OVERVIEW

The cervix is the lower part of the uterus or womb. The cervix of the uterus is known as the neck of the uterus because of its structure and function. It joins the womb to the vagina. Due to this anatomical position of the cervix, it serves as the mediating pathway into the womb and out of the womb to the vagina.

In simple terms, everything that enters the vagina into the womb must pass through the cervix. The internal part of the cervix begins from the internal orifice called the endocervix or the internal cervical canal. The part of the cervix which connects directly to the vaginal cavity is the external orifice also referred to as the ectocervix. The cells that line the surface of the internal cervix are mucous producing glandular columnar epithelial cells.

The cells of the external cervix are flattened and thin squamous epithelial cells. The point of connection between the external cervix and the internal cervix the transformation zone has a mixture of columnar and squamous cells.

Because the cervix mediates between the womb and vagina, it is at risk of infections from the uterus and the vagina alike. Cervical cancer is one of the most common cancers in females. Most of the cervical cancers diagnosed are known to be caused by the Human Papilloma Virus (HPV). Because of increased medical procedures and screenings, the incidence of cervical cancer has been reduced and most women who had precancerous changes in their cervix do not progress to cervical cancer.

DEFINITION

 Cervical cells neoplasm is cervical cancer. Abnormal cell growth of cells of the cervix had the ability to spread to distant organs and/or invade nearby tissues. Most often, the abnormal cell growth begins from the transitional zone, the part where the two predominant epithelial cell types of the cervix confluence. In addition, most cervical cancer incidences are found to originate from the squamous cells.

TYPES OF CERVICAL CANCER 

Cervical cancer is group into different types on the basis of histological findings. In simple terms, the cancerous cells are observed under a microscope and the particular type of cell from which the cancerous cells began determines the type of cancer.

1. SQUAMOUS CELL CARCINOMAS:

Cancer begins from the flat, thin cells lining the external or lower part of the cervix. These cells are the squamous cells. This type of cancer is known to begin from the part where the endocervical cells meet the ectocervical cells called the transformation zone. Squamous cell carcinomas of the cervix are the most common type of cervical cancers diagnosed. It ranks as the most common type with a percentage of about 80% in all cervical cancer cases.

2. ADENOCARCINOMAS:

This refers to cancer of the cervix that originates from the glandular mucous producing cells lining the internal or upper part of the cervix. These cells are the columnar epithelial cells. The name adenocarcinoma is simplified as adeno(glandular) and carcinoma(cancer of epithelial origin). So it means cancers of glandular epithelial cells. It accounts for about 20% of all cervical cancer cases.

3. MIXED CELLS CARCINOMA:

This type of cancer is not common. This cancer originates from both columnar and squamous epithelial cells. It is also called adenosquamous carcinoma of the cervix because the cells of the cancer are both internal and external cervical cells mixed together.

4. Other types:

These are very rare types of cancers. These type of cancers are;

• Cervical lymphomas:

This is a very rare type of cancer that originates from the lymphatic cells of the cervix. Specifically, the cells located in the lymph nodes of the cervix. This type of cancer in clearer terms will be called an Intra nodal or nodal cervical lymphoma.

• Melanoma of the cervix:

This kind of cancers affect the melanin or pigment-producing cells located in the cervix. In this situation, the melanocytes increase uncontrollably and mass up in the cervix. It is a very rare form of cervical cancer. Clinically melanoma of cervix is differentiated from Cervical Melanosis in which the melanocytes produce too much melanin and cause hyperpigmentation of cervical cells but there is no overproduction or increase in the number of melanocytes.

• Sarcoma of the cervix:

This is also a very rare type of cancer which originates from the connective tissues of the cervix. It affects the muscles, blood vessels and other connective tissues of the cervix.

EPIDEMIOLOGY

Cervical cancer is ranked as the fourth cause of cancer deaths in females. Due to the lack of requisite health facilities in developing countries, the screening processes which help to detect precancerous changes in the cervix before it becomes malignant are not common. This is the reason why cervical cancer ranks as the leading cause of cancer deaths in developing countries.

About 80% of all cervical cancer fatalities in the world are recorded in the underdeveloped and developing countries. It is estimated that in India, about 123,000 cervical cancer cases are recorded each year.

A large number of about 68,000 women die out of the cases diagnosed per year. The coverage of screening in developing countries is estimated at around 20%. On the contrary, the screening coverage programs for cervical cancer in developed countries rise by about 65%.

The National Cancer Registry Program after analysis and appropriate surveys on common cancers that affect women stated that cancers in females normally affect two main sites; The breast and the cervix. Cervical cancer is ranked as the second most common cancer of females after breast cancer.

It is estimated that about 53,000 cases of cervical cancer were diagnosed in the year 2012 in the world. About 270,000 women died out of the cases diagnosed. Cervical cancer is ranked as the 8th most common cancer in the United States. Also, cervical cancer ranks as the 12th most frequently diagnosed cancer among women in the United Kingdom.

The five-year survival rate of cervical cancer in developing countries is low because the cancer is mostly diagnosed in its late stages. This makes treatment very difficult and prognosis very poor. Recently, protection during sexual activities like usage of condoms has reduced the incidence rate of cervical cancers by reducing the rate of Human papilloma viral infections.

CANCER RESEARCH BUDGET PER YEAR

Good health is a priority to all humans. To maintain this concept of good health in the world, constant research programs are conducted in order to find new techniques and procedures to prevent and manage cancer cases.

These research procedures are done purposely to reduce the frequency of occurrence of cancer cases and other systemic diseases and also to manage them appropriately when they happen to reduce fatalities. Obviously, these research procedures come at a very huge cost. Because of this, the government generates funds specifically for cancer research programs. To support this, the National Institute of health in the United State allocated about 16000 million dollars from the years 2015 to 2017. This states an average amount of 5300 million dollars is given to the National Cancer Institute for cancer research procedures.

Considering cervical cancer, a special amount of money is raised purposely for it. The amount of money raised for cervical cancer research procedures from the year 2012 to 2017 is about 400 million dollars. Cervical cancer is a major problem in the world and developing countries to be specific. Due to the low rates of screening programs and education which creates awareness of the causes of cervical cancer in developing countries where the incidence and fatalities are high.

This on a large scale is due to poverty. In light of this, not only the government but some health companies and charitable organizations generate funds to help in screenings for early detection. This generated amount of money is also used to support treatment procedures in developing countries.

CAUSES OF CERVICAL CANCER

The cause of cervical cancer just like all other cancers known is due to genetic alterations or mutations. But with cervical cancer, the mutations on the genes chiefly an acquired mutation. The Incidence of cervical cancer cases due to Spontaneous mutations or inherited germ-line mutation is very uncommon. The chief cause or risk factor of cervical cancer is explained below.

Human Papilloma Virus (HPV):

Infection caused by the HPV virus is a sexually transmitted infection. Why is that HPV is the most common risk factor for cervical cancer? This Virus causes genital infections and most women who are infected with HPV totally recover within an estimated period of 2 years. Meaning, not all HPV infections cause cancer. Most often, not all the types of HPV cause cancer but the high-risk types.

These strains can cause persistent infections and they are HPV16 and HPV18. For the human papillomavirus to cause cancer these risk factors make it possible;
1. Having first sexual intercourse at a very early stage in life.
2. Having multiple sexual partners and unprotected sex.
3. Being immunodeficient.

*Note. For HPV to cause precancerous changes in the cervix, there must be a persistent or continual infection. This persistent infection can only occur most commonly when the HPV is not totally eradicated from the body of an infected woman. The most involving risk of the virus is, not being cleared of the woman’s cervix is immunodeficiency patients. In the absence of the risk factors stated above even the high-risk strains cannot cause persistent infections and consequently cannot cause cervical cancers. Lastly, it takes several years or several decades for persistent infections with precancerous changes to cervical cells to develop into cervical cancer.

RISK FACTORS OF CERVICAL CANCER

1. Smoking tobacco products.
2. Low vegetables and fruit diets.
3. Women with immunodeficiency conditions.
4. A woman with multiple sex partners.
5. Continuous unprotected sex.
6. Sexual active from a very early age.
7. Having other co-infections or superinfection like chlamydia.
8. Chronic use of certain birth regulatory drugs.
9. The usage of the estrogen analogue stilbestrol also increases the risk of cervical cancer.
10. A family history of cervical cancer.

PATHOPHYSIOLOGY

Cervical cancer is mostly caused by an acquired genetic mutation. A mutation which is induced primarily by the high-risk human papillomaviruses types 16 and 18. These high-risk viral types make use of two main proteins known as E6 and E7 proteins to cause changes in the cervical lining cells. Because continuous exposure of these proteins is needed to cause changes to the cervical cells, persistent HPV infection is key in causing cervical cancer.

These proteins are oncogenic; meaning they are able to initiate cancer formations. These proteins are able to bind to tumor suppressive genes like p53, and Retinoblastoma genes, and induce changes on them which silence their actions. These mutations in the tumor suppressor genes allow cancer initiating genes or oncogenes to act without any opposition.

This manifest in the cervix with cervical cells which grow rapidly with an abnormal appearance from normal cervical cells. These cells accumulate in the cervix and refuse to die. These cells grow rapidly and are able to spread from the cervix to nearby body parts or distant organs.

CLINICAL MANIFESTATIONS OF CERVICAL CANCER

1. Vaginal bleeding after sex or during sex.
2. Pelvic Pain during or after sex.
3. Irregular menstrual cycle.
4. Abnormal vaginal discharge with an offensive smell.
5. Unexplained loss of weight.
6. Loss of appetite.
7. Paleness due to extensive loss of blood(Anemia).

COMPLICATIONS OF CERVICAL CANCER

These are problems caused due to metastasis or treatment of cervical cancer.
1. Bloody stool due to the invasion of cancer in the rectum.
2. Severe Pain due to spread of cancer unto nerve endings.
3. kidney problems and kidney inflammation in stage 3B cancers causing (hydronephrosis). This is the accumulation of fluid in the kidney due to distention of renal pelvis caused by cervical cancer invasion.
4. Bone marrow depression by cancer drugs leading to infections.
5. Surgical management leads to an inability to conceive a baby due to the removal of the uterus.

PROGNOSIS

The outcome of cervical cancer management just like all other cancers is based on the stage. Women with cancers that can only be detected by the aid of a microscope Stage 1A cancers have an outstanding assurance of survival of about 99%. If cervical cancers are detected early, even women with invasive cancers can have a chance of about 93% survival.

Treatment of women with stage 1 and stage 2 cancers can have a better prognosis compared to that of other stages. The five-year survival rate of Stage 1 cancer is about 90% and that of stage 2 is about 76%.
Obviously, the survival rate for 5 years speedily declines as cancer progresses to the more invasive stage 3 cancer which has a rate of survival around 40%. On the worst account, stage 4 cancers have a very low rate of survival and this is about 14%.
Based on the frequency of occurrence of cervical cancer in the United State and the fatalities recorded in the year 2001, about 4,800 women died of cervical cancer out of the total number of the cases diagnosed. In 2002, the total number of cervical cancer cases numbered around 13000 in the United State.

Due to increasing screening, the cervical cancer incidence rate has reduced drastically by 50% from the 1970s to 2014. Most often the average age range for cervical cancer in women is around 35 getting to 45. But about 16% of women are diagnosed with cervical cancer at a very old age around 65 going. On rare occasions, some women are found to have cervical cancer at very younger ages of 20 and below. The outcome of cervical cancer in developing countries is very poor since most of the cases are detected in the late stages where the cancer is not much responsive to treatment.

ROUTES OF METASTASIS

1. Local spread or local invasion into the vagina and nearby tissues.
2. Hematogenous spread: Cervical cancer cells are found in the lungs and the liver through blood.
3. Lymphatic spread: Cancer Cells are found in Lymph nodes and move to other pelvic organs.

STAGES OF CERVICAL CANCER

Treatment procedures will be just blind attempts when there is no knowledge of the stage of cervical cancer being treated. The stage of cervical cancer is needed for management because it dictates the type of management or treatment approach.

Because the stage affects the management, then it is simple to say the stage also depicts the outcome or prognosis of cervical cancer and all other cancers. Cancer is staged based on these; tumor size, the number of lymph nodes, metastasis or spread of tumor cells. This is the TNM classification for cancer staging.

1. Stage 0(Tis, N0, M0):

The cancer is located only in the part of the cervix it began from. It has not spread through the cells of the cervix. It is called Carcinoma in place (Carcinoma In situ).

2. Stage 1:

• Stage 1A(T1, N0, M0):

Cancer is of small size and occupies an area of about 3mm in the cervix and has invaded deep tissues of the cervix from the cervical lining but not any lymph node. The tumor is less than 2cm in size.

• Stage 1B(T1, N0, M0):

Cancer has invaded deep tissue of cervix and the size area occupied is about 5mm. Cancer has become bigger but has not entered any lymph node. The tumor is about 4cm in size.

3. Stage 2:

• Stage 2A(T2, N0, M0):

Cancer has grown bigger and has extended beyond the cervix into the vagina tissues but it has not invaded lymph nodes or any distant organs.

• Stage 2B(T2, N0, M0):

Cancer has grown into vaginal tissues and grown bigger into the fibrous and fatty connective tissue of the uterus (parametrium). But the cancer cells have not invaded lymph nodes or distant organs.

4. Stage 3:

• Stage 3A(T3, N0, M0):

The tumor has grown bigger into the very lower parts of the vagina. The tumor is in the lower third of the vagina but it has not yet invaded the pelvic wall. There is no lymph node involvement nor distant metastasis.

• Stage 3B(T3, N1, M0):

Cancer has grown bigger and has invaded the pelvic wall. The cancer is in the lower third of the vagina as well. Cancer has invaded regional lymph nodes but no distant lymph nodes are invaded. There is no distant metastasis.

5. Stage 4(T4, N1, M1):

Cancer has grown into all regional and distant lymph nodes. Cancer has entered the main blood vessels and has moved to distant organs like the liver and the lungs.

DIAGNOSIS OF CERVICAL CANCER

1. Screening tests:

These kinds of tests are done mostly for checkup reasons. Women who do these tests do it with no idea if they have cervical cancer risks or precancerous changes in their cervix.

• Papanicolaou test:

This test is done by scraping cervical cells and examining them for abnormalities. This test helps to find precancerous changes in the cervix and help to treat immediately to prevent it from becoming malignant. It is popularly known as the Pap Test.

• HPV-DNA:

This is also a type of test done to find the load of HPV in a woman. High levels of HPV DNA in woman shows high-risk of developing cervical cancer.

2. Diagnostic procedures:

These tests are done mostly when someone goes to see their doctor in the hospital because of cervical cancer suspicions. These can also be done for other disease and cancerous changes of the cervix can be found accidentally.

I. Tissue biopsy:

Cells of the cervix are obtained and analyzed for abnormalities and cancerous changes. A lot of procedures are used and some are;

a) Punch biopsy:

Cervical samples are harvested with a sharp instrument.

b) Endocervical Curettage:

Samples are scraped from the cervix with a spoon-like instrument.

c) Cone biopsy:

This procedure harvest deep tissues of the cervix in the shape of a cone for analysis, mostly under general anaesthesia.

d) Wire loop electrical procedure:

An electrical wire is heated and used to harvest cervical tissues under local anaesthesia.

II. Colposcopy:

There is the use of an instrument called a colposcope to directly observe the abnormalities of cells in the cervix. In this procedure, a sterile speculum is used to keep the cervix opened to allow the use of the colposcope.

III. Imaging techniques:

X-ray, Positron Emission Tomography (PET), CT, and others to observe the lungs, and the liver for possible metastasis of cancer.

PREVENTION OF CERVICAL CANCER

1. Constant screening activities to detect precancerous changes in the cervix for early treatment(pap test, HPV-DNA test).
2. Avoid sexual promiscuity.
3. Eating enough fruits and vegetables.
4. Effective Protection during sexual activities.
5. Avoid chronic use of contraceptives.
6. Avoid smoking tobacco products.
7. Use of HPV vaccines. Eg; Cervarix, Gardasil.

TREATMENT OF CERVICAL CANCER

1. Surgery:

This is normally a curative means for cervical cancers which are detected very early. There is no reoccurrence because uterus and cervix are removed.

A. Simple hysterectomy:

The uterus and cervix are removed.

B. Radical hysterectomy:

The uterus, cervix, and upper part of the vagina, and some pelvic lymph nodes are removed.

C. Radical cervicectomy:

The uterine cervix, the upper part of the vagina, and nearby lymph nodes are removed.

2. Chemotherapy:

Drugs are used to kill cancer cells. Example of Drugs used are; Carboplatin, paclitaxel, gemcitabine, etc….

3. Radiotherapy:

High energy light rays are used to kill cervical cancer cells.

A. Internal radiotherapy:

Cancer Cells are Killed by radiation from inside the body(brachytherapy). A radioactive implant is put in the tissues of the cervix to deliver high energy rays to kill cancer cells.

B. External radiotherapy:

Light rays are directly focused on the cervix to kill cancerous cells.