TREATMENT, SYMPTOMS AND CAUSES OF CERVICAL CANCER

Cervical cancer, or cancer of the cervix, is cancer of the entrance to the uterus (womb). The cervix is the narrow part of the lower uterus, often referred to as the neck of the womb. Cervical cancer occurs most commonly in women over the age of 30.

The American Cancer Society estimates that 12,900 diagnoses of cervical cancer will be made by the end of 2015 in the USA. Over 4,000 women in the USA die from cervical cancer each year.

The National Health Service (NHS), UK, says that over 3,000 women are diagnosed with cervical cancer each year in the UK. According to the World Health Organization (WHO) at least 200,000 women worldwide die of cervical cancer each year. WHO adds that if the HPV vaccine is administered globally, hundreds of thousands of lives each year could eventually be saved.

Cancer research UK reported that the rate of women diagnosed with the cervical cancer in the UK has halved from 16 per 100,000 in 1988 to 8 per 100,000 - the NHS (National Health Service) Cervical Screening Programme began in 1988. 

Fast facts on cervical cancer

Here are some key points about cervical cancer. More detail and supporting information is in the main article.

• There are two main types of cervical cancer: squamous cell cervical cancer and adenocarcinoma of the cervix.
• Cervical cells are most likely to become cancerous in the transformation zone, found at the opening of the cervix.
• Women can be asymptomatic during the early stages of cervical cancer.
• Cervical cancer risk factors include smoking, giving birth at a young age and having a weakened immune system.
• Experts state that cervical cancer screening should not occur more than once every 3-5 years.
• It is estimated that the majority of cervical cancer deaths would be prevented if all women underwent cervical cancer screening.
• Cervical cancer screening should begin from the age of 21, or within three years of the first sexual encounter.
• Like all cancers, there are various stages of severity to cervical cancer, numbered from 0-4.
• Treatment for cancer that is confined to the cervix has a high rate of success - around 80%-95%.
• Cervical cancer risk can be reduced through various measures, including the human papillomavirus vaccine and practicing safe sex.

What is the cervix?

The cervix is part of the female reproductive system and is often referred to as the neck of the womb.

The cervix, or the neck of the womb, and the womb are both parts of a female reproductive system. The female reproductive system consists of:

• Vagina
• Womb (uterus), which includes the cervix
• Ovaries.

Women have two ovaries, one on either side of the lower abdomen (pelvis). Each month one of the ovaries produces an egg. Each ovary is connected to the uterus by a tube called the Fallopian tube.

In between each menstrual period an egg travels down one of the fallopian tubes and into the uterus. They alternate - one month may be the left side, and the next month the right side. When the egg enters the womb its lining thickens in preparation; in case the egg is fertilized by a man's sperm. If fertilization does not occur the thickened lining of the uterus is shed - a period (menses) occurs.

The cervix is the opening from the uterus to the vagina. It is a tight muscle that is normally firmly shut, with a small opening to allow the sperm through and the flow from a menstrual period. During labor (childbirth) the cervix opens.

Types of cervical cancer

Ectocervix - flat cells - squamous cell cervical cancer

The ectocervix is the portion of the cervix that projects into the vagina, also known and the portio vaginalis. It is about 3 cm long and 2.5 cm wide. There are flat cells on the outer surface of the ectocervix. These fish scale-like cells can become cancerous, leading to squamous cell cervical cancer.
Squamous cells - flat cells that look like fish scales. The word comes from Latin "squama" meaning "the scale of a fish or serpent". Our outer-layer skin cells are squamous cells, as well as the passages of the respiratory and digestive tracts, and the linings of hollow internal organs.

Endocervix - glandular cells - adenocarcinoma of the cervix

The endocervix is the inside of the cervix. There are glandular cells lining the endocervix; these cells produce mucus. These glandular cells can become cancerous, leading to adenocarcinoma of the cervix.
Adenocarcinoma - any cancer that develops in the lining or inner surface of an organ.

Transformation zone

This is where cervical cells are most likely to become cancerous. The transformation zone is located around the opening of the cervix, leading on to the endocervical canal (narrow passageway running up the cervix into the uterus). During cervical screening doctors and nurses will focus on this area.

Causes of cervical cancer

Cancer is the result of the uncontrolled division of abnormal cells. Most of the cells in our body have a set lifespan; when they die new cells are produced to replace them. Abnormal cells can have two problems:

1. They do not die
2. They continue dividing.

This results in an excessive accumulation of cells which eventually form a lump - a tumor. Scientists are not completely sure why cells become cancerous. However, there are some risk factors which are known to increase the risk of developing cervical cancer. These risk factors include:

HPV (human papilloma virus)

Around 70% of cervical cancer cases are estimated to be caused by HPV.

Human papilloma virus infection is a sexually transmitted virus. There are over 100 different types of HPVs - 15 types can cause cervical cancer; probably 99% of them. In addition there are a number of types which can cause genital warts. It is estimated that HPV types 16 and 18 cause about 70% of cases cervical cancer while HPV types 6 and 11 cause 90% of genital warts.

Other HPV types can cause cervical intra-epithelial neoplasia (CIN) - the growth of abnormal cells on the surface of the cervix.

Many sexual partners, becoming sexually active early

Cervical cancer-causing HPV types are nearly always transmitted as a result of sexual contact with an infected individual. Women who have had many sexual partners generally have a higher risk of becoming infected with HPV, which raises their risk of developing cervical cancer. There is also a link between becoming sexually active at a young age and a higher risk of cervical cancer.

If a woman develops cervical cancer it does not mean she had several sexual partners, or became sexually active earlier than most other females. It is just a risk factor. Women who only ever had one sexual partner can develop cervical cancer.

Smoking

Smoking increases the risk of developing many cancers, including cervical cancer.

Weakened immune system

People with weakened immune systems, such as those with HIV/AIDS, or transplant recipients taking immunosuppressive medications have a higher risk of developing cervical cancer.

Certain genetic factors

Scientists at Albert Einstein College of Medicine of Yeshiva University found that women with certain gene variations appear to be protected against cervical cancer.

Long-term mental stress

A woman who experiences high levels of stress over a sustained period may be undermining her ability to fight off HPV and be at increased risk of developing cervical cancer it can cause, scientists at the Fox Chase Cancer Center reported.

Giving birth at a very young age

Women who gave birth before the age of 17 are significantly more likely to develop cervical cancer compared to women who had their first baby when they were aged 25 or over.

Several pregnancies

Women who have had at least three children in separate pregnancies are more likely to develop cervical cancer compared to women who never had children.

Contraceptive pill

Long-term use of some common contraceptive pills slightly raises a woman's risk.

Other sexually transmitted diseases (STD)

Women who become infected with chlamydia, gonorrhea, or syphilis have a higher risk of developing cervical cancer. Scientists at the Medical University of South Carolina found that HPV infections last longer if Chlamydia also is present.

Socio-economic status

Studies in several countries have revealed that women in deprived areas have significantly higher rates of cervical cancer, compared to women who live in other areas. Studies have also found higher rates in women of working age in manual jobs, compared to women in non-manual jobs. The most likely reason is a difference in the proportion of women who have regular screening. Scientists at King's College London found that some areas in South East England had rates that were three times higher than neighboring areas.

Recent developments on cervical cancer causes from MNT news
Oral HPV 'can be transmitted by oral-to-oral, oral-to-genital routes'
A new study claims to provide further evidence that oral human papillomavirus infections can be transmitted via oral-to-oral and oral-to-genital routes.
Two thirds of healthy American adults 'infected with HPV,' study suggests
In what has been deemed the "largest and most detailed genetic analysis of its kind," researchers have discovered that two thirds of healthy American adults may be infected with one or more of 109 strains of human papillomavirus.

Symptoms of cervical cancer

Often during the early stages people may experience no symptoms at all. That is why women should have regular cervical smear tests.

The most common symptoms are:

• Bleeding between periods
• Bleeding after sexual intercourse
• Bleeding in post-menopausal women
• Discomfort during sexual intercourse
• Smelly vaginal discharge
• Vaginal discharge tinged with blood
• Pelvic pain.

Diagnosis and Stages

Tests and diagnosis

The earlier cervical cancer is diagnosed the more successfully it can be treated. Regular cervical screening can save thousands of live every year.

Cervical cancer screening should occur no more than once every three to five years, the American College of Obstetricians and Gynecologists announced on 23rd October, 2012. They added that the PAP test should be carried out at the same time as the HPV test - testing for both is better than just the PAP test alone. The College emphasized that this recommendation is just for women aged 30 years or more. Their guidelines were published in Obstetrics & Gynecology.

Cervical screening - LBC or Pap smear test

In the USA over 11,000 women are diagnosed with invasive cervical cancer each year and about 4,000 die of it. The majority of these deaths could be prevented if all women had undergone cervical screening. US authorities say a female should start screening at the age of 21, or within three years of her first sexual encounter - whichever occurs first.

The test looks for abnormal changes in the cells of the cervix. If left untreated some abnormal cells can eventually develop into cancer. Cervical screening does not detect cancer.

Experts believe that the majority of deaths from cervical cancer would be prevented if all women underwent cervical screening as recommended.

Cervical screening used to be the old pap smear test - which is still used in many parts of the world. More recently, testing using LBC (liquid based cytology) has become more commonplace. A sample of cells is taken from the cervix. The doctor or nurse inserts a speculum - an instrument used to widen the opening of the vagina so that the cervix is more easily visible - and uses a spatula which is brushed around the cervix. The procedure is just mildly uncomfortable for the majority of women. If abnormal cells are there, there is a good chance they will be detected, but not not always.

What is LBC (liquid based cytology)?

Cytology is the medical and scientific study of cells - diagnosing diseases and conditions by examining tissue samples (cell samples) from the body. With liquid based cytology the sample is collected in much the same way as a conventional smear. However, instead of smearing the sample onto a microscope slide, the head of the brush where the sample cells are caught is broken off and placed in a small glass vial which contains preservative fluid - sometimes it can be rinsed directly into the preservative fluid. In the laboratory it is spun and treated to remove mucus, pus and other materials. A random sample of the remaining cells is taken. A thin layer of the cells is placed on a microscope slide and examined.

The test is not designed for diagnosing cancer. It is designed to check the health of the cervix and to detect early changes in the cells, which could develop into cancer in the future.

The best time to have the test is in the middle of the menstrual cycle - between periods.

If the test results show abnormal cells in the cervix the doctor will refer the patient to a gynecologist. In the UK the patient may also be referred to a nurse colposcopist.

HPV DNA test

Also known as just "HPV test". This test determines whether the patient is infected with any of the HPV types that are most likely to cause cervical cancer. This involves collecting cells from the cervix for lab testing. The test can detect high risk HPV strains in cell DNA before any cervix cell abnormalities appear. A British study found that the combination of HPV testing with regular liquid-based cytology (LBC) screening does not improve the detection of cervical cancer compared with LBC screening alone. An eight-year trial involving more than 130,000 women published in The New England Journal of Medicine found that that in low-resource settings a single round of HPV testing significantly reduces the numbers of advanced cervical cancers and deaths, compared with Pap (cytology) testing.

If the patient experiences signs and symptoms of cervical cancer, or if the Pap test revealed abnormal cells, the patient may undergo additional tests:

Biopsy

A small piece of tissue will be taken. The patient will be anesthetized for this.

Colposcopy

This is performed in the doctor's office. A speculum is placed to hold the vagina open and the gynecologist looks at the cervix through a colposcope - a lighted magnifying instrument specifically designed for examining the tissues of the vagina and the cervix. If the doctor is still unable to see the abnormal area clearly a cone biopsy or LETTZ may be done.

Cone biopsy

A small cone-shaped section of the abnormal tissue is taken from the cervix for examination under a microscope. The patient is usually under local anesthetic; sometimes general anesthetic is used. The biopsy may indicate whether the abnormal cells are CIN 1, 2 or 3, or whether deeper levels of the cervix are affected.

LLETZ

A diathermy (wire loop with an electric current) is used to remove abnormal tissue. The tissue is sent to the lab to be checked. This is a common treatment for CIN.

Blood tests

A blood test will reveal the number of blood cells, as well as identifying any liver or kidney problems.

Chest X-ray

This is to determine the health of the patient's lungs and heart.

Examination under anesthetic (EUA)

This allows the doctor to examine the vagina and cervix more thoroughly. The patient is under a general anesthetic. The doctor may also check the bladder with a cystoscope, or/and the colon and rectum with a procto-sigmoidoscope to determine whether the cancer has spread. During this whole procedure the doctor may take a biopsy of the bladder, colon/rectum and the lining of the uterus.

CT (computerized tomography) scan

A CT scanner emits a series of narrow beams through the human body as it moves through an arc, unlike an X-ray machine which sends just one radiation beam. The final picture is far more detailed than an X-ray one. Inside the CT scanner there is an X-ray detector which can see hundreds of different levels of density. It can see tissues inside a solid organ. This data is transmitted to a computer, which builds up a 3-D cross-sectional picture of the part of the body and displays it on the screen. The doctor will have a much better idea of the size and position of the cancer.

The patient will have to have a barium drink beforehand. The barium appears white on the scan. Just before the scan a tampon may be placed into the vagina, and a barium liquid may be placed into the rectum. The whole scan takes from 10 to 30 minutes.

MRI (magnetic resonance imaging scan)

An MRI does not use X-rays; it uses magnets and radio waves to build up cross-sectional images of the targeted part of the body. The patient lies very still on a couch inside a long tube which enters a doughnut-like machine. As the machine can become noise patients will usually be given earphones so that they can listen to music - some may even let you bring your own tunes. All metal items should be removed beforehand because the MRI machine is a powerful magnet. If you have any metal in your body, such as a pacemaker or surgical clips you cannot have an MRI scan. By using high-MRI with a special vaginal coil, a technique to measure the movement of water within tissue, researchers may be able to identify cervical cancer in its early stages, researchers at Cancer Research UK Clinical Magnetic Resonance Research Group reported.

Pelvic ultrasound

This is a device that uses high frequency sound waves which create an image on a monitor of the target area. The patient will be asked to drink plenty of fluids beforehand so that the bladder is full and a clear picture can be viewed. A transvaginal ultrasound device may be inserted into the vagina, or an external device may be placed next to the stomach.

Pretreatment MRI and PET/CT for cervical cancer may direct more women to optimal therapy choices and spare many women potential long-term morbidity and complications of trimodality therapy (surgery followed by chemoradiation), according to a study performed at the Institute for Technology Assessment in Boston.

The stages of cervical cancer

After carrying out the various tests the doctor will determine the stage of the cancer. The stage of a cancer refers to how far it has spread. Determining the stage of the cancer is important because it is the main factor in deciding on treatment options. Cancers have various staging systems. In cervical cancer, stages are numbered from 0 to 4. If you have CIN it means you have abnormal cells, it is not the same as cervical cancer and the stages below do not apply, except for perhaps stage 0. 

 

Stage 0 - Carcinoma in situ (stage 0)

Even though there are only abnormal cells on the surface layer of the cervix and this is not considered to be part of the cervical cancer staging system, many doctors will call this Stage 0. It is not an invasive cancer; the cells have not left the area where they started to grow. This is the same as CIN 3.

Stage 1 cervical cancer

The cancer is only in the cervix (the neck of the uterus, womb). This stage is divided into:

• Stage 1A - cancer is microscopic; it can only be viewed through a microscope. This stage is divided into two:
  1A1 - cancer has grown into less than 3 mm of the cervical tissue, and is less than 7mm wide
  1A2 - cancer has grown 3-5mm into cervical tissue, and is less than 7mm wide.
• Stage 1B - cancer is larger and is usually visible with the naked eye, but is confined to the cervical tissue and has not spread. This stage is divided into two:
  1B1 - cancer is no larger than 4cm
  1B2 - cancer is larger than 4cm.

This stage of cervical cancer is generally treated with surgery or radiotherapy. For patients at Stage 1B2 a combination of chemotherapy and radiotherapy may be recommended sometimes.

Stage 2 cervical cancer

The cancer includes the cervix and uterus, but has not yet spread into the pelvic wall or lower portions of the vagina. It is divided into two stages:

• Stage 2A - the cancer has reached the top of the vagina
• Stage 2B - the cancer has reached tissue around the cervix.

Treatment for Stage 2A usually consists of surgery or radiotherapy, and sometimes both. Treatment for Stage 2B invariably consists of a combination of radiotherapy and chemotherapy.

Stage 3 cervical cancer

The cancer has spread beyond the cervix and uterus and has reached the surrounding structures of the pelvic area, the lower portion of the vagina, and the pelvic wall (muscles and ligaments that line the pelvis). The cancer growth may have blocked the ureter (the tube that carries urine from the kidneys to the bladder). It is divided into two stages:

• Stage 3A - the cancer has reached the lower third of the vagina, but not the pelvic wall
• Stage 3B - the cancer has grown through the pelvic wall, or is blocking one ureter or both of them.

The most common treatment option for this stage is a combination of chemotherapy and radiotherapy.

Stage 4 cervical cancer

Advanced cancer; the cancer has spread to nearby organs, such as the bladder or rectum, or it has spread further into other parts of the body, such as the liver, lungs or bones. This is divided into two stages:

• Stage 4A - the cancer has reached the bladder or rectum (nearby organs)
• Stage 4B - the cancer has spread further, possibly including the lungs, liver or bones.

Treatments for cervical cancer

It is important to ask questions about any aspects of your treatment that you are not sure about, or anything that worries you.

Talking about the benefits and disadvantages of various options with an expert, such as a gynecologist, gynecological nurse or your GP (general practitioner, primary care physician) will help you understand the process. Some people find it useful to write down a list of questions, while others appreciate the company and support of a relative or close friend when they go to the doctor.

Cancer treatments can sometimes be complex and bewildering and not that straightforward for lay people to figure out. Doctors and health care professionals are used to people asking questions, and they should also be used to and should not mind explaining things again and again. Even if you worry that the hospital staff may be too busy to answer your questions, they should be eager to answer your them thoroughly so that you know how the therapies may possibly affect you.

Cervical cancer treatment options include surgery, radiotherapy, chemotherapy, or combinations. Deciding on the kind of treatment depends on several factors, such as the stage of the cancer, as well as the patient's age and general state of health.

Treatment for early stage cervical cancer - cancer that is confined to the cervix - has a success rate of 85% to 90%. The further the cancer has spread out of the area it originated from, the lower the success rate tends to be.

Early stage cancer treatment options

Surgery is commonly used when the cancer is confined to the cervix. Radiotherapy may be used after surgery if the doctor believes there may still be cancer cells inside the body. Radiotherapy may also be used to reduce the risk of recurrence (cancer coming back). If the surgeon wants to shrink the tumor in order to make it easier to operate, the patient may receive chemotherapy - however, this is not so common.

The options for surgery in the early stages may include:

• Cone biopsy (conization) - this procedure may also be used to remove any abnormality. The surgeon uses a scalpel to remove a cone-shaped piece of cervical tissue
• Laser surgery - a narrow beam of intense light destroys cancerous and precancerous cells
• LEEP (loop electrosurgical excision procedure) - a wire loop which has an electric current cuts through tissue removing cells from the mouth of the cervix
• Cryosurgery - cancerous and precancerous cells are destroyed by freezing them
• Hysterectomy - the cancerous and precancerous areas, as well as the cervix and the uterus are surgically removed. This is not common and is only done in certain cases of noninvasive cervical cancer.

Advanced cancer

When the cancer has spread beyond the cervix surgery is not usually an option. Advanced cancer is also referred to as invasive cancer because it has invaded other areas, not just where it started off. This type of cancer requires more extensive treatment. The patient will typically be treated with either radiotherapy or a combination of radiotherapy and chemotherapy. In the later stages of cancer palliative therapy is administered to relieve symptoms and improve quality of life.

Radiotherapy

Radiotherapy is commonly used to treat advanced forms of cervical cancer. Around 40% of all cancer patients undergo some form of radiotherapy.

Radiotherapy is also known as radiation therapy, radiation oncology and XRT. It is used for treating cancer, thyroid disorders and some blood disorders. Approximately 40% of cancer patients undergo some kind of radiotherapy. It involves the use of beams of high-energy X-rays or particles (radiation) to destroy cancer cells. Radiotherapy works by damaging the DNA inside the tumor cells, destroying their ability to reproduce.

This may be delivered externally or internally (brachytherapy) by placing radioactive material near the cervix. For patients with advanced cervical cancer radiation combined cisplatin-based chemotherapy is the most effective treatment, according to gynecologic oncologists.

Radiation that is aimed in the pelvic area may cause the following side effects; some of them may not emerge until well after the treatment is over:

• Diarrhea
• Nausea
• Upset stomach
• Bladder irritation
• Narrowing of the vagina
• Interrupted menstrual cycle
• Early menopause.

Chemotherapy

Chemotherapy is the use of chemicals (medication) to treat any disease - more specifically in this text, it refers to the destruction of cancer cells. Cytotoxic medication prevents cancer cells from dividing and growing. When health care professionals talk about chemotherapy today, they tend to refer more to cytotoxic medication than others. Chemotherapy for cervical cancer, as well as most other cancers, is used to target cancer cells that surgery cannot or did not remove, or to help the symptoms of patients with advanced cancer.

Cisplatin, a chemotherapy drug, is frequently used in combination with radiotherapy.

Side effects of chemotherapy may vary, and depend a lot on the specific drug being used. Below is a list of the more common side effects:

• Diarrhea
• Nausea
• Hair loss
• Fatigue
• Infertility
• Early menopause.

Clinical trials

For some patients, participating in a clinical trial may be their best treatment option. Many current treatments are the results of clinical trials. Clinical trials are an integral part of the cancer research process. A clinical trial is carried out to determine how safe and effective new treatments are, and whether they are better than existing ones.

A participant in a clinical trial may either receive the standard treatment, or the new treatment. A clinical trial compares a number of patients on the new treatment to a group of patients on an existing treatment. Sometimes a clinical trial may also have a group of patients taking a placebo (dummy drug).

Clinical trial participants contribute to cancer research and innovation.

Recent developments on cervical cancer treatment from MNT news
Targeted drug 'prolongs survival for cervical cancer patients'
The American Cancer Society estimate that there will be 12,360 new cases of invasive cervical cancer diagnosed this year, with 4,020 deaths from the disease. Now, a phase II trial has found that a targeted antitumor drug could prolong the survival of women with cervical cancer.
Avastin Can Lengthen The Lives Of Advanced Cervical Cancer Patients
The addition of targeted therapy Avastin (bevacizumab) with chemotherapy can significantly lengthen the lives of women with advanced cervical cancer by close to 30%, according to research presented at the 2013 American Society of Clinical Oncology Congress.
Just one HPV vaccine dose 'could be enough' to prevent cervical cancer
The need for numerous doses of the HPV vaccine has been called into question by researchers who say that a one-dose schedule could be sufficient and should be investigated for the protection of most women against cervical cancer.
The suggestion comes from the authors of a new analysis to combine data from two large phase 3 trials that has been published in The Lancet Oncology.

Prevention of cervical cancer

There are a number of measures that can be taken to reduce the chances of developing cervical cancer.

HPV (human papilloma virus) vaccine

The link between the development of cervical cancer and some types of HPV is clear. At least 70% of all cases of cervical cancer occur because of 2 types of HPVs for which there is a vaccine. If every female adheres to current HPV vaccination programs the total number of female deaths from cervical cancer globally will drop by hundreds of thousands each year.

Public health authorities in most countries now offer the HPV vaccine as part of their childhood immunization program. UK authorities say girls should be given the vaccine when they are 12 to 13 years of age - in three doses over a six month period.

Safe sex

The HPV vaccine only protects against two HPV strains. There are others which can cause cervical cancer. Using a condom during sex helps protect from HPV infection. HPV is a sexually transmitted infection.

Cervical screening

Regular cervical screening will make it much more likely that signs are picked up early on and dealt with before cancer develops at all or too far.

Have few sexual partners

The more sexual partners a woman has the higher is her risk of developing cervical cancer.

Delay first sexual intercourse

The younger a female is when she has her first sexual intercourse the higher is her risk of developing cervical cancer. The longer she delays it, the lower her risk.

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