Cervical Cancer – Definition, Causes, and Treatment.

Definition

Cervical cancer starts in the cells of the cervix. The cervix is the narrow, lower part of the uterus (or womb). It is the passageway that connects the uterus to the vagina. Before cervical cancer develops, the cells of the cervix start to change and become abnormal. Growths on the cervix can be benign (not cancer) or malignant (cancer). These abnormal cells are precancerous, meaning that they are not cancer.

Precancerous changes to the cervix are called dysplasia of the cervix (or cervical dysplasia). Dysplasia of the cervix is not cancer. It is a common precancerous change that can develop into cancer over time if it’s not treated. It’s important to know that most women with dysplasia do not develop cancer. Cervical cancer is almost always caused by a human papillomavirus (HPV) infection.

Structure of Cervix and the cancer affected area

The cervix

The cervix is part of a woman’s reproductive system. It’s in the pelvis. The cervix is the lower, narrow part of the uterus (womb).

The cervix is a passageway:

• The cervix connects the uterus to the vagina. During a menstrual period, blood flows from the uterus through the cervix into the vagina. The vagina leads to the outside of the body.
• The cervix makes mucus. During sex, mucus helps sperm move from the vagina through the cervix into the uterus.
• During pregnancy, the cervix is tightly closed to help keep the baby inside the uterus. During childbirth, the cervix opens to allow the baby to pass through the vagina.

Historical background of cervical cancer

Dr Georges Papanicolaou’s screening method (the Pap smear) started in the US in the 1940s. It was widely used in the UK a decade later and a national programme of cervical screening was established in 1988. The association of sexually transmitted human papillomavirus (HPV) with cervical cancer was less readily accepted. The detection of HPV16 in cervical cancers at the end of the 1970s was aided by the explosion of laboratory, clinical, and public health research on new screening tests and procedures. These made possible the successful development, licensing and use of preventive vaccines against the major oncogenic HPV types, HPV16 and -18.

Epidemiology

Cervical cancer is the third most frequent cancer in women. In Europe, 10.6 women in 100,000 were diagnosed with cervical cancer in 2008. This is about 4% of all cancers diagnosed in women. Nearly 1% of all women develop cervical cancer over their lifetime in Europe.

Given the fact that a vaccine protecting against the most frequent types of human papilloma virus (HPV) involved in cervical cancer is now available, cervical cancer will likely become less frequent in the future.

The risk for cervical cancer is higher in Eastern Europe (especially in Serbia, Romania, Bulgaria and Lithuania) because of the lack of organised population-based screening programmes. Unfortunately, the situation is much bleaker in developing countries, where 85% of new cases occur.

Because of the frequent inaccessibility of screening and treatments the mortality rate is 10 times higher in developing countries than in developed countries. Moreover, presently, the cost of the prevention vaccination is such that it will likely remain unavailable for most women in many parts of the world.

Causes

• It has become clear that essentially all cervical cancers are caused by certain types of the human papilloma virus (HPV), a group of viruses akin to the virus that causes skin or genital warts.
• Infection with HPV is caused by direct contact and in the case of the cervix is usually aroused by sexual contact or even by skin-to-skin contact.

Risk factors for being infected with HPV

• Unprotected sexual intercourse with multiple partners or sexual intercourse with a man who has multiple sex partners.
• Onset of sexual intercourse activity at an early age.
• Long-term use of hormonal contraceptives.
• Multiple pregnancies.
• Poor hygiene.
• Other sexually transmitted genital infections, e.g. Chlamydia trachomatis and herpes simplex virus-2.
• Having HIV (the virus that causes AIDS) or another condition that makes it hard for your body to fight off health problems.
• Using birth control pills for a long time (five or more years).
• Having given birth to three or more children.

Symptoms of Cervical cancer

The most common signs and symptoms of cervical cancer include:

• Abnormal bleeding from the vagina bleeding or spotting between regular menstrual periods
• Bleeding after sex
• Bleeding after douching menstrual periods that last longer or are heavier than before
• Bleeding after menopause
• Pain during sex
• More vaginal discharge than normal

How is cervical cancer diagnosed?

Cervical cancer must be suspected in the following circumstances:

• Abnormalities upon gynaecological examination*.
• Severe abnormalities in cervical smears.
• Bleeding outside of menstruation periods.
• Bleeding after sexual intercourse.

The diagnosis of cervical cancer is based on the following examinations.

1. Clinical examination

• This includes gynaecological examination by bimanual rectal vaginal examination* to assess the location and volume of the tumor and whether it has extended to other organs in the pelvis.
• The doctor directly visualises the cervix after inserting a speculum into vagina.
• The doctor takes a smear of the surface of the cervix to be examined under the microscope (cytological examination). This examination can be done under anesthesia.

2. The Pap smear test

• Pre-cancerous cervical lesions may be present for many years without causing any symptoms.
• The cervix is palpable and visible upon gynaecological inspection so that the doctor can easily obtain smears from its surface for a cytological examination of the cells that are shed from the surface of the cervix, the so-called Pap smear or Pap test.

Pap test

• An abnormality of the cells of the cervical surface called dysplasia* which over the years might develop into a cancer. Also incipient cancer at this site is easily detected by smears before it becomes dangerous (malignant).
• Upon laboratory examination, the cells in the smear may:
• Be normal.
• Reveal mild dysplasia which is usually due to an infection caused by HPV. Other terms used to describe mild dysplasia are low-grade squamous intra-epithelial lesion (LSIL) and Cervical Intraepithelial Neoplasia of grade 1 (CIN 1).
• Mild dysplasia usually regresses spontaneously but can progress to a more severe stage of dysplasia.
• High-grade squamous intra-epithelial lesion (HSIL) and Cervical Intraepithelial Neoplasia of grade 2 or 3 (CIN 2/3). Such lesions could progress to cervical cancer if left untreated.
• Reveal a cancer of the cervix

3. Colposcopy

• Colposcopy is a procedure in which the patient lays on the exam table as during the pelvic exam. A speculum is placed in the vagina to help the doctor visualize the cervix.
• The doctor will use a colposcope to examine the cervix. A colposcope is an instrument that has magnifying lenses similar to binoculars. From outside the body it allows the doctor to see the cervix closely and clearly.

 

• The doctor applies a weak solution of acetic acid (like vinegar) to the cervix to make any abnormal areas easier to see. When an abnormal area is seen on the cervix, a biopsy is performed.

4. Histopathological examination

• This is usually performed after a suspicious Pap smear and during colposcopy in order to confirm the results of the Pap smear.
• It is the laboratory examination of the tumor tissue after removing a sample from the tumor (biopsy).
• This laboratory examination is performed by a pathologist who will confirm the diagnosis of cervical cancer and give more information on the characteristics of the pre-cancerous lesions (CIN 1 to 3) and cancer.
• The biopsy is obtained manually by the doctor with a special device introduced into the vagina during colposcopy.

5. Routine laboratory examination of blood and urine

• Blood and urine samples are taken for laboratory analysis to verify general health and diagnose possible undiagnosed problems such as anemia, liver or kidney malfunction, urinary infection, etc.

6. Medical imaging examinations

Medical imaging examinations are used to verify the extension of the tumor and exclude or detect eventual metastases.

• CT-scan and magnetic resonance imaging (MRI) are used to visualize any spread of the tumor to the pelvis and in the lymph nodes (located along the main vessels in the pelvis and along the aorta), which drain the tumor and can be sites of metastases
• Basic complementary examination includes chest X-ray. To examine the urinary system (including the ureter ducts between the kidneys and the bladder, which can be compressed by an expanding cervical cancer or lymph nodes) an intravenous pyelogram is performed (an X-ray visualization of the urinary system after intravenous injection of a contrast fluid.

Staging and grading

Once a definite diagnosis of cancer has been made, the cancer is given a stage and a grade. The cancer stage describes the tumour size and tells whether it has spread. For cervical cancer, there are 5 stages.

Stage	Description
0	Cancer is found only in the top layer of cells in the tissue that lines the cervix. Stage 0 is also called carcinoma in situ.
1	Cancer is found only in the cervix, beneath the top layer of cells.
2	Cancer has spread to nearby tissues such as the upper part of the vagina or tissues next to the cervix.
3	Cancer has spread to the lower part of the vagina or the pelvic wall or blocks the ureter (the tube that carries urine from a kidney to the bladder). It may also have spread to nearby lymph nodes.
4	The cancer has spread to the bladder, rectum or other distant parts of the body

 

A grade is given based on how the cancer cells look and behave compared with normal cells. To find out the grade of a tumour, the biopsy sample is examined under a microscope. There are 3 grades for cervical cancer.

Grade	Description
1	Low grade – slow-growing, less likely to spread.
2	Moderate grade.
3	High grade – tend to grow quickly, more likely to spread.

Treatment for cervical cancer

Surgery

• Surgery is an option for women with Stage I or II cervical cancer. You and your surgeon can talk about the types of surgery and which may be right for you.
• A decision to have surgery depends on the size and location of the tumour. During the operation, all or part of the tumour and some healthy tissue around the tumour are removed. Surgery is done under general anesthetic (you will be unconscious). You may stay in the hospital for several days or longer after the surgery.
• In other situations, it may be necessary to remove the entire uterus (an operation called a hysterectomy). Lymph nodes in the pelvis may also be removed during surgery. After a hysterectomy, you may have some pain, nausea or bladder and bowel problems.
• If you have surgery only on the surface of the cervix, you may have cramping, bleeding or vaginal discharge. These side effects are usually temporary.

Radiation therapy

• In external beam radiation therapy, a large machine is used to carefully aim a beam of radiation at the tumour. The radiation damages the cells in the path of the beam – normal cells as well as cancer cells.
• In brachytherapy, or internal radiation therapy, radioactive material is placed directly into or near the tumour.
• Radiation therapy may make your vagina narrower. There are ways to expand the vagina, which can help make follow-up exams easier. Radiation may also cause early menopause.
• For some stages of cervical cancer, the preferred treatment is radiation and chemo given together (called concurrent chemoradiation). The chemo helps the radiation work well. Options for concurrent chemoradiation include:
• Cisplatin given weekly during radiation. This drug is given into a vein (IV) about 4 hours before the radiation appointment.
• Cisplatin plus 5-fluorouracil (5-FU) given every 4 weeks during radiation.

Chemotherapy

• Chemotherapy uses drugs to treat cancer. Chemotherapy drugs may be given as pills or by injection (with a needle). They interfere with the ability of cancer cells to grow and spread, but they also damage healthy cells.
• Although healthy cells can recover over time, you may experience side effects from your treatment including nausea, vomiting, diarrhea, loss of appetite, fatigue (feeling extremely tired and lacking energy), hair loss and an increased risk of infection.
• The chemo drugs most often used to treat advanced cervical cancer include:
• Cisplatin
• Carboplatin
• Paclitaxel (Taxol),
• Topotecan
• Gemcitabine (Gemzar)
• Combinations of these drugs are often used. Some other drugs can be used as well, such as docetaxel (Taxotere), ifosfamide (Ifex), 5-fluorouracil (5-FU), irinotecan (Camptosar), and mitomycin.

Common side effects of chemotherapy can include:

• Nausea and vomiting
• Loss of appetite
• Loss of hair
• Mouth sores
• Fatigue (tiredness)

Biological therapy

Biological therapy (sometimes called immunotherapy) uses your immune system to fight cancer or to help control side effects of cancer treatments. Natural body substances or drugs made from natural body substances are used to boost your body’s own defences against illness.

Complementary therapies

Complementary therapies – for example, massage therapy or acupuncture – are used together with conventional cancer treatments, often to help ease tension and stress, as well as other side effects of treatment. They don’t treat the cancer itself.

Prevention of cervical cancer

• See your doctor regularly for a Pap test that can find cervical precancers. Follow up with your doctor, if your Pap test results are not normal.
• Get the HPV vaccine. It protects against the types of HPV that most often cause cervical, vaginal, and vulvar cancers. It is recommended for preteens (both boys and girls) aged 11 to 12 years, but can be given as early as age 9 and until age 26. The vaccine is given in a series of either two or three shots, depending on age. It is important to note that even women who are vaccinated against HPV need to have regular Pap tests to screen for cervical cancer.