CERVICAL CANCER

Cervical cancer is a malignant neoplasm arising from cells originating in the cervix uteri. One of the most common symptoms of cervical cancer is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer has progressed to an advanced stage. Treatment usually consists of surgery (including local excision) in early stages, and chemotherapy and/or radiotherapy in more advanced stages of the disease. Cancer screening using the Pap smear can identify precancerous and potentially precancerous changes in cervical cells and tissue. Treatment of high-grade changes can prevent the development of cancer in many victims. In developed countries, the widespread use of cervical screening programs has dramatically reduced the incidence of invasive cervical cancer. Human papillomavirus (HPV) infection appears to be a necessary factor in the development of almost all cases (90+%) of cervical cancer. HPV vaccines effective against the two strains of this large family of viruses that currently cause approximately 70% of cases of cervical cancer have been licensed in the U.S, Canada, Australia, and the EU. Since the vaccines only cover some of the cancer-causing ("high-risk") types of HPV, women should seek regular Pap smear screening, even after vaccination. The cervix is the narrow portion of the uterus where it joins with the top of the vagina. Most cervical cancers are squamous cell carcinomas, arising in the squamous (flattened) epithelial cells that line the cervix. Adenocarcinoma, arising in glandular epithelial cells is the second most common type. Very rarely, cancer can arise in other types of cells in the cervix. Signs and Symptoms The early stages of cervical cancer may be completely asymptomatic. Vaginal bleeding, contact bleeding, or (rarely) a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs or elsewhere. Symptoms of advanced cervical cancer may include: loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy bleeding from the vagina, bone fractures, and/or (rarely) leakage of urine or faeces from the vagina (rarely).

Causes
Infection with some types of human papilloma virus (HPV) is the greatest risk factor for cervical cancer, followed by smoking. Other risk factors includehuman immunodeficiency virus. Not all of the causes of cervical cancer are known, however, and several other contributing factors have been implicated. Human papillomavirus Human papillomavirus is the cause of 70% of cervical cancer globally. Women who have many sexual partners (or who have sex with men who have had many other partners) have a greater risk. Of the 150-200 types of HPV known, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66), and 12 as lowrisk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).Types 16 and 18 are generally

acknowledged to cause about 70% of cervical cancer cases. Together with type 31, they are the prime risk factors for cervical cancer. Genital warts, which are a form of benign tumor of epithelial cells, are also caused by various strains of HPV. However, these serotypes are usually not related to cervical cancer. It is common to have multiple strains at the same time, including those that can cause cervical cancer along with those that cause warts. The medically accepted paradigm, officially endorsed by the American Cancer Society and other organizations, is that a patient must have been infected with HPV to develop cervical cancer, and is hence viewed as a sexually transmitted disease (although many dispute that, technically, it is the causative agent, not the cancer, that is a sexually transmitted disease), but most women infected with high risk HPV will not develop cervical cancer. Use ofcondoms reduces, but does not always prevent transmission. Likewise, HPV can be transmitted by skin-to-skin-contact with infected areas. In males, there is no commercially available test for HPV, although HPV is thought to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative.

Diagnosis
Biopsy While the pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix. Medical devices used for biopsy of the cervix include punch forceps or SpiraBrush CX. Colposcopic impression, the estimate of disease severity based on the visual inspection, forms part of the diagnosis. Further diagnostic and treatment procedures are loop electrical excision procedure (LEEP) and conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.

Precancerous lesions Cervical intraepithelial neoplasia, the potential precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used. The naming and histologic classification of cervical carcinoma percursor lesions has changed many times over the 20th century. The World Health Organization classification[18][19] system was descriptive of the lesions, naming them mild, moderate or severe dysplasia or carcinoma in situ (CIS). The term, Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatment.It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3. More recently, CIN2 and CIN3 have been combined into CIN2/3. These results are what a pathologist might report from a biopsy. These should not be confused with the Bethesda System terms for Pap smear (cytopathology) results. Among the Bethesda results: Low-grade Squamous Intraepithelial Lesion

(LSIL) and High-grade Squamous Intraepithelial Lesion (HSIL). An LSIL Pap may correspond to CIN1, and HSIL may correspond to CIN2 and CIN3, however they are results of different tests, and the Pap smear results need not match the histologic findings. Cancer subtypes Histologic subtypes of invasive cervical carcinoma include the following: Though squamous cell carcinoma is the cervical cancer with the most incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades.

squamous cell carcinoma (about 80-85% adenocarcinoma (about 15% of cervical cancers in the UK adenosquamous carcinoma small cell carcinoma neuroendocrine tumour glassy cell carcinoma villoglandular adenocarcinoma

Non-carcinoma malignancies which can rarely occur in the cervix include

melanoma lymphoma

Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers. For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the original clinical stage. Staging Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervicalconization.

Prevention
Screening The widespread introduction of cervical screening by the Papanicolaou test, or Pap smear for cervical cancer has been credited with dramatically reducing the incidence and mortality of cervical cancer in developed countries. Pap smear screening every 35 years with appropriate follow-up can reduce cervical cancer incidence by up to 80%. Abnormal results may suggest the presence of pre cancerous changes allowing examination and possible preventive treatment. If precancerous disease or cervical cancer is detected early, it can be monitored or treated relatively noninvasively, with little impairment of fertility. Cervical cancer screening is typically recommended starting at age 21. Recommendations for how often a Pap smear should be done vary from once a year to once every five years, in the

absence of abnormal results. Guidelines vary on how long to continue screening, but well screened women who have not had abnormal smears can stop screening about age 60 to 70. Liquid-based cytology is another potential screening method. Although it was probably intended to improve on the accuracy of the Pap test, its main advantage has been to reduce the number of inadequate smears from around 9% to around 1%. This reduces the need to recall women for a further smear. The United States Preventive Services Task Force supports screening every 5 years in those who are between 30 and 65 years when cytology is used in combination with HPV testing. Vaccination There are two HPV vaccines (Gardasil and Cervarix) which reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93%. HPV vaccines are typically given to women age 9 to 26 as the vaccine is only effective if given before infection occurs. The vaccines have been shown to be effective for at least 4 to 6 years, and it is believed they will be effective for longer; however, the duration of effectiveness and whether a booster will be needed is unknown. The high cost of this vaccine has been a cause for concern. Several countries have considered (or are considering) programs to fund HPV vaccination. Condoms Condoms are thought to offer some protection against cervical cancer. Evidence on whether condoms protect against HPV infection is mixed, but they may protect against genital warts and the precursors to cervical cancer. They also provide protection against other STDs, such as HIV and Chlamydia, which are associated with greater risks of developing cervical cancer. Condoms may also be useful in treating potentially precancerous changes in the cervix. Exposure to semen appears to increase the risk of precancerous changes (CIN 3), and use of condoms helps to cause these changes to regress and helps clear HPV. One study suggests that prostaglandin in semen may fuel the growth of cervical and uterine tumours and that affected women may benefit from the use of condoms. Nutrition Vitamin A is associated with a lower risk as is vitamin B12, vitamin C, vitamin E, and betacarotene.

Treatment
The treatment of cervical cancer varies worldwide, largely due to large variances in disease burden in developed and developing nations, access to surgeons skilled in radical pelvic surgery, and the emergence of "fertility sparing therapy" in developed nations. Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed as well. Alternatives include local surgical procedures such as a loop electrical excision procedure (LEEP) or cone biopsy. For 1A1 disease, a cone biopsy (aka cervical conization) is considered curative. If a cone biopsy does not produce clear margins, one more possible treatment option for patients who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the patient is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the patient has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation. A radical trachelectomy can be performed abdominallyor vaginallyand there are conflicting opinions as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two to three day hospital stay, and most women recover very quickly (approximately six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage. It is generally recommended to wait at least one year before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, it is recommended for patients to practice vigilant prevention and follow up care including pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 34 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive. Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Patients treated with surgery who have high risk features found on pathologic examination are given radiation therapy with or without chemotherapy in order to reduce the risk of relapse. Larger early stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy.

Advanced stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin for women with late-stage (IVB) cervical cancer treatment. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline.

Nursing Considerations
Listen to the patients fears and concerns, and offer reassurance when appropriate. Encourage the patient to use relaxation techniques to promote comfort during the diagnostic procedures. Monitor the patients response to therapy through frequent Pap tests and cone biopsies as ordered. Watch for complications related to therapy by listening to and observing the patient. Monitor laboratory studies and obtain frequent vital signs. Understand the treatment regimen and verbalize the need for adequate fluid and nutritional intake to promote tissue healing. Explain any surgical or therapeutic procedure to the patient, including what to expect both before and after the procedure. Review the possible complications of the type therapy ordered. Remind the patient to watch for and report uncomfortable adverse reactions. Reassure the patient that this disease and its treatment shouldnt radically alter her lifestyle or prohibit sexual intimacy. Explain the importance of complying with follow up visits to the gynecologist and oncologist.