cervical cancer

Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic (Canavan &

The possibility to identify premalignant changes on a cervical smear has made screening the major cause for referral of women with possible cervical neoplasia. If cervical cancer is detected early, it can be treated without impairing fertility.

Diagnosis

Diagnosis is made by doing a biopsy of the cervix, which often involves colposcopy, or a magnified visual inspection of the cervix aided by using an acetic acid (e.g. Many researchers recommend that since more than 99% of invasive cervical cancers worldwide contain human papillomavirus, HPV testing should be carried out together with routine cervical screening (Walboomers et al, 1999).

Histology

Types of malignant cervical tumors include the following:

Staging

Cervical cancer is staged by the FIGO staging system, which is based on clinical examination, rather than surgical findings.

The TNM staging system for cervical cancer is analogous to the FIGO stage. no visible lesions IA1 - stromal invasion less than 3 mm in depth and 7 mm or less in horizontal spread IA2 - stromal invasion between 3 and 5 mm with horizontal spread of 7 mm or less IB - visible lesion or a microscopic lesion with more than 5 mm of depth or horizontal spread of more than 7 mm IB1 - visible lesion 4 cm or less in greatest dimension IB2 - visible lesion more than 4 cm Stage II - invades beyond uterus IIA - without parametrial invasion IIB - with parametrial invasion Stage III - extends to pelvic wall or lower ⅓ of the vagina IIIA - involves lower ⅓ of vagina IIIB - extends to pelvic wall and/or causes hydronephrosis or non-functioning kidney IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis IVB - distant metastasis

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.

For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used.

Pathophysiology

The American Cancer Society provides the following list of risk factors for cervical cancer: human papillomavirus infection, smoking, HIV infection, chlamydia infection, dietary factors, oral contraceptives, multiple pregnancies, use of the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer.

The presence of strains 16, 18 and 31 of human papillomavirus (HPV) is the prime risk factor for cervical cancer, and Walboomers et al. (1999) reported that the presence of HPV is a necessary condition for the development of cervical cancer. A virus cancer link with HPV has been found to trigger alterations in the cells of the cervix, leading to the development of cervical intraepithelial neoplasia and cancer.

HPV subtypes 16 and 18 introduce two genes called E6 and E7 which code for proteins that inhibit p53 and Rb, which are two important tumor suppressor genes in humans.

Genital warts are caused by different HPV types, and are not related to cervical cancer.

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. Not all women infected with HPV also develop cervical cancer (Snijders et al, 2006).

Treatment

Microinvasive cancer (stage IA) is usually treated by hysterectomy (removal of the whole uterus including part of the vagina).

If a cone biopsy was not able to produce clear margins, there is one possible option left for those with early stage cervical cancer who would like to preserve their fertility while treating their cervical cancer: a trachelectomy. For those in stage I cervical cancer, which has not spread, this is a viable treatment option. It allows for the preservation of the ovaries and uterus while surgically removing the cervical cancer. Even the most experienced surgeon won't be able to promise that this can be performed beforehand, as the extent of the spread of cervical cancer is unknown until surgical microscopic examination is completed. Due to the fact of 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 womb.

Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy.

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 Food and Drug Administration has approved uses combination of two chemotherapy drugs, Hycamtin and cisplatin for women with late-stage (IVB) cervical cancer treatment.

Epidemiology

Worldwide, cervical cancer is the second most common cancer in women (after breast cancer) and is the third leading killer (behind breast and lung cancer).

In the United States, however, cervical cancer is only the 8th most common cancer of women. About 12,800 women in the United States are diagnosed with cervical cancer and about 4,800 die each year (Canavan & Among gynecological cancers it ranks behind endometrial cancer and ovarian cancer.

In Great Britain, the incidence of cervical cancer has reached alarming proportions in that the mortality in England and Wales in women younger than 35 years rose three-fold from 1967 to 1987. In a study published in 2004 (Peto J et al) scientists from the London School of Hygiene and Tropical Medicine found that had it not been for effective cervical screening, one in 65 of all British women born since 1950 would have died from cancer of the cervix.

A study published in 2002 (Castellsagué et al) reports that male circumcision can reduce the risk of penile human papillomavirus (HPV) infection in the man, and as a result that of cervical cancer in his female partner. The authors do state that "it would not make sense to promote circumcision as a way to control cervical cancer in the United States, where Pap smears usually detect it at a treatable stage". In contrast to this claim, Menczer (2004) quotes research that male circumcision probably does not contribute to a lower incidence of cervical cancer in Jewish populations.

One study suggests that prostaglandin in semen may fuel the growth of cervical and uterine tumours and that affected women might benefit from the use of condoms.

History

Epidemiologists working in the early 20th century noted that:

This led to the deduction that cervical cancer could be caused by a sexually transmitted agent.

Glaxosmithkline has developed a vaccine called Cervarix™ which has been shown to be 100% effective in preventing HPV strains 16 and 18 and is 100% effective for more than four years. The two HPV strains (16 and 18) together cause about 70% of cervical cancer cases.