Immunohistochemical Pathogenesis Squamous Cell Carcinoma Of The Cervix Biology Essay

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The squamous cell carcinoma is the most common type of cervical cancer. Many women are diagnosed with this type in various countries, and many die each year although cases have declined. The main reason for decline is the increased use of the Pap test, which detects pre-cancerous cells or early-stage cancers when they can be treated most effectively. It is important to recognize this cancer because of poor prognosis. The clinical, histological and Immunohistochemical features and recent advances of this disease are summarized and discussed in this essay. The epidemiology and current concept on pathogenesis are examined.

The cervix is the lower part of the uterus (womb) sometimes called the uterine cervix. The body of the uterus (the upper part) is where a baby grows, and the cervix connects here to the vagina (birth canal). This structure dilates during childbirth to allow the baby to traverse the birth canal. The part cervix that is closest to the body of the uterus is called the endocervix. The part next to the vagina is the exocervix (or ectocervix). The two main types of cells covering the cervix are squamous cells (on the exocervix) and glandular cells (on the endocervix). The place where these two cell types meet is called the transformation zone and most cervical cancers start here. Squamous cell cancers arise from the squamous epithelium and the cause is unknown. There is a strong association with certain subtypes of the Human Papilloma Virus (HPV) for the squamous cell cancers. HPV can be transmitted sexually, so there is an association with sexual activity. (Society., 2011)

CLINICAL FEATURES.

There may be no symptoms of a very early cervical cancer, but by the time it is large enough to be detected visually it is usually symptomatic with abnormal bleeding. Often this abnormal bleeding occurs after sexual intercourse. The new blood vessels formed by the cancer are often abnormal and break easily which is why bleeding is a sign of cancer. The cancer also outgrows some of its blood supply, so portions of it are deficient in oxygen. This causes some of the cells to die and for the tissue to become infected. In the cervix this causes a watery or foul discharge that will be noticeable and resistant to most treatments for the usual vaginal infections. As the cancer increases in size it grows laterally toward the pelvic wall. The tubes from the kidneys (ureters) that bring urine to the bladder are obstructed. If that happens to both of the ureters, then this will result in renal failure, coma and death. If the cancer grows into the pelvic wall it will press on the nerves that go to the leg and cause unremitting leg pain. Cervical cancers can spread by way of the lymphatic system, which follows the large blood vessels. If the pelvic lymph nodes on one side of the pelvis become obstructed with cancer then that will cause swelling in the leg on that side. These are signs of advanced cancer. (www.gyncancer.com/cervix)

PATHOLOGIC FEATURES:

(a)Histological features

Most cervical cancers begin in the cells lining the cervix. These cells do not suddenly change into cancer. Instead, the normal cells of the cervix first gradually develop pre-cancerous changes that turn into cancer. Histologically, they are small round-to-oval cancer cell nests with peripheral cell palisading seen budding from the basal cell layer of the uterine cervix showing carcinoma in situ. The histological features include-:, the number of the cancer nests per 22.5mm2 section, stromal reaction, space formation in the cancer nests, foamy cell or foreign body giant cell (FBG) clusters, and epithelial membrane antigen reactivity on the specimens excised after radiation therapy. (Society., 2011)

(b) Immunohistochemical features

Some patients show viable cancer cell predominance on their specimens excised with drill biopsy after radiation therapy. These specimens are stained with routine haematoxylin and eosin staining as well as with antibodies against epithelial membrane antigen (EMA), carcinoembryonic antigen, and S-100 protein. After testing the following is observed, more or less than 20 cancer nests, granulomatous stroma or non, presence or absence of the space formation, absence or presence of the foamy cell or foreign body giant cell clusters, and epithelial membrane antigen negativity or positively favourable for local control of the cervical cancer with radiation therapy. These data may suggest that radiation sensitivity of cancer and stromal reaction for drainage of the degenerated cancer debris is important for local control of the tumours. (Society., 2011)

(c) Diagnosis

The diagnosis of cervical cancer is usually not difficult. It is usually big enough to be seen and can be biopsied. If it arises from up inside the cervical canal then it may not be visible. This will require that a portion of the cervix be removed for diagnosis. These large biopsies can be accomplished by either a loop electrosurgical excision procedure (LEEP) or cone procedure. A major mistake is to rely on a Pap test to rule out a cancer in a woman who has symptoms or findings that could be due to a cancer. A normal Pap test never excludes a cancer. Cancer can only be excluded by the proper biopsies. It is known that about 10% of women with an obvious cancer of the cervix will have a Pap test that is essentially normal, but an abnormal Pap test is not a diagnosis. This is because there is so much inflammation and dead cell debris that it masks the cancer cells. Very rarely, the cervix may be too small or inaccessible to biopsy properly. In these situations a simple hysterectomy may have to be done for diagnosis. An abnormal Pap test is not a diagnosis. (Society., 2011)

(d) Recent advances. New ways to prevent and treat cancer of the cervix are being researched. Some of the promising new developments include the following:

1. HPV vaccines

Vaccines have been developed to prevent infection with some of the HPV types associated with cervical cancer. Currently available vaccines are intended to produce immunity to HPV types 16 and 18, so that women who are exposed to these viruses will not develop infections. Vaccines are also being developed to prevent infection with some of the other HPV types that also cause cancer. Long-term studies are being done to see how well these vaccines will reduce the risk of cervical cancer. Some experimental vaccines are also being studied for women with established HPV infections, to help their immune systems destroy the virus and cure the infection before a cancer develops. Still other vaccines are meant to help women who already have advanced cervical cancer that has recurred or metastasized. These vaccines attempt to produce an immune reaction to the parts of the virus (E6 and E7 proteins) that make the cervical cancer cells grow abnormally. It is hoped that this immunity will kill the cancer cells or stop them from growing. (Society., 2011)

2. Targeted therapy

As researchers have learned more about the gene changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy drugs. They often have different (and less severe) side effects. These drugs may be used alone or with more traditional chemotherapy. Pazopanib is a type of targeted therapy drug that blocks the effect of certain growth factors on cancer cells. In studies of patients with advanced cervical cancer, it helped them live longer. Other targeted therapy drugs that have been studied in cervical cancer include bevacizumab (Avastin®) and lapatinib (Tykerb®). (Society., 2011)

3. Hyperthermia

Some research indicates that adding hyperthermia to radiation may help keep the cancer from coming back and help patients live longer. Hyperthermia is a treatment that raises the temperature in the area where the tumour is, most often by using radiofrequency antennae placed around the patient.

4. Drug treatment of pre-cancers

Standard treatment of cervical pre-cancer such as cervical intraepithelial neoplasia (CIN) includes cryotherapy, laser treatment, and conisation. In one study, patients with CIN2 or CIN3 took a drug called diindolylmethane (DIM) for 12 weeks. Follow-up testing showed improvement - in some women, the CIN went away completely. Many clinical trials are testing new chemotherapy drugs, new ways of giving radiation therapy, and new combinations of surgery and radiation therapy or chemotherapy. (Society., 2011)

EPIDEMIOLOGY.

Incidence of squamous-cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence are usually around 66 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females.

PATHOGENESIS 

1. Smoking

Women who smoke are about twice as likely as non-smokers to get cervical cancer. Smoking exposes the body to many cancer-causing chemicals that affect organs other than the lungs. These harmful substances damage the DNA of cervix cells and may contribute to the development of this disease. It also makes the immune system less effective in fighting HPV infections.

2. Immunosuppression

Human immunodeficiency virus (HIV), the virus that causes AIDS, damages the body's immune system and places women at higher risk for HPV infections. Scientists believe that the immune system is important in destroying cancer cells and slowing their growth and spread. In women with HIV, a cervical pre-cancer might develop into an invasive cancer faster than it normally would. Another group of women at risk of cervical cancer are women receiving drugs to suppress their immune response, such as those being treated for an autoimmune disease or those who have had an organ transplant.

3. Chlamydia infection

Chlamydia is a relatively common kind of bacteria that can infect the reproductive system. It is spread by sexual contact. Chlamydia infection can cause pelvic inflammation, leading to infertility. There is a high risk of cervical cancer in women who had Chlamydia infection in the past or current. Infection with Chlamydia often causes no symptoms in women.

4. Diet

Women with diets low in fruits and vegetables may be at increased risk for cervical cancer. Also overweight women are more likely to develop adenocarcinoma of the cervix.

5. Oral contraceptives (birth control pills)

There is evidence that taking oral contraceptives (OCs) for a long time increases the risk of cancer of the cervix. Research suggests that the risk of cervical cancer goes up the longer a woman takes OCs, but the risk goes back down again after the OCs are stopped. A woman with multiple sexual partners should use condoms to lower her risk of sexually transmitted illnesses no matter what other form of contraception she uses.

6. Multiple full-term pregnancies

Women who have had 3 or more full-term pregnancies have an increased risk of developing cervical cancer. No one really knows why this is true. One theory is that these women had to have had unprotected intercourse to get pregnant, so they may have had more exposure to HPV. Also, studies have pointed to hormonal changes during pregnancy as possibly making women more susceptible to HPV infection or cancer growth. Another thought is that the immune system of pregnant women might be weaker, allowing for HPV infection and cancer growth.

7. Poverty

Poverty is also a risk factor for cervical cancer. Many women with low incomes do not have ready access to adequate health care services, including Pap tests. This means they may not get screened or treated for cervical pre-cancers.

8. Family history of cervical cancer

Cervical cancer may run in some families. If your mother or sister had cervical cancer, your chances of developing the disease are 2 to 3 times higher than if no one in the family had it. Some researchers suspect that some instances of this familial tendency are caused by an inherited condition that makes some women less able to fight off HPV infection than others. (Society., 2011)

CONCLUSION.

Squamous cell carcinoma of the cervix is a rare type of cancer and is usually caused by poor prognosis. Most early cases of cancers are cured; but the advanced cancers are not. If it is removed surgically chances of recurring are minimal. If it recurs it means that the cancer cell already spread by the time the cancer was removed. I can take a couple of years to grow large enough to be detected; about 85% will recur within the first two years after treatment. If there has been no recurrence by five years, then the cancer is unlikely to recur and is considered cured. This cancer occurs during child bearing years, between 20 years and 40 years obviously in females and can be found anywhere. Abnormal cells can be destroyed in many ways such as through surgery, a technique called "needle and ball diathermy [1] , and chemotherapy which is delivering drugs throughout the body, to slow the cancer's progression, and reduces pain. All sexually active women are at risk for the development of cervical cancer. The risk seems to be increased with smoking and promiscuity of the woman or her male partner. This is one cancer that can be prevented, in most cases, by screening for the premalignant changes.

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