Cervical Carcinoma

Cervical Carcinoma

Cervix is the lower part of the uterus, which opens into the vagina. The epithelial tissue forms the outer layer of cervix. It is formed of two kinds of epithelial cells: squamous and columnar or glandular. The region of the cervix close to the uterus is called endocervix and the region close to the vagina is called exocervix. Squamous epithelial cells cover the exocervix while the mucous secreting columnar cells are present on the endocervix.

Cancer in the cervix is the third most frequently occurring gynecologic cancer. Cancers develop in the epithelial cells of the cervix. Therefore, they are called carcinomas. The epithelial cells go through a phase called the pre-cancerous stage before they become cancerous. Pre-cancers may or may not change into cancers. The pre-cancerous changes are called cervical intraepithelial neoplasia (CIN), squamous intraepithelial lesion (SIL), and dysplasia.

Types of cervical carcinoma

Since there are two types of epithelial cells, carcinoma of the cervix includes two types: squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma is the predominant type and is detected in 80-90 % cases of cervical cancer. Adenocarcinoma is rarer (approximately 15 %) in comparison to the squamous cell carcinoma, but its frequency may be gradually increasing.

Epidemiology

In Western countries including the United States, screening programs and treatment of precancerous lesions has led to a decline in the rates of cervical cancer.

Causes or Risk factors

Human papilloma virus (HPV) infection: Most cervical cancer is thought to be caused by HPV infection. There are more than a hundred strains of HPV which can infect the genitals, mouth and anus. HPV causes papillomas (or warts) at the site of infection. In most people, the immune system fights this off. In some women, infection with types 16 and 18 can lead to cervical cancer. Vaccination against these strains can prevent many cervical cancers. So can abstinence, use of condoms, limiting the number of sexual partners and avoiding contacting sexually transmitted diseases.

There are now vaccines available and recommended for both teenage girls (Gardasil® and Cervarix®) and boys (Gardasil®) that can prevent most cases of HPV that lead to cervical cancer. It is highly recommended that these vaccines be given before a girl becomes sexually active There is nothing more effective than these vaccines in preventing cervical cancer. By the time girls are into their twenties they have usually been exposed if they are sexually active. The vaccine is not indicated in older women.

Smoking: Smoking is linked to cervical cancer to some extent. Smoking damages the epithelial cells of the cervix, which may eventually cause cervical cancer. Smoking also weakens the immune system.

Immunosuppression: Women whose immune system has been weakened either due to the use immunosuppressive drugs or due to AIDS (caused by HIV infection) are more prone to developing cervical cancer.

Number of pregnancies and sexual partners: More than three full- term pregnancies have been linked to cervical cancer, for reasons not yet clear. Onset of sex at an early age and having too many sexual partners are other risk factors related to cervical cancer almost certainly due to the increased risk of HPV.

Exposure to Diethylstilbestrol (DES): DES is a hormonal drug, which was prescribed to women who had a chance of miscarriage. The drug was used between1940-71. Daughters who were born to such mothers who were given DES have an increased risk of developing cervical cancer. But, the incidence of cervical cancer due to DES exposure is only 0.1%.

Family history of cervical cancer: There may be some genetic basis of cervical cancer. It has been found that the disease is more frequent in women who have a mother or sister affected by the same disease. The immune system is regulated by many genes, which are inherited. Women with a weak immune system are more prone to HPV infection.

Symptoms:

Abnormal vaginal bleeding: Bleeding after intercourse, between periods, or after menopause can be an indication of cervical cancer.

Unusually heavy vaginal discharge: An increased vaginal discharge containing mucous and having a foul smell may be indicative of cervical cancer.

Unusually longer periods: Women with cervical cancer may have longer periods.

Pelvic pain: Pain, which is not due to menstrual cycle, is a symptom of cervical cancer. The pain can be mild or severe.

Other symptoms: Some of the other symptoms that start appearing with the progression of disease are weakness, fatigue, pain in the legs, pain during urination, loss of appetite, leaking of urine and loss of weight.

Diagnosis

Precancerous changes of the cervix and cervical cancer cannot be seen with the naked eye. Special tests and tools are needed to spot such conditions.

Pelvic exam: A doctor can examine a patient’s pelvic organs physically in this procedure. The doctor inserts his gloved finger through the vagina and positions the other hand over the abdomen to feel the organs. This is done along with a pap smear.

Pap smear: Cells scraped from cervix and vagina is viewed under a microscope in the laboratory to detect signs of cancer. This test is called a Pap test. This is initially done by the doctor to recommend the next diagnostic tests that should be performed.

Human papillomavirus (HPV) test: The HPV test or HPV DNA test is a procedure to determine whether the cervical cells are infected by HPV. Molecular diagnostic kits, which have been approved by the United States Food and Drug Administration (US FDA) are: Hybrid Capture Tube test and Hybrid Capture II test (HC II). The tests rely on detection of HPV DNA by a technique called Polymerase Chain Reaction (PCR).

Endocervical curettage (ECC): This is a procedure to test the opening of the cervix.

Colposcopy: A procedure in which a colposcope is used to examine the vagina and cervix. The colposcope gives a magnified view of the area, which is examined. Tissue can be collected from the affected part with the help of an instrument called curette and observed under a microscope for signs of cancer.

Biopsy: The biopsy is done only after a positive Pap test. Cells or small piece of tissue collected from the cervix is viewed under a microscope to detect their characteristics. A different type of biopsy is sometimes done called a cervical cone biopsy, in which a large cone- shaped tissue is removed from the affected area and examined by a pathologist.

Imaging studies with CT scan and MRI: The images provided by CT scan and MRI scan can be useful in staging of cervical cancer.

Treatment

Surgery: There are various kinds of surgery that can be performed by the doctor on the basis of the type of cancer and its stage.

Conization: A cone shaped tissue from the cervix can be excised so that a pathologist can study it. This may remove the entire cancer.

Loop electrosurgical excision procedure (LEEP): This surgical procedure is performed with the help of a thin wire loop through which electrical current is passed. It cuts off the tumor.

Laser surgery: This surgical procedure is performed with the help of a laser beam, which cuts off the tumor precisely.

Cryosurgery: This treatment is mainly used for localized carcinoma. The affected tissue is frozen by an instrument to kill cancer cells.

Total hysterectomy: The surgical removal of uterus and cervix is called total hysterectomy.

Radical hysterectomy: It refers to the excision of uterus together with the parametrium (connective tissue between supracervical portion of the uterus and broad ligaments), part of the vagina and cervix. Other parts of the reproductive system may also be excised.

Modified radical hysterectomy: The surgical removal of uterus, cervix, upper part of the vagina, and ligaments and surrounding tissues. Lymph nodes to which cancer has spread are excised. But, in this surgery, not as much is removed as in the radical hysterectomy.

Pelvic exenteration: This is normally performed at advanced stage of the disease. In this surgery all organs of the pelvic cavity including cervix, vagina and ovaries, are removed. The nearby lymph nodes are also removed. Excretory products are removed from the body through artificial openings. These are collected in a plastic bag. The vagina is re-created with the help of plastic surgery.

Radiation therapy

Radiation therapy is an effective method of treating cervical cancer. It is often used in combination with chemotherapy for better results. X-rays are used to kill the cancer cells in the larynx. This can be done in two ways:

External radiation therapy: Radiation is given by a machine from outside the body at the affected region.

Brachytherapy or Internal radiation therapy: Radioisotopes sealed in a device is placed inside the vagina near the cervix. Radiation emitted from this radioactive substance kills the cancer cells.

Brachytherapy alone may be enough to cure the cancer at an early stage. But, if the cancer has spread, then external radiation therapy together with brachytherapy can be used to reduce the chances of recurrence of cervical cancer.

Chemotherapy

Chemotherapy is the use of drugs to treat cancer. In most patients the drugs are administered through veins. Chemotherapy is given to patients in combination with radiation therapy to enhance the effectiveness of the treatment. Such drugs used with the radiation therapy are called “radiation sensitizers”.

Prognosis

Numerous factors influence the prognosis of cervical cancer. The stage of diagnosis of cervical cancer is one of the very important factors. Cervical cancer diagnosed at stage I and stage II is very much curable. If detected at Stage I and Stage II, cervical cancer patients show a 5 year survival rate of 80-90 % and 50-65 % respectively. The survival rate severely decreases with advancement of the disease. Stage III and Stage IV cervical cancer patients show a 5 year survival rate of 25-35 % and less than 15 % respectively.

Because vaccination against HPV can actually eliminate most cases of cervical cancer, vaccination should be a high priority, as should screening for HPV and precancerous lesions so that early treatment can be undertaken when needed.

References

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  3. Petignat P, Roy M. (2007) Diagnosis and management of cervical cancer. BMJ.;335(7623):765-8.
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  7. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.