Cervical cancer

Cervical cancer is a common type of cancer in women. It occurs when cancerous (malignant) cells develop in the tissues of the cervix.

The uterus is a hollow, inverted, pear-shaped organ where a fetus develops during pregnancy. The cervix, or cervical canal, is the lower part of the uterus that connects it to the vagina (birth canal).

Cervical cancer begins to grow slowly from mutated cancer cells in the most superficial layer of cervical tissue, called the epithelium or mucosa. Before cancer cells develop, normal cervical tissue undergoes a process known as dysplasia, during which abnormal, mutated cells start to appear.

A diagnostic test called the Pap smear (or Pap test) is often used to detect these precancerous cells.

If untreated, the cancer cells may grow, spread, and infiltrate deeper into the cervix and surrounding tissues.

The cervix can be divided into two parts, each lined with different types of cells:

• Endocervix: This is the portion closest to the uterus, lined with glandular cells.
• Exocervix: This is the portion closest to the vagina, visible during colposcopy or Pap smear procedures. It is lined with squamous cells, also known as stratified squamous epithelium.

The area where these two parts meets is called the transformation zone, where the two types of cells coexist. The location of the transformation zone changes over time due to factors such as age and childbirth.

Cervical cancer originates in the transformation zone. This is where the endocervix and exocervix meet, and the stratified squamous epithelium of the exocervix transitions to the simple glandular columnar epithelium of the endocervix.

This area is particularly vulnerable to changes caused by microorganisms, such as the human papillomavirus (HPV), as well as physical or chemical agents like tobacco. These factors can induce cellular changes and mutations, leading to a condition known as dysplasia, which may eventually develop into cervical cancer.

Nearly all cervical cancers are caused by the human papillomavirus (HPV), which is primarily spread through sexual contact. There are more than 150 types of HPV, but 12 are considered high-risk or carcinogenic. These include the following genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59.

Other HPV types can cause common warts or genital warts, but they are not linked to cervical cancer.

Additional risk factors for cervical cancer include:

• Having HIV (human immunodeficiency virus): HIV causes AIDS and weakens the immune system, reducing the body’s ability to fight infections and diseases.
• Smoking.
• Long-term use of oral contraceptives (for five years or more).
• Multiple childbirths.
• Multiple sexual partners.

The most common types of cervical cancer are:

• Squamous cell carcinoma: Accounts for about 90% of cases. It develops in the transformation zone from the squamous cells of the exocervix.
• Adenocarcinoma: Arises from the glandular cells of the endocervix.

Less common types include:

• Adenosquamous carcinoma (mixed carcinoma): Contains features of both squamous cell carcinoma and adenocarcinoma.
• Melanoma, sarcoma, or lymphoma: Rare types of cervical cancer.

Identifying the specific type of cervical cancer is crucial because the tumor's behavior, prognosis, and treatment vary depending on the subtype. These differences affect the choice of chemotherapy, as well as the planning of surgery and radiotherapy.

Cervical cancer often does not cause symptoms in its early stages.

As the cancer progresses, the following symptoms may appear:

• Metrorrhagia or intermenstrual bleeding: Abnormal vaginal bleeding that occurs between normal menstrual cycles.
• Watery vaginal discharge: May have a strong odor or contain traces of blood.
• Pelvic pain or dyspareunia: Pain during sexual intercourse.

Cervical cancer often does not cause symptoms in its early stages, so a series of tests are typically necessary for diagnosis:

• Cervical cytology (Pap smear or Papanicolaou test): This test is performed during a speculoscopy or colposcopy procedure, which allows the doctor to visualize the vaginal canal and cervix. Using a cotton swab, brush (cytobrush), or small wooden spatula, the doctor gently scrapes cells from the cervix (including the exocervix and the outer part of the endocervix) to collect a sample. The procedure may cause mild pressure or discomfort, and in some cases, slight pain. The collected sample is stained with special dyes (e.g., Harris hematoxylin and eosin) and examined under a microscope to detect abnormalities or microorganisms.
• HPV test: This test detects the presence of high-risk types of the human papillomavirus (HPV), which can cause cell changes leading to cervical cancer.
• Biopsy: If abnormal cells are found, a biopsy may be necessary. A tissue sample is taken from the cervix and analyzed under a microscope to confirm the presence of cancer cells. Types of biopsies include:
  • LEEP (Loop Electrosurgical Excision Procedure): Uses a thin wire loop to remove a superficial portion of cervical tissue.
  • Conization: Removes a cone-shaped portion of deeper cervical tissue for more detailed examination.

The prognosis (chances of recovery) and choice of treatment depend on the stage of the cancer (localized or metastatic) and the patient’s overall health.

Once a diagnosis is made, additional tests are used to determine the stage of the cancer and evaluate its spread. Transvaginal and abdominal ultrasounds, chest X-rays, and CT scans of the abdomen and chest help assess whether the tumor is confined to the cervix or has metastasized to other organs.

To determine the stage of cervical cancer, a physical examination, imaging studies, and possibly biopsies are required. The stages are classified as follows:

Stage I: Cancer is confined to the cervix and has not spread to other parts of the body. It is further divided into:

• Stage IA: Diagnosed only by microscopic examination.
  • Stage IA1: Cancerous area is less than 3 mm deep.
  • Stage IA2: Cancerous area is 3 to 5 mm deep.
• Stage IB: Tumor is larger but still confined to the cervix.
  • Stage IB1: Tumor measures more than 5 mm deep and less than 2 cm wide.
  • Stage IB2: Tumor measures more than 2 cm deep and less than 4 cm wide.
  • Stage IB3: Tumor is more than 4 cm wide.

Stage II: Cancer has spread beyond the cervix to nearby areas (such as the uterus or vagina) but remains within the pelvic region:

• Stage IIA: Tumor is confined to the upper two-thirds of the vagina and does not involve the parametrial region:
  • Stage IIA1: Tumor is less than 4 cm wide.
  • Stage IIA2: Tumor is more than 4 cm wide.
• Stage IIB: Tumor has spread to the parametrial region but not to the pelvic wall.

Stage III: Cancer has extended to the lower third of the vagina, the pelvic wall, or affects the kidneys, but there is no distant spread:

• Stage IIIA: Tumor involves the lower third of the vagina but not the pelvic wall.
• Stage IIIB: Tumor has reached the pelvic wall and/or affects kidney function.
• Stage IIIC: Tumor has spread to regional lymph nodes.
  • Stage IIIC1: Cancer involves pelvic lymph nodes.
  • Stage IIIC2: Cancer involves para-aortic lymph nodes.

Stage IV: Cancer has spread to distant parts of the body:

• Stage IVA: Cancer has invaded nearby organs, such as the bladder or rectum, but has not spread to distant areas.
• Stage IVB: Cancer has metastasized to distant organs, such as the lungs.

Recurrent cervical cancer. Recurrent disease means that the cancer has returned after treatment. It may reappear in the cervix or metastasize to another part of the body.

There are various treatment options available for all patients with cervical cancer, depending on the stage and specific characteristics of the cancer. These treatments include:

• Surgery: Removal of cancerous tissue through an operation.
• Radiotherapy: Use of high-energy radiation to destroy cancer cells.
• Sentinel lymph node biopsy: During surgery, lymph nodes in the pelvis that are most likely to contain cancer are removed to check for cancer spread.
• Immunotherapy: Medications that stimulate the immune system to recognize and attack cancer cells.
• Targeted therapy: Drugs that target specific proteins involved in cancer growth. For example:
  • Bevacizumab: Currently used to treat advanced cervical cancer.
  • Cediranib and nintedanib: Other drugs under investigation for advanced cases.
• Chemotherapy: Drugs used to kill cancer cells.

Treatment decisions are based on factors such as the tumor's size, spread, and involvement with surrounding tissues and lymph nodes. In some cases, surgery options include:

• Cryosurgery: Removal of cancer by freezing the tissue.
• Laser surgery: Use of an intense beam of light to kill cancer cells.
• Conization: Removal of a cone-shaped piece of tissue from the cervix. This is often used for biopsies and early-stage cervical cancer treatment.
• Electrosurgical excision (LEEP): Uses an electric current passed through a thin wire loop to excise abnormal tissue.
• Hysterectomy: Removal of the uterus and cervix, as well as cancerous tissue.
  • Vaginal hysterectomy: Removal of the uterus through the vagina.
  • Abdominal hysterectomy: Removal of the uterus through an incision in the abdomen. It may also involve removal of the ovaries and fallopian tubes (bilateral salpingo-oophorectomy).
  • Radical hysterectomy: Removal of the cervix, uterus, and part of the vagina, along with lymph nodes in the area.
• Pelvic exenteration: If cancer has spread beyond the cervix or female organs, it may be necessary to remove the lower colon, rectum, or bladder, along with the cervix, uterus, and vagina. This procedure may require reconstructive surgery, such as vaginoplasty, to create an artificial vagina.