Cervical cancer begins with the abnormal growth of cells lining the cervix. The cervix is located in the lower, more superficial, region of the uterus. The two types of cells that make up the cervix include nonkeratinizing, stratified squamous cells on the exocervix and mucus-secreting, columnar cells on the endocervix. The transformation zone contains the squamocolumnar junction where the columnar and the squamous cells meet. This area is the embryonic cell population that is involved in cervical remodeling and is the site of initial growth for most cervical cancers.
The carcinoma usually either develops from an adenocarcinoma from the glandular columnar cells (about 10% of all cervical cancers) or squamous cell carcinoma from the squamous cells of the exocervix (about 85%). It is also possible to have a mix of these two carcinomas in adenosquamous carcinomas. In squamous cell carcinomas, the abnormal growth may be polypous or infiltrative. The cells are affected by a decrease in glandular activity, cell necrosis and keratinization. However, if the tumor is 3mm or less, there is a low risk of metastasis, spreading to other areas of the body, or reoccurrence.
The subtypes of adenocarcinomas include mucinous, intestinal, endometrioid, clear cell, serous papillary and adenosquamous. Ninety percent of the growth of the tumors is HPV-related; although not everyone who has Human Papillomavirus develops cervical cancer. The viral infection appears to alter expression of genes associated with cellular proliferation, while also suppressing the immune system. The second stage of pre-cancerous cell growth is defined by the growth of new blood vessels to the cancerous cells.
Communication amongst different cell types facilitates the growth of the new blood vessels as seen in changes occurring in both the epithelial and stromal cells. The characteristics of the third stage of precancerous growth in squamous cell carcinoma cervical tissue show alterations in the role of adhesion proteins and enzymes that usually remodel the extracellular matrix of the cell. This could be due to viral influence or just overcrowding of cells. Furthermore, pro-invasive genes are activated to spread cancerous growth to the basement membrane.
Development of symptoms increases as the tumor grows larger. The growing tumor, now with access to a blood supply, can become ulcerated, or split. This is the main cause of vaginal bleeding. Bleeding is also common after vaginal intercourse, after menopause, between periods and having periods heavier than normal. As the tumor reaches the lymph nodes in the region, pain, lower extremity edema and deep venous thrombosis develop. Opportunistic anaerobic infection of the necrotic tissue creates a foul-smelling vaginal discharge.
Renal failure is a potential symptom due to compression of the ureter due to the tumor growth and infection of nearby cells causing the kidneys to enlarge and malfunction. Other symptoms include loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, bone fractures, swollen legs and rarely, leakage of urine or feces from the vagina. Back pain develops from invasion of the sciatic nerves roots by the metastatic cancer. From the para-aortic nodes, the cancerous cells extend to the vertebrae and nerve roots, causing back pain and swelling of the lower limbs.
Seeing a gynecologist once symptoms present, is an extremely important first step in treatment. However, having regular pap smears and physical exams can prevent the tumor from growing large enough to elicit symptoms. A pap test, HPV test, physical exam and medical history are the first line screenings. An abnormal pap test will indicate a need for further diagnostic testing. Lymph nodes can be checked for metastasis of the tumor. A colposcopy and endocervical scraping can be performed to check for cancer cells around the cervix.
Once a biopsy is completed, identification of the stage of the cancer is pertinent to the type of treatment required. Stage depends on the size of the tumor, depth of invasion and how far it has spread past the original site. In early stages, surgery or radiation is combined with chemotherapy. More advanced stages call for radiation combined with chemotherapy. Chemotherapy alone is not enough to destroy the cancerous cells. Cure may not always be an option, in which case palliative treatment, or treatment for the purpose of relieving symptoms, is more useful for a longer and better quality life.
There are many different forms of surgery available depending on which stage the cancer has progressed to. Cryosurgery involves using liquid nitrogen to freeze a metal probe and placing it directly on the affected area, the cervix. Another option is laser surgery, in which a focused laser beam is directed toward the cervix in order to burn off the cancerous cells or to take a biopsy for further research of the specific stage. These two procedures are performed under a local anesthesia and can only be used on stage 0, or noninvasive cancer, the earliest stage.
Conization is when a cone-shaped piece of tissue from the cervix is removed with a surgical knife, laser knife, or with a thin wire heated by electricity. This procedure is primarily used as a diagnostic test, since a treatment measure would require multiple sessions to make sure everything has been removed. A hysterectomy is another option for early stage cervical cancer, in which the uterus and cervix are removed. Women with later stage 1 are usually treated with a trachelectomy, where the cervix and the upper part of the vagina are removed, but not the uterus.
Recurrent cervical cancer requires a more extensive operation in which the uterus, vagina and cervix are removed potentially along with the bladder, vagina, rectum and part of colon, depending on how far the cancer has spread. Radiation can be performed in two methods: external beam radiation or brachytherapy. Radiation given from the outside of the body would characterize external beam radiation (EBRT). It is given 5 days a week for 6-7 weeks. Side effects of EBRT include fatigue, upset stomach, diarrhea, nausea/vomiting and skin changes, ranging from temporary redness to peeling.
Irritation in the bladder, soreness and sensitivity in the vulva and vagina, menstrual changes, and low blood cell counts are all symptoms of EBRT. Brachytherapy is internal radiation therapy in which a source of radiation is placed inside the vagina, near the cancer. This form of radiation is usually used in addition to EBRT. Low dosage can be completed in a few days if inpatient or in a few weeks if a high dose rate is used as an outpatient procedure. This form of therapy has many of the same side effects of EBRT with an addition of vaginal dryness and scar tissue in the vagina, making intercourse painful.
Radiation can also weaken the pelvic bones, potentially leading to fractures. Lymphedema is also a potential side effect in which the lymph nodes in the leg drain fluid, leading to severe swelling. When radiation is being used as the main form of treatment, often chemotherapy is paired with it, called concurrent chemoradiation. A low dose of Cisplatin (most common type but there are many others that can be used) is given in cycles with the first one given weekly during radiation via intravenous injection about 4 hours before the radiation procedure.
Cisplatin combined with 5-fluorouracil is the second cycle, given every 4 weeks during radiation. These drugs work systemically so that cancer cells found in all parts of the body are targeted. Side effects of chemotherapy include nausea/vomiting, loss of appetite, hair loss, mouth sores, fatigue and low blood cell counts, which puts the patient at an increased risk for infection (fewer white blood cells), bleeding/bruising (fewer platelets) and shortness of breath (fewer red blood cells). Changes in menstruation, infertility and early menopause are also possible.