Cervical Cancer

Cervical cancer is a serious health concern for women worldwide. It occurs when healthy cells in the cervix, which is the narrow lower part of the uterus connecting to the vagina, undergo abnormal changes and grow uncontrollably. 

In most cases, cervical cancer develops due to a persistent infection with specific types of human papillomavirus (HPV), a common sexually transmitted virus. Understanding the causes, symptoms, and prevention strategies for cervical cancer is crucial for maintaining women's health.

What is Cervical Cancer?

Cervical cancer begins when the cells lining the cervix start to grow abnormally. These cells may gradually develop precancerous changes, known as cervical intraepithelial neoplasia (CIN) or cervical dysplasia. 

Over time, if left untreated, these abnormal cells can progress into invasive cervical cancer. The process of developing cervical cancer is usually slow, taking several years to advance from precancerous changes to cancer. However, regular screening through Pap tests and HPV testing can detect these changes early, allowing for prompt treatment and prevention of cancer development.

There are two main types of cervical cancer, classified based on the type of cell where the cancer originates (American Cancer Society, n.d.): 

• Squamous cell carcinoma: This is the most common type of cervical cancer. It develops from the flat squamous cells that cover the outer surface of the cervix (ectocervix). Squamous cell carcinoma typically begins as precancerous changes called cervical intraepithelial neoplasia (CIN) before progressing to cancer.
• Adenocarcinoma: This type of cervical cancer develops from the glandular cells that line the inner part of the cervix (endocervix). These cells produce mucus and other fluids. 
• Adenosquamous carcinoma: In rare instances, cervical cancer can have features of both squamous cell carcinoma and adenocarcinoma, known as mixed carcinoma or adenosquamous carcinoma. 

• Unusual vaginal bleeding can include bleeding between menstrual periods, after sexual intercourse, or following menopause
• Thick, foul-smelling vaginal discharge that may be tinged with blood
• Pain or discomfort during sexual intercourse (dyspareunia)
• Pelvic pain or pain in the lower back region
• Changes in menstrual periods, such as heavier flow or periods that last longer than usual

In its early stages, cervical cancer often does not cause noticeable symptoms. As the cancer progresses, however, the following signs and symptoms may appear:

• Abnormal vaginal bleeding: This may involve bleeding between menstrual periods, after sexual intercourse, or following menopause. The bleeding can be light or heavy and may occur at irregular intervals.
• Unusual vaginal discharge: Women with cervical cancer may have a watery, bloody, or foul-smelling vaginal discharge.
• Pelvic pain: As the cancer grows, it can cause pain or discomfort in the pelvic area, particularly during intercourse.
• Pain during urination: Advanced cervical cancer can spread to nearby tissues, such as the bladder, causing pain or a burning sensation while urinating.

Cervical cancer staging is determined by the extent of the tumour, lymph node involvement, and metastasis to other body parts. The stages are as follows:

• Stage 1: The cancer is limited to the cervix, without spreading to nearby tissues.
  • Stage 1A: The cancer is microscopic, with a depth of less than 5 mm into the tissue.
    • Stage 1A1: The cancer depth is less than 3 mm, and the width is less than 7 mm.
    • Stage 1A2: The cancer depth is between 3-5 mm, and the width is less than 7 mm.
  • Stage 1B: The cancer is larger than in stage 1A but still confined to the cervix.
    • Stage 1B1: The cancer size is less than 4 cm.
    • Stage 1B2: The cancer size is 4 cm or larger.
    • Stage 1B3: This classification is not widely used; cancers larger than 4 cm are typically categorised as Stage II.
• Stage 2: The cancer has extended beyond the cervix but not reached the pelvic wall.
  • Stage 2A: The cancer has spread to the upper two-thirds of the vagina but not to the parametrium (tissues surrounding the uterus).
    • Stage 2A1: The cancer is less than 4 cm in size.
    • Stage 2A2: The cancer is 4 cm or larger in size.
  • Stage 2B: The cancer has spread to the parametrium but not to the pelvic wall.
• Stage 3: The cancer has spread to the lower third of the vagina and/or the pelvic wall, and may cause kidney problems.
  • Stage 3A: The cancer has spread to the lower third of the vagina but not to the pelvic wall.
  • Stage 3B: The cancer has spread to the pelvic wall and/or causes hydronephrosis (swelling of the kidney due to blocked urine flow) or a non-functioning kidney.
• Stage 3C: The cancer involves regional lymph nodes.
• Stage 4: The cancer has spread to nearby organs or distant parts of the body.
  • Stage 4A: The cancer has spread to nearby organs, such as the bladder or rectum.
  • Stage 4B: The cancer has spread to distant organs, such as the lungs, liver, or bones.

Cervical cancer is primarily caused by persistent infection with certain high-risk types of human papillomavirus (HPV), a sexually transmitted virus. Other factors that may increase the risk of developing cervical cancer include:

• Smoking: Chemicals in tobacco can damage the DNA of cervical cells, increasing the risk of cancer.
• Weakened immune system: Conditions such as HIV/AIDS or taking immunosuppressive drugs can make it harder for the body to fight HPV infections.
• Long-term use of birth control pills: Women who have used oral contraceptives for five or more years have a slightly higher risk of cervical cancer.
• Multiple pregnancies: Women who have had three or more full-term pregnancies have an increased risk of developing cervical cancer.
• Multiple sexual partners or early sexual activity: Women who have had multiple sexual partners or who began sexual activity at a young age are at a higher risk of HPV infection, which can lead to cervical cancer.
• Chlamydia infection: Women with a history of chlamydia, a sexually transmitted bacterial infection, may have an increased risk of cervical cancer.
• Family history: Having a close family member (mother, sister) with cervical cancer may increase the risk.

Several factors can increase the risk of developing cervical cancer, including:

• Persistent infection with human papillomavirus (HPV), particularly types 16 &18
• Early sexual activity and having multiple sexual partners
• Smoking
• Women living with human immunodeficiency virus (HIV) 
• Lack of regular cervical screening 

Cervical cancer, if left untreated, can lead to serious complications that impact a woman's health and quality of life. Some of the complications include:

• Advanced cervical cancer: If cervical cancer progresses to advanced stages, it can metastasise to other parts of the body, such as the bladder, lungs, liver, or bones. This can result in severe pain, organ dysfunction, and potentially fatal consequences.
• Pain and discomfort: Advanced cervical cancer may cause chronic pain, especially in the pelvic region. Pain can significantly affect quality of life and may require ongoing management, including medication or palliative care.
• Bleeding and discharge: Women with cervical cancer may experience abnormal vaginal bleeding or discharge. This can occur between periods, after intercourse, or after menopause and may indicate advanced disease.
• Urinary and bowel issues: As the cancer progresses, it may affect nearby organs, leading to urinary problems such as incontinence or frequent urination. It can also cause bowel issues, including constipation or obstruction.
• Fertility issues: Treatment for cervical cancer, such as surgery or radiation, may impact fertility. Women of childbearing age should discuss fertility preservation options with their doctors before starting treatment.
• Treatment-related complications: The treatments for cervical cancer, including surgery, chemotherapy, and radiation, can have side effects such as fatigue, nausea, and increased risk of infection.

Cervical cancer prevention involves a multifaceted approach, including vaccination, regular screening, and lifestyle modifications. Some of the preventative measures include:

• Vaccination: The HPV vaccine is the most effective way to prevent cervical cancer. Recommended for preteens, it protects against the types of HPV that cause most cases.
• Regular screening: Routine PAP smears and HPV testing are crucial for early detection. Women should start screening at age 21, continuing every three years until age 29, and co-testing every five years or PAP alone every three years from ages 30 to 65. Even if vaccinated, regular cervical screening may still be recommended.
• Healthy diet and physical activity: Maintain a healthy diet rich in antioxidants and avoid diets high in saturated and trans fats, sugar, and sodium. Engage in regular physical activity, with at least 150 minutes of moderate activity weekly.
• Quit smoking: Avoid smoking, as it weakens the immune system and damages cellular DNA, contributing to cancer growth.
• Safe sexual practices: Practising safe sex, such as using condoms and limiting the number of sexual partners, can help reduce HPV transmission.
• Managing other risk factors: Addressing risk factors like immunosuppression and long-term hormonal contraceptive use can also aid in prevention. Women with weakened immune systems should be especially vigilant about screening and vaccination.

Early detection of cervical cancer is crucial for successful treatment and improved outcomes. Several diagnostic tests are used to identify cervical cancer:

• PAP test (Papanicolaou smear): A PAP test involves collecting cells from the cervix and examining them under a microscope for abnormalities. It is a routine screening test recommended for women aged 21 to 65.
• HPV test: This test detects the presence of high-risk human papillomavirus (HPV) strains in cervical cells. It is often used in conjunction with the Pap test for women aged 30 and above.
• Colposcopy: If abnormal cells are found during a PAP test, a colposcopy may be performed. This procedure involves using a magnifying device to examine the cervix for any visible abnormalities.
• Biopsy: If suspicious areas are identified during a colposcopy, a biopsy may be performed. This involves removing a small sample of cervical tissue for laboratory analysis to determine the presence and extent of cancerous cells.
• Imaging tests: In cases of confirmed cervical cancer, imaging tests such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans may be used to determine the stage of the cancer and assess its spread to other parts of the body.

The treatment of cervical cancer is tailored according to the stage of the disease, tumour size, lymph node involvement, histological type, and the individual’s age, reproductive wishes, and response to previous treatments. A multidisciplinary approach is typically employed, combining chemotherapy, targeted therapies, immunotherapy, and surgery or radiotherapy to eradicate cancer cells, prevent recurrence, and improve survival outcomes.

1. Cell Cycle Non-Specific Medications / Platinum Coordination Complexes

Platinum-based chemotherapy forms the cornerstone of treatment in many cervical cancer protocols.

• Cisplatin: It damages cancer cell DNA and is frequently used with radiotherapy to enhance tumour control. It is the most commonly used chemotherapy drug for cervical cancer (Yang et al., 2024)
• Oxaliplatin: It is sometimes employed in recurrent or resistant cervical cancer for its DNA-targeting effects.
• Carboplatin: An alternative to cisplatin, offering similar efficacy with a different toxicity profile, particularly in patients with kidney concerns.

2. Cell Cycle Specific Medications

These agents act on specific phases of cell division and are often combined for greater efficacy.

• Paclitaxel: It interferes with microtubule function, hindering cancer cell division and growth.
• Vinblastine: It disrupts mitotic spindles, leading to cancer cell death, particularly in combination regimens.
• 5-Fluorouracil (5-FU): It blocks DNA synthesis and is commonly used alongside radiation or other chemotherapies to enhance anti-tumour effects.

3. Target of Vascular Endothelial Growth Factor (VEGF)

Anti-angiogenic agents work by cutting off the blood supply that feeds cancer growth.

• Bevacizumab: It inhibits VEGF, slowing new blood vessel formation and tumour progression.
• Sunitinib: It is a tyrosine kinase inhibitor that blocks multiple pathways, including those promoting blood vessel growth.
• Pazopanib: It suppresses angiogenesis and may be used in metastatic or recurrent disease settings.

4. Target of Epidermal Growth Factor Receptor (EGFR)

These agents block growth signals within cancer cells.

• Cetuximab: A monoclonal antibody that targets EGFR, slowing down cancer proliferation.
• Lapatinib: A dual EGFR and HER2 inhibitor, used in cases with overexpression of these receptors.
• Gefitinib: It blocks EGFR-related pathways involved in tumour growth and invasion.
• Erlotinib: It is effective in select patients with EGFR-positive tumours and may be used when standard options are limited.

5. Monoclonal Antibody Medication

Immunotherapy is emerging as a powerful tool in managing advanced cervical cancer.

• Pembrolizumab: It is a cancer immunotherapy medication that enhances the body’s ability to recognise and destroy cancer cells. It is particularly useful in recurrent or metastatic cervical cancer, especially in patients whose tumours express PD-L1.

Living with cervical cancer involves several important considerations to ensure the best possible outcome and quality of life. These include:

• Attend regular checkups and undergo tests, such as blood tests, X-rays, and scans, to monitor the cancer's progression and detect any recurrence early.
• Seek treatment to relieve symptoms and improve quality of life, especially in advanced cases. This can include palliative care and supportive therapies.
• Reach out to family, friends, or support groups to help cope with the emotional challenges of living with cervical cancer.
• Adopt a healthy lifestyle, including a balanced diet, regular exercise, and stress reduction techniques, to support overall well-being during and after treatment.
• Discuss fertility options with your doctor, as some treatments may impact your ability to have children in the future.

If you experience any symptoms that could be associated with cervical cancer, such as abnormal vaginal bleeding, pelvic pain, or pain during intercourse, it's essential to consult your doctor promptly. Additionally, if you have been diagnosed with cervical cancer and notice any new or worsening symptoms, such as persistent pain, heavy bleeding, urinary or bowel symptoms, leg swelling, unexplained weight loss, or new neurological symptoms, contact your doctor immediately.

• Cervical cancer is a type of cancer that develops in the cells of the cervix, the lower part of the uterus that connects to the vagina.

• The primary cause of cervical cancer is persistent infection with certain types of human papillomavirus (HPV).

• Symptoms of cervical cancer may include abnormal vaginal bleeding, pelvic pain, and pain during intercourse, but early-stage cervical cancer often has no noticeable symptoms.

• Treatment options for cervical cancer include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy, depending on the stage of the cancer and individual patient factors.

• Regular cervical screening (PAP smear tests) and HPV vaccination are key strategies for preventing cervical cancer.

• Living with cervical cancer involves regular follow-up care, symptom management, emotional support, lifestyle changes, and fertility considerations.