Your health care team will watch for side effects and can give you medicines to help you feel better.

Clinical trials

Treatment Options by Stage

The stage of a cervical cancer is the most important factor in choosing treatment. However, other factors that affect this decision include the exact location of the cancer within the cervix, the type of cancer (squamous cell or adenocarcinoma), your age, your overall physical condition, and whether you want to have children.

Stage 0 (carcinoma in situ)

Treatment options are the same as for pre-cancerous changes (dysplasia or cervical intraepithelial neoplasia [CIN]). Options include cryosurgery, laser surgery, loop electrosurgical excision procedure (LEEP/LEETZ), and cold knife conisation.

A simple hysterectomy is also an option for treatment, and may be done if the cancer returns. All of these cancers can be cured with appropriate treatment. However, pre-cancerous changes or stage 0 cancer can recur (come back) in the cervix or vagina, so it is very important for doctor to watch patient closely.

Stage I

Stage IA is divided into stage IA1 and stage IA2

Stage IA1: For this stage you have 3 options

  • If patient still want to be able to have children, first the cancer is removed with a cone biopsy, and then patient are watched closely to see if the cancer comes back.
  • If the cone biopsy doesn't remove all of the cancer (or if patient are done having children), the uterus will be removed (simple hysterectomy).
  • If the cancer has invaded the blood vessels or lymph vessels, patient will need a radical hysterectomy along with removal of the pelvic lymph nodes.

Stage IA2: There are 3 treatment options

  • radical hysterectomy along with removal of lymph nodes in the pelvis.
  • external beam radiation therapy plus brachytherapy.
  • radical trachelectomy with removal of pelvic lymph nodes can be done if the patient still wants to be able to have children.

If patient have surgery, the tissue removed is examined in the laboratory to see if the cancer has spread further than expected. If the cancer has spread to the tissues next to the uterus (called the parametria) or to any lymph nodes, radiation therapy is usually recommended. Often chemotherapy will be given with the radiation therapy. If the pathology report says that the tumour had positive margins, this means that some cancer may have been left behind. This is also treated with pelvic radiation (given with cisplatin chemotherapy). The doctor may advise brachytherapy, as well.

Stage IB is divided into stage IB1 and stage IB2

Stage IB1: Either of 3 treatments may be used if patient have stage IB1 cervical cancer.

  • The first option is a radical hysterectomy with removal of lymph nodes in the pelvis. Some lymph nodes from higher up in the abdomen (called para-aortic lymph nodes) are also removed to see if the cancer has spread there. If cancer cells are found in the edges of the organs removed (positive margins) or if cancer cells are found in lymph nodes during this operation, radiation therapy may be given, possibly with chemotherapy, after surgery.
  • The second treatment option is high-dose internal and external radiation therapy.
  • Radical trachelectomy with removal of pelvic (and some para-aortic) lymph nodes is an option if the patient still wants to be able to have children.

Stage IB2

  • The standard treatment is the combination of chemotherapy with cisplatin and radiation therapy to the pelvis plus brachytherapy.
  • Another choice is radical hysterectomy with removal of pelvic (and some para-aortic) lymph nodes. If cancer cells are found in the lymph nodes removed, or in the margins, radiation therapy may be given, possibly with chemotherapy, after surgery.
  • Some doctors advise radiation given with chemotherapy (first option) followed by a hysterectomy.

Stage II

Stage IIA: Treatment for this stage depends on the size of the tumor..

  • One choice for treatment is brachytherapy and external radiation therapy. This is most often recommended if the tumor is larger than 4 cm (about 1½ inches). Chemotherapy with cisplatin will be given along with the radiation.
  • Some experts recommend removing the uterus after the radiation therapy is done.
  • If the cancer is not larger than 4 cm, then the treatment may be radical hysterectomy and removal of lymph nodes in the pelvis (and some in the para-aortic area). If the tissue removed at surgery shows cancer cells in the margins or cancer in the lymph nodes, treatment will include radiation treatments given with chemotherapy. Brachytherapy may be given as well.
Stage IIB: Combined internal and external radiation therapy is the usual treatment. The radiation is given with the chemotherapy drug cisplatin. Sometimes other chemo drugs may be given along with cisplatin.

Stage III and IVA

Combined internal and external radiation therapy given with cisplatin is the recommended treatment.

If cancer has spread to the lymph nodes (especially those in the upper part of the abdomen) it can be a sign that the cancer has spread to other areas in the body. Some experts recommend checking the lymph nodes for cancer before giving radiation. One way to do this is by surgery. Another way is to do a CT or MRI scan to see how big the lymph nodes are. Lymph nodes that are bigger than usual are more likely to have cancer. Those lymph nodes can be biopsied to see if they contain cancer. If lymph nodes in the upper part of the abdomen (the para-aortic lymph nodes) are cancerous, doctors may want to do other tests to see if the cancer has spread to other parts of the body.

Stage IVB

At this stage, the cancer has spread out of the pelvis to other areas of the body. Stage IVB cervical cancer is not usually considered curable. Treatment options include radiation therapy to relieve the symptoms of cancer that has spread locally (near the cervix) or distant metastases. Chemotherapy is often recommended. Most standard regimens use a platinum compound, either cisplatin or carboplatin along with another drug such as paclitaxel, gemcitabine, topotecan, or vinorelbine. Clinical trials are testing other combinations of chemotherapy drugs, as well as some other experimental treatments.

Recurrent cervical cancer

Cancer is called recurrent when it come backs after treatment. Cancer can come back locally (in the pelvic organs near the cervix) or come back in distant areas (spread through the lymphatic system and/or the bloodstream to organs such as the lungs or bone).

If the cancer has recurred in the pelvis only, extensive surgery (by pelvic exenteration) may be an option for some patients. This operation may successfully treat 40% to 50% of patients. Sometimes radiation or chemotherapy may be used for palliative treatment (treatment to relieve symptoms but not expected to cure).

If patient's cancer has recurred in a distant area chemotherapy or radiation therapy may be used to treat and relieve specific symptoms. If chemotherapy is used, patient should understand the goals and limitations of this therapy. Sometimes chemotherapy can improve quality of life, and other times it can diminish it. Patient needs to discuss this with doctors. Fifteen percent to 25% of patients may respond at least temporarily to chemotherapy.

New treatments that may benefit patients with distant recurrence of cervical cancer are being evaluated in clinical trials. Patient may want to think about participating in a clinical trial.




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