Cervical cancer

Cervical cancer is a malignant cancer of the cervix. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages, which has made cervical cancer the focus of intense screening efforts using the Pap smear. In developed countries, the widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer, by 50% or more. Most scientific studies have found that human papillomavirus (HPV) infection is responsible for virtually all cases of cervical cancer Treatment consists of surgery (including local excision) in early stages and chemotherapy and radiotherapy in advanced stages of the disease. An effective HPV vaccine against the two most common cancer-causing strains of HPV has recently been licensed in the U.S. These two HPV strains together are responsible for approximately 70% of all cervical cancers. Experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.

Classification 

Cervical cancer is a carcinoma, typically composed of squamous cells, and is similar in some respects to squamous cell cancers of the head and neck and anus. All three of these diseases may be associated with human papillomavirus infection.

Signs and symptoms

 The early stages of cervical cancer may be completely asymptomatic (Canavan & Doshi, 2000). 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, single swollen leg, heavy bleeding from the vagina, leaking of urine or feces from the vagina, and bone fractures. 

Causes

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

 Human papillomavirus infection

 The most important risk factor in the development of cervical cancer is infection with a high-risk strain of human papillomavirus. Even though HPV is an important risk factor for cervical cancer, most women with this infection do not get cervical cancer and doctors believe other risk factors must come into play for this cancer to develop. Having unprotected sex, especially at a young age, makes HPV infection more likely. Women who have many sexual partners (or who have sex with men who have had many partners) have a greater chance of getting HPV.

Diagnosis

 Biopsy procedures

 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 an acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix.

 Further diagnostic procedures are loop electrical excision procedure (LEEP) and conisation, 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.

 Pathologic types

 Cervical intraepithelial neoplasia, the precursor to cervical cancer, is often diagnosed on examiniation of cervical biopsies by a pathologist. Histologic subtypes of invasive cervical carcinoma include the following: 

    * squamous cell carcinoma (about 80-85%)

    * adenocarcinoma

    * adenosquamous carcinoma

    * small cell carcinoma

    * neuroendocrine carcinoma

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

     * melanoma

    * lymphoma

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 cervical conization.

 The TNM staging system for cervical cancer is analogous to the FIGO stage.

     * Stage 0 - full-thickness involvement of the epithelium without invasion into the stroma (carcinoma in situ)

    * Stage I - limited to the uterus

          o IA - diagnosed only by microscopy; 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

          o 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

          o IIA - without parametrial invasion

          o IIB - with parametrial invasion

    * Stage III - extends to pelvic wall or lower ⅓ of the vagina

          o IIIA - involves lower ⅓ of vagina

          o 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.

Treatment

 Microinvasive cancer (stage IA) is usually treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed as well. An alternative for patients who desire to remain fertile is a local surgical procedure such as a loop electrical excision procedure (LEEP) or cone biopsy.

 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 womb for pathologic evaluation.

 A radical trachelectomy can be performed abdominally or vaginally and there are conflicting opinions as to which is better. A radical abdominal trachelectomy with lymphadenecectomy usually only requires a 2- to 3-day hospital stay, and most women recover very quickly (approximately 6 weeks). Complications are