Cancer Type

cervical cancer Introduction

Cervical cancer ranks eighth among the most common cancers among women in Hong Kong. According to data from the Hong Kong Cancer Registry, 520 new cases were recorded in 2019; in the same year, 162 people died from cervical cancer, making it the eighth leading cause of cancer death among women in Hong Kong. Generally speaking, women over 30 years of age have a higher risk of developing cervical cancer, and the median age of diagnosis for cervical cancer in Hong Kong is approximately 55 years old.Therefore, understandingthe causes, staging, diagnostic methods, andtreatment optionsofcervical canceris crucial for women's prevention of this cancer.

Persistent infection with certain types of human papillomavirus (HPV)isa majorcause ofcervical cancer. HPV is a common virus that is sexually transmitted; at least half of all sexually active people have been infected with HPV at some point in their lives, but only a small percentage of women will develop cervical cancer as a result. Cervical cancer can be effectively prevented through screening and the HPV vaccine. The earlier the cancer is detected, the higher the chance of a cure and the better the patient's quality of life can be maintained.

I. Types of Cervical Cancer

Risk factors for cervical cancer

Cervical cancer stage	Five-year survival rate
Issue 1	95％
Issue 2	70％
Issue 3	40％
Issue 4	15％

Symptoms of cervical cancer

Early-stage cervical cancer often presents with few or no symptoms. However, if it progresses to an advanced stage or spreads to other parts of the body, the condition may worsen. Common symptoms include:

- Spotting or light bleeding after or between periods
- Long menstrual period and heavy bleeding
- Bleeding after sexual intercourse, douching, or pelvic examination
- Increased vaginal discharge
- Pain during sexual intercourse
- Postmenopausal bleeding
- Unexplained persistent pelvic and/or back pain

ii. Risk factors for cervical cancer

HPV infection and causes of cervical cancer

Human papillomavirus (HPV) infection is a major cause of cervical cancer. There are over 150 different HPV virus combinations that can cause various conditions. Low-risk HPV viruses (mostly types 6 and 11) do not develop into cancer but can cause genital warts and respiratory papillomas. High-risk HPV viruses, however, can cause cancer. Studies show that over 40 types of HPV viruses can be transmitted through sexual contact, leading to precancerous lesions and cancers of the cervix, vagina, vulva, and anus.

There are 13 types of HPV viruses that cause cervical cancer, with types 16 and 18 being most strongly associated with it, accounting for about 70% of all cases. In Hong Kong, cervical cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58 accounts for about 90%. Most HPV viruses that infect the reproductive organs can be cleared by the body's own immune system, but if the cervix remains infected, the cells can mutate, evolving into cervical intraepithelial neoplasia, which may develop into cervical cancer over time.

Besides HPV infection, the following factors can also increase a woman's risk of cervical cancer:

Having HIV or other immune system diseases
Having a smoking habit
Long-term use of birth control pills (five years or more).
Having given birth to three or more children
Having multiple or non-fixed sexual partners

Understanding the causes and risk factors of cervical cancer and discussing them with your doctor can help you make more informed lifestyle and healthcare choices, reducing your risk of developing cervical cancer.

III. Diagnostic methods for cervical cancer

Cervical cancer screening

Diagnostic methods for cervical cancer typically include HPV testing and a cervical cytology test (also known as a Pap smear). During screening, healthcare professionals insert a speculum into the vagina and use a sampling brush to collect a sample from the surface of the cervix for testing. The HPV test detects whether cervical cells are infected with high-risk types of HPV; while the Pap smear detects abnormalities in cervical cells. If lesions are found in the cells, further examination, such as a biopsy, is usually scheduled.

Scientific evidence has confirmed that regular cervical screening is an effective diagnostic method for preventing cervical cancer. Women aged 25 to 64 who have had sexual experience should undergo regular cervical screening, even if they have no symptoms.

Cervical cancer diagnostic methods

If a doctor suspects a patient has cervical cancer, they will perform a thorough examination of the cervix. The diagnostic process for cervical cancer involves using a colposcope to examine for abnormal cells and performing a biopsy to obtain cervical tissue for pathological examination. Biopsy methods include:

Biopsy

An abnormal tissue is removed from the cervix using an electrically heated loop coil and then sent for testing. This is usually performed under local anesthesia.

Loop Electrosurgical Excision Procedure (LEEP)

The doctor will use instruments to collect a small sample of cervical tissue for testing. In some cases, the doctor may also remove a cone-shaped section of the cervix for testing under general anesthesia.

Cervical curettage

Use a small curette or fine brush to scrape tissue samples from the cervix for testing.

If a biopsy reveals cancer cells in the cervical tissue, the patient may need to undergo further examinations, such as X-rays, CT scans, MRI scans, and positron emission tomography (PET) scans, to confirm the stage of cancer and whether the cancer cells have spread beyond the cervix.

IV. Cervical Cancer Staging

Cervical cancer can be staged into four stages: Stage 1 through Stage 4.

Issue 1

Cancer cells have invaded the subcutaneous tissue from the surface of the cervix, but remain confined to the cervix.

Issue 2

The cancer has spread to the tissues surrounding the cervix and the upper two-thirds of the vagina, but has not yet spread to the pelvic wall or the lower part of the vagina.

Issue 3

The cancer cells have spread to the bladder, rectum, or other distant organs of the body, such as the lungs or bones.

Issue 4

The cancer cells have metastasized to distant organs, such as the liver, lungs, bones, and brain.

V. Treatment methods for cervical cancer

Treatment for cervical cancer depends on factors such as tumor size, location, stage, extent of spread, patient age, tolerance for surgical and anesthesia risks, and fertility desires. Early-stage cervical cancer is generally confined to the cervix and can be treated surgically with a high chance of cure. In advanced stages, if the cancer has spread to other organs, it is difficult to remove all cancer cells surgically. Doctors typically employ systemic treatments, such as chemotherapy, to control further spread. The following are various treatment methods for cervical cancer:

Surgical resection

There are three main types of cervical cancer surgery:

- Cervical excision surgery：This procedure involves removing part or all of the cervix, surrounding tissue, and the upper part of the vagina, but the uterus is preserved. This surgery can preserve a woman's fertility, but it is only suitable for very early-stage cervical cancer.
- Hysterectomy：The procedure involves removing the cervix and uterus, and depending on the stage of the cancer, the ovaries and fallopian tubes may also need to be removed. Hysterectomy is the most common treatment for early-stage cervical cancer.
- Pelvic organ removal surgery: This procedure is typically performed when cervical cancer recurs. It involves the removal of all organs within the pelvic cavity, including the cervix, vagina, uterus, ovaries, fallopian tubes, bladder, and rectum.
  
  Complications of this surgery include infection, bleeding, and accidental injury to the ureter/bladder or rectum leading to difficulty in urination or defecation. Long-term complications may include lymphedema, vaginal bleeding, and infertility.

Radiotherapy

Radiation therapy (commonly known as electrotherapy) uses high-energy radiation to kill cancer cells. At different stages of cervical cancer, radiation therapy can be used alone or in combination with other treatments such as surgery and chemotherapy. It can also be used to treat cervical cancer that has spread or recurred after treatment. The most common types of radiation therapy used to treat cervical cancer include:

External beam radiation therapy (EBRT)

External beam radiation therapy (EMB) uses an electrotherapy device to deliver X-rays to the tumor site from outside the body. Each treatment session lasts only a few minutes and is painless. As one of the main treatment methods for cervical cancer, ERB is sometimes used in conjunction with chemotherapy; if the cancer has not spread to distant areas, brachytherapy, also known as internal radiation therapy, can be performed after concurrent chemoradiotherapy.

Side effects of external beam radiation therapy include fatigue, stomach upset, diarrhea or loose stools, nausea and vomiting, mild redness or peeling of the skin, radiation cystitis, vaginal pain, menstrual changes, anemia, and thrombocytopenia. If chemotherapy is administered concurrently with radiation therapy, the levels of red blood cells, white blood cells, and platelets in the blood may be lower, potentially exacerbating fatigue and nausea. However, these side effects usually improve within weeks after treatment is discontinued.

Internal radiation therapy (brachytherapy)

Internal radiation therapy involves placing a radiation source inside or near the cancer. In cervical cancer treatment, the radiation source is placed inside the vagina or cervix. Internal radiation therapy is mostly used in conjunction with external radiation therapy to treat cervical cancer, and is only used alone in rare cases (usually in more specific early-stage cervical cancer cases).

Internal radiation therapy can be divided into high-dose and low-dose types. High-dose internal radiation therapy involves placing radioactive material through the vagina at the target location for several minutes, after which it is removed; hospitalization is not required. Low-dose internal radiation therapy requires placement for several days, during which time the patient must lie in bed and have the radioactive material fixed by a device, thus requiring hospitalization. However, because the radiation source is close to the body, patients may experience side effects such as vaginal redness and pain due to irritation, and bladder irritation.

Radiation therapy can cause long-term radiation-related side effects, including: vaginal stenosis, vaginal dryness, rectal bleeding or narrowing, the formation of an abnormal passage (or fistula) between the rectum and vagina leading to fecal incontinence, urinary problems, a fistula between the bladder and vagina, fragile bones, and leg swelling. If any abnormalities occur, please consult a doctor.

Chemotherapy

Chemotherapy drugs are mostly administered intravenously or orally and can kill cancer cells in most parts of the body. Not all cervical cancer patients need chemotherapy, but chemotherapy helps radiation therapy to work more effectively, so in some cases radiation therapy and radiotherapy are performed together. However, for patients whose cancer cells have spread or have recurred after treatment, chemotherapy is the main treatment for this type of cervical cancer, and often multiple chemotherapy drugs are used in combination.

Chemotherapy is administered in cycles, with rest periods in between to allow patients to recover from the effects of the medication. Each chemotherapy session typically lasts one to three weeks, depending on the specific drug used.

Chemotherapy drugs kill cancer cells, but they also damage the body's normal cells, causing certain side effects. The type and dosage of the drug, as well as the duration of treatment, determine the side effects. Most side effects are short-term and disappear after treatment ends, but some can persist for a long time, even permanently. Common short-term side effects of chemotherapy include nausea and vomiting, loss of appetite, hair loss, mouth ulcers, and fatigue. Because chemotherapy damages the bone marrow's blood-forming cells, blood cell counts may decrease, increasing the risk of infection and causing anemia.

Potential long-term side effects of chemotherapy include menstrual changes, premature menopause and infertility, and neuropathy. For young female patients who have not had their uterus removed, menstrual changes are a common side effect of chemotherapy, but pregnancy is still possible even if menstruation stops during chemotherapy. However, pregnancy during chemotherapy is not safe, as it can lead to birth defects and interfere with treatment. Patients who have completed treatment can usually continue to have children, but this should be discussed with a doctor first.

Targeted therapy

Targeted therapy uses drugs that target or target proteins on cervical cancer cells, aiming to destroy the cancer cells or slow their growth. There are several types of targeted drugs suitable for cervical cancer; among them, angiogenesis inhibitors prevent vascular endothelial growth factor (VEGF) from functioning, thus preventing tumors from forming new blood vessels to obtain the nutrients they need for growth.

Angiogenesis inhibitors are currently used to treat advanced cervical cancer as one of its treatment methods. Common side effects of these drugs include high blood pressure, fatigue, and nausea. Less common but more serious side effects include bleeding, blood clots, wound healing problems, and heart failure. The drugs may also cause fistulas between the vagina and part of the colon or intestines, or cause intestinal perforation, but these are rare.

Antibody-drug conjugates (ADCs) are another type of targeted therapy for cervical cancer, consisting of monoclonal antibodies associated with chemotherapy drugs. These drugs target the tissue factor (TF) protein on cancer cells, delivering the chemotherapy drugs directly to the cancer cells by attaching to the TF protein. This type of drug can be used to treat metastatic cervical cancer, or cervical cancer that has recurred after initial treatment but has not responded to at least two other medications.

Common side effects of antibody-drug conjugates include fatigue, nausea, hair loss, vomiting, bleeding, diarrhea, rash, and peripheral neuropathy. The drug may cause low red and white blood cell counts, and kidney function may also be abnormal. Another major side effect is eye problems; people taking this drug may experience dry eye, vision changes, decreased vision, or corneal ulcers. Regular eye exams are recommended.

Immunotherapy

Immunotherapyuses medication to stimulate the body's own immune system, enabling cells to more effectively recognize and destroy cancer cells. Immunotherapy can be used to treat cervical cancer that has spread or recurred.

A crucial function of the immune system is to prevent itself from attacking the body's normal cells. However, cancer cells can utilize the PD-1 immune checkpoint to prevent the body's T cells from attacking other cells, thus allowing the cancer cells to continue growing. Immunotherapy drugs that inhibit PD-1 can effectively enhance the immune system's immune response against cancer cells, shrinking tumors or slowing their growth. However, before administering these drugs, it is necessary to test whether the patient has sufficient PD-L1 protein expression.

Side effects of immunotherapy include fatigue, fever, nausea, headache, rash, loss of appetite, constipation, joint or muscle pain, and diarrhea. In addition, the basic function of these drugs is to eliminate the body's immune system's ability to recognize them, and sometimes there can be side effects where the immune system attacks other parts of the body, such as causing serious problems with the lungs, intestines, liver, kidneys, or other organs, although these serious side effects are rare.

VII. Follow-up after cervical cancer treatment

Even after completing treatment, cervical cancer patients still need close monitoring from their doctors and undergo necessary follow-up examinations, including laboratory tests or other imaging studies, to check for signs of cancer or treatment side effects. If any suspicious symptoms or results are found during these examinations, further testing may be required.

Generally, cervical cancer patients are scheduled for frequent follow-up appointments immediately after completing treatment. Most doctors then recommend follow-up appointments every three to six months, gradually reducing the frequency thereafter. Any cancer treatment can have side effects, some of which may last a long time, and some may not appear until years after treatment is completed. Therefore, regular follow-up appointments ensure that patients receive timely treatment.

Regardless of the type of treatment received, most doctors recommend that patients undergo regular Pap smears after cervical cancer treatment to diagnose any recurrence. Patients who have completed treatment should also maintain healthy lifestyle habits, including a healthy diet, regular exercise, and maintaining a healthy weight. After treatment, patients and their doctors can discuss and develop a rehabilitation care plan, which includes a suggested schedule for follow-up examinations, a list of possible tests, instructions for re-examination, and dietary and exercise recommendations. A rehabilitation care plan helps patients understand their rehabilitation path and strengthens their confidence in a full recovery.

For information on the actual costs of various chemotherapy treatments for cervical cancer, as well as recommendations on combining several treatment methods (such as treatment after breast cancer surgery), please consult the United Cancer Centre Hong Kong.

FAQ

1. What is cervical cancer?

Cervical cancer is a cancer caused by the uncontrolled and abnormal proliferation of cervical cells, primarily associated with persistent infection with high-risk human papillomavirus (HPV). It is the eighth most common cancer among women in Hong Kong, frequently occurring in women over 30 years of age, with a median age of diagnosis of approximately 55.

2. What are the common symptoms of cervical cancer?

Early-stage cervical cancer may not present with obvious symptoms, but as the disease progresses, the following symptoms may appear:

Bleeding between periods or after sexual intercourse,
abnormally increased or foul-smelling vaginal discharge,
pain during intercourse, persistent
vaginal bleeding after menopause,
and unexplained pelvic or back pain.

If you experience any of the above symptoms, consult a doctor as soon as possible.

3. What causes cervical cancer? What factors increase the risk of developing cervical cancer?

The main causes of cervical cancer include:

Persistent infection with high-risk HPV types (such as types 16 and 18)
smoking
multiple sexual partners or active sexual behavior,
long-term use of birth control pills (more than five years),
compromised immune system (such as HIV infection),
multiple births (three or more).

4. What are the diagnostic methods for cervical cancer?

The main diagnostic methods for cervical cancer include:

HPV testing: Screens for infection with high-risk HPV viruses.
Cervical cell examination (Pap smear): Detects abnormal lesions in cervical cells.
Biopsy: When screening results are abnormal, the doctor will take further samples for testing.

Women aged 25 to 64 who have had sexual intercourse are advised to undergo regular screening.

5. What are the different stages of cervical cancer?

Cervical cancer can be divided into four stages:

Stage 1: Cancer cells are confined to the cervix.
Stage 2: Cancer cells spread to tissues surrounding the cervix but not to the pelvic wall.
Stage 3: Cancer cells affect the pelvic wall, bladder, or rectum.
Stage 4: Cancer cells metastasize to distant organs, such as the liver or lungs.

6. What are the treatment options for cervical cancer?

Treatment methods for cervical cancer vary depending on the stage of the disease and the patient's condition, and include:

Surgery: such as hysterectomy, suitable for early-stage patients. Radiation therapy
Radiotherapy: uses radiation to destroy cancer cells, suitable for mid-stage and some late-stage patients.
Chemotherapy: suitable for late-stage or recurrent patients, often used in conjunction with radiotherapy.
Targeted therapy: precise treatment targeting specific proteins or molecules, suitable for late-stage patients.
Immunotherapy: enhances the immune system's attack on cancer cells.

7. How to prevent cervical cancer?

Effective measures to prevent cervical cancer include:

HPV vaccination: Recommended for women aged 9-26. The vaccine is most effective for those who have never had sexual intercourse.
Avoid smoking: Smoking increases the risk of infection
Safe sexual practices: Avoid having multiple sexual partners and always use condoms to reduce the risk of HPV infection.
Regular cervical screening: Women aged 25-64 should have a Pap smear or HPV test every three years.