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.

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.

Causes

Infection with some types of human papilloma virus (HPV) is the greatest risk factor for cervical cancer, followed by smoking. Other risk factors include human 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 type 16 and 18 are the cause of 70% of cervical cancer globally while 31 and 45 are the cause of another 10%.

Women who have many sexual partners (or who have sex with men who have had many other partners) have a greater risk.

High-risk types HPV (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 low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81)

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.

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 of condoms 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 glens penis, and cleaning of this area may be preventative.

Smoking

Smoking has also been linked to the development of cervical cancer. There are a few different ways that smoking can increase the risk of cervical cancer in women which can be by direct and indirect methods of inducing cervical cancer.

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, Spira Brush CX, Soft Biopsy or Soft-ECC.

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.

Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatment.

Cancer Subtypes

Histologic subtypes of invasive cervical carcinoma include the following: Though squamous cell carcinoma is the cervical cancer with the most incidences, 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

Treatment

Treatment options for cervical cancer by stage

The stage of a cervical cancer is the most important factor in choosing treatment. However, other factors that affect this decision include the exact location of the cancer within the cervix, the type of cancer (squamous cell or adenocarcinoma), your age, your overall physical condition, and whether you want to have children.

Stage 0 (carcinoma in situ)

Treatment options for squamous cell carcinoma in situ are the same as for other pre-cancers (dysplasia or cervical intraepithelial neoplasia [CIN]). Options include cryosurgery, laser surgery, loop electrosurgical excision procedure (LEEP/LEETZ), and cold knife conization.

For adenocarcinoma in situ, hysterectomy is usually recommended. For women who wish to have children, treatment with a cone biopsy may be an option. The cone specimen must have no cancer cells at the edges, and the patient must be closely watched. After the woman has finished having children, a hysterectomy is recommended.

A simple hysterectomy is also an option for treatment of squamous cell carcinoma in situ, and might be done if it returns after other treatments. All cases of CIS can be cured with appropriate treatment. However, pre-cancerous changes can recur (come back) in the cervix or vagina, so it is very important for your doctor to watch you closely. This includes follow-up with regular Pap tests and in some instances with colposcopy.

Stage IA is divided into stage IA1 and stage IA2

Stage IA1: For this stage you have 3 options

  • If you still want to be able to have children, first the cancer is removed with a cone biopsy, and then you are watched closely to see if the cancer comes back.
  • If the cone biopsy doesn’t remove all of the cancer (or if you are done having children), the uterus will be removed (hysterectomy).
  • If the cancer has invaded the blood vessels or lymph vessels, you might need a radical hysterectomy along with removal of the pelvic lymph nodes. For women who still want to be able to have children, a radical trachelectomy can be done instead of the radical hysterectomy.

Stage IA2: There are 3 treatment options:

  • Radical hysterectomy along with removal of lymph nodes in the pelvis
  • Brachytherapy with or without external beam radiation therapy to the pelvis
  • Radical trachelectomy with removal of pelvic lymph nodes can be done if you still want to be able to have children

If the cancer is found in any pelvic lymph nodes during surgery, some of the lymph nodes that lie along the aorta (the large artery in the abdomen) may be removed as well. Any tissue removed at surgery will be examined in the laboratory to see if the cancer has spread further than expected. If the cancer has spread to the tissues next to the uterus (called the parametria) or to any lymph nodes, radiation therapy is usually recommended. Often chemotherapy will be given with the radiation therapy. If the pathology report says that the tumor had positive margins, this means that some cancer might have been left behind. This is also treated with pelvic radiation (given with cisplatin chemotherapy). The doctor may advise brachytherapy, as well.

Stage IB is divided into stage IB1 and stage IB2

Stage IB1: There are 3 options available:

  • The standard treatment is a radical hysterectomy with removal of lymph nodes in the pelvis. Some lymph nodes from higher up in the abdomen (called para-aortic lymph nodes) are also removed to see if the cancer has spread there. If cancer cells are found in the edges of the tissues removed (positive margins) or if cancer cells are found in lymph nodes during this operation, radiation therapy may be given, possibly with chemotherapy, after surgery.
  • The second treatment option is radiation with both brachytherapy and external beam radiation therapy.
  • Radical trachelectomy with removal of pelvic (and some para-aortic) lymph nodes is an option if the patient still wants to be able to have children

Stage IB2: There are 3 options available

  • The standard treatment is the combination of chemotherapy with cisplatin and radiation therapy to the pelvis plus brachytherapy.
  • Another choice is radical hysterectomy with removal of pelvic (and some para-aortic) lymph nodes. If cancer cells are found in the lymph nodes removed, or in the margins, radiation therapy may be given, possibly with chemotherapy, after surgery.
  • Some doctors advise radiation given with chemotherapy (first option) followed by a hysterectomy.
Stage II is divided into stage IIA and stage IIB
  • One choice for treatment is brachytherapy and external radiation therapy. This is most often recommended if the tumor is larger than 4 cm (about 1½ inches). Chemotherapy with cisplatin will be given along with the radiation.
  • Some experts recommend removing the uterus after the radiation therapy is done.
  • If the cancer is not larger than 4 cm, it may be treated with a radical hysterectomy and removal of lymph nodes in the pelvis (and some in the para-aortic area). If the tissue removed at surgery shows cancer cells in the margins or cancer in the lymph nodes, radiation treatments to the pelvis will be given with chemotherapy. Brachytherapy may be given as well.

Stage IIB: Combined internal and external radiation therapy is the usual treatment. The radiation is given with the chemotherapy drug cisplatin. Sometimes other chemo drugs may be given along with cisplatin.

Stage III and IVA

Combined internal and external radiation therapy given with cisplatin is the recommended treatment.

If cancer has spread to the lymph nodes (especially those in the upper part of the abdomen) it can be a sign that the cancer has spread to other areas in the body. Some experts recommend checking the lymph nodes for cancer before giving radiation. One way to do this is by surgery. Another way is to do a CT or MRI scan to see how big the lymph nodes are. Lymph nodes that are bigger than usual are more likely to have cancer. Those lymph nodes can be biopsied to see if they contain cancer. If lymph nodes in the upper part of the abdomen (the para-aortic lymph nodes) are cancerous, doctors may want to do other tests to see if the cancer has spread to other parts of the body.

Stage IVB

At this stage, the cancer has spread out of the pelvis to other areas of the body. Stage IVB cervical cancer is not usually considered curable. Treatment options include radiation therapy to relieve the symptoms of cancer that has spread to the areas near the cervix or to distant sites (such as the lungs or bone). Chemo is often recommended. Most standard regimens use a platinum compound (such as cisplatin or carboplatin) along with another drug such as paclitaxel (Taxol), gemcitabine (Gemzar), or topotecan. Clinical trials are testing other combinations of chemo drugs, as well as some other experimental treatments.

Recurrent Cervical Cancer

Cancer that comes back after treatment is called recurrent cancer. Cancer can come back locally (in the pelvic organs near the cervix) or come back in distant areas (spread through the lymphatic system and/or the bloodstream to organs such as the lungs or bone).

If the cancer has recurred in the pelvis only, extensive surgery (by pelvic exenteration) may be an option for some patients. This operation may successfully treat 40% to 50% of patients. Sometimes radiation or chemotherapy may be used for palliative treatment (treatment to relieve symptoms but not expected to cure).

If your cancer has recurred in a distant area, chemo or radiation therapy may be used to treat and relieve specific symptoms. If chemo is used, you should understand the goals and limitations of this therapy. Sometimes chemo can improve your quality of life, and other times it can diminish it. You need to discuss this with your doctors. Fifteen percent to 25% of patients may respond at least temporarily to chemo.

New treatments that may benefit patients with distant recurrence of cervical cancer are being evaluated in clinical trials.

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.

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