Cervical Cancer

Cervical cancer was the seventh most common female cancer in Hong Kong and accounted for 3.1% of all new female cancer cases in 2021. In 2021, 596 new cases of cervical cancer were diagnosed and the crude incidence rate was 14.8 per 100,000 female population.  Meanwhile, the age-standardised incidence rate was 8.1 per 100,000 standard population.

Cervical cancer is also the eighth leading cause of female cancer deaths in Hong Kong. In 2021, a total of 178 women died from this cancer, accounting for 2.8% of female cancer deaths.

In the past few decades (1983-2021), a downward trend was observed for both incidence and mortality of cervical cancer. This decrease was probably due to HPV vaccination.

Almost all cervical cancers are caused by persistent infection with one of the cancer-causing (or high-risk) human papillomavirus (HPV) types. Risk factors for HPV infection or cervical cancer include:

• Multiple sexual partners
• Sexual intercourse at an early age
• Co-infection with sexually transmitted diseases
• Smoking
• Weakened immunity
• Chronic renal diseases
• Long-term use of oral contraceptive pills for more than 5 years (the risk returns to normal after 10 years of stopping use)
• High number of childbirths or young age at first pregnancy
• Socioeconomic factors

Cervical cancer in its early stage may not present any symptoms at all. If you notice the following, you should consult your doctor and undergo examinations as soon as possible:

• Abnormal vaginal bleeding, such as between periods or after sexual intercourse
• Vaginal bleeding after menopause
• Bleeding after douching or pelvic examination
• Blood-tinged vaginal discharge
• Foul smelling vaginal discharge
• Pain during sexual intercourse
• Unexplained, persistent pelvic pain
• Backache, swollen feet or difficulty in passing stool may occur in the advanced stage of cervical cancer

A doctor would typically order the following examinations for suspected cervical cancer patients.

• Cervical cancer screening or “Pap smear test”: 
  • A non-distressful procedure requiring only a few minutes. Follow-up procedures will be necessary if abnormal changes or cancerous cells are detected.

• Colposcopy: 
  • If your Pap smear result shows abnormal cells or HPV test is positive, you will have colposcopy.
  • During the procedure, you will lie on the bed same as doing pelvic examination. The doctor will put a speculum in the vagina to examine the cervix. The colposcopy is an instrument mounted with a magnifying glass to let the doctor see clearly the surface of the cervix. The doctor will usually put some liquid of the cervix to show the abnormal area of the cervix, then take a biopsy. The procedure takes around 15-30 minutes.
• Cervical biopsy:  
  • If a tumor is found at the cervix, a tissue sample will be taken and sent for pathology.
• Magnetic resonance imaging (MRI) Pelvis and computed tomography (CT) scan:
  • To determine the area affected by cancer and check for any spread to other organs.
  • MRI is better than CT scan in looking at the soft tissue parts of the pelvis to guide on the subsequent local treatment plan.

Figure: Pelvic MRI showing local invasion of the cervical cancer

There are typically 2 types of cervical cancer:

• Squamous cell carcinomas
  • Cancer cells derived from outer surface of cervix (named squamous cells)
  • Significantly more common (90%)
• Adenocarcinomas
  • Cancer cells derived from glands on inner surface of cervix
  • Less common (around 10%)

In some cases, cervical cancers have features of both types, and are called adenosquamous carcinomas or mixed carcinomas.

Cervical cancer can be classified into 4 stages:

Types of treatments

Cervical cancer is often treatable. The treatment depends on:

• Size and type of cancer
• Site of the cancer and extent of spread
• Your general health

1. Surgery

• Surgery is often the main treatment for early cervical cancer.
• Surgery should be performed by an obstetrician-gynecologist specializing in oncology.  It can be open surgery or laparoscopic or robotic-assisted.
• There are different types of surgeries for cervical cancer:
  1. Conization/ Loop electrosurgical excision (LEEP): Just for removal of cervical cancer that can only be seen with a microscope, called microinvasive cancer
  2. Radical trachelectomy: Mainly for young patients who want to preserve fertility. This procedure involves removal of the whole cervix but keeping the uterus intact.
  3. Hysterectomy, bilateral salpingo-oophorectomy: This procedure removes the uterus, cervix, upper vagina, both fallopian tubes and ovaries. Extensive lymph node dissection is also performed.
• Possible complications:
  • Bleeding or hematocele (collection of blood) of vagina
  • Wound infection
  • Difficulty in urination, usually recover after a period of time
  • Edema (fluid retention causing swelling of the affected area) of lower limbs, mild numbness of the thighs
  • Lymph accumulation in the pelvic cavity causing lymphocele (a large, cystic mass filled with lymphatic fluid) and subsequently get infection
  • Unable to be pregnant
  • (Rare) Damage of the bladder, ureter and rectum during operation
  • (Rare) Damage of the major blood vessels during operation, causing severe bleeding or even death

2. Radiotherapy

• Radiotherapy uses high-energy x-rays to destroy cancer cells. Radiotherapy can be given after surgery to reduce recurrence or given alone to kill the tumor.
• The details and frequency of radiotherapy mainly depend on the pathological type of the cancer, the stage of the cancer, the age and health of the patient.
• Clinical applications of radiation therapy for cervical cancer include:
  • Main treatment, with or without concurrent chemotherapy (usually for Stage IB to 4A cervical cancer) 
  • Adjuvant radiotherapy after surgical resection (to reduce the chance of local recurrence)
• Radiotherapy for cervical cancer can be divided into:
  1. External beam radiotherapy
  2. Brachytherapy (internal radiotherapy)
• If radiotherapy is the main treatment for killing the cancer, you will usually receive 4-5 weeks of external beam radiotherapy then 3-4 times of brachytherapy afterwards.

A. External beam radiotherapy

External beam radiotherapy is the use of linear accelerator to send high-energy rays to the tumor and whole pelvis to eradicate the tumor. 

Procedure:

• You will have a CT for radiotherapy planning.
• Before the CT scan, you will need to drink a few cups of water so that you have a full bladder. The radiation therapist will put a little marker outside the vagina to help assessing the radiation field.
• After the planning CT, your oncologist will decide the final details of your radiotherapy plan.
• A common course of treatment is Monday to Friday, with one treatment per day, for a total duration of about 4 to 7 weeks.
• When radiotherapy is used as the main treatment for cervical cancer, it is usually combined with chemotherapy, called cisplatin. The chemotherapy is given weekly to increase the effectiveness of radiotherapy.
• During treatment, you will be asked to drink a certain amount of water so that your bladder is full (similar to the procedure before planning CT). You will also lie in the same position on the couch as when you had your planning CT. 
• The whole radiotherapy will last for 10 to 20 minutes.

Possible side effects of external beam radiotherapy

Short-term side effects:

• Fatigue
• Sore and red skin in the treatment area
• Bladder irritation and pain
• Stomach discomfort
• Diarrhea or loose stool
• Nausea and vomiting

Long-term side effects:

• Skin over the treatment area becomes tighter and less elastic
• Vaginal dryness and getting narrower
• Swelling of the legs
• Easy fullness of the bladder
• Rarely cause bowel obstruction

B. Brachytherapy (internal radiotherapy)

Brachytherapy or internal radiotherapy means putting a source of radiation in or near the cancer. This treatment gives a high dose of radiation to the cervix but a much lower dose to the surrounding organs.

Procedure

• The entire treatment is conducted in the operating room under general anesthesia or spinal anesthesia. 
• The doctor will put the applications into the vagina and cervix. The applicators are made of a small metal tube, and two small round ovoids or two half-rings. Needles may also be inserted if the tumor is very bulky.
• After the applicators are in place, a CT or MRI will be performed to locate the tumor. The treatment team will produce the brachytherapy plan. 
• Once the plan is ready, the radiation therapist will connect the applicators with the afterloading machine. 
• After treatment, the applicators will be removed.
• Patient usually needs to undergo 3 to 4 times of treatment in 2-3 weeks. The whole process including brachytherapy planning lasts around 2 to 3 hours while the brachytherapy treatment itself lasts for 15 to 25 minutes.

Side effects of brachytherapy:

• Risks from anesthesia
• Urinary tract infection
• Vaginal bleeding
• Fatigue
• Diarrhea
• Bladder irritation or pain
• Narrowing and dryness of the vagina
• Less common: perforation of the uterus, vaginal bleeding

3. Chemotherapy

Anticancer drugs to destroy and disrupt the growth and division of cancer cells, which can shrink the tumor. Chemotherapy is usually given together with radiotherapy as the main stream of treatment in patients with Stage IB to 4A cervical cancer.

Procedure:

• The most common chemotherapy for cervical cancer is cisplatin. If your renal function is not satisfactory, your doctor may switch the regimen to carboplatin or epirubicin.
• You will have chemotherapy once a week over the 4-5 weeks of external beam radiotherapy.
• You will have blood tests before chemotherapy to make sure your cell counts are fit.
• The chemotherapy will be given through a drip (infusion) into one of your veins.

Possible side effects:

• Loss of appetite
• Nausea / vomiting
• Diarrhea
• Fatigue
• Mouth sores
• Increased risk of infection
• Renal impairment
• Neuropathy: numbness of hands and feet

If the cancer has spread to other parts of the body, it is called metastatic disease. Systemic treatment using chemotherapy, targeted therapy or immunotherapy may be used for controlling the disease. Palliative radiotherapy may also be given to control the local symptoms, e.g. bleeding from the tumor or pelvic pain.

1. Chemotherapy

• Chemotherapies for cervical cancer are typically given through a vein. 
• Chemotherapy is usually given in cycles, often given weekly or every 3 weeks.
• Common regimens for metastatic cervical cancer include:
  • Cisplatin
  • Carboplatin
  • Paclitaxel-carboplatin
  • Docetaxel (Taxotere)
  • Irinotecan
  • Topotecan
  • Vinorelbine
• Side effects of chemotherapy:
  • Loss of appetite
  • Nausea / vomiting
  • Diarrhea
  • Fatigue
  • Mouth sores
  • Increased risk of infection
  • Renal impairment
  • Neuropathy: numbness of hands and feet

2. Targeted therapy

• Targeted therapy is a type of drug therapy that stops cancer cells from growing by interfering the specific molecules that help cancer cells to grow or spread. Since the mechanism of action of targeted agent is different from that of chemotherapy, they have different side effects than chemotherapy.
• The most commonly used targeted therapy for advanced cervical cancer is Bevacizumab.
  • Bevacizumab is a monoclonal antibody that targets a cancer cell protein called vascular endothelial growth factor (VEGF). This protein facilitates the growth of new blood vessels so that the tumors can get nutrition to survive. Bevacizumab targets VGFR and stops the cancer from growing blood vessels (anti-angiogensis). 
  • Bevacizumab is often given with platinum-based chemotherapy. It is injected into the veins every 2 to 3 weeks.
• Side effects of Bevacizumab:
  • Fatigue and weakness 
  • High blood pressure
  • Protein in urine
  • Wound healing
  • Easy bleeding or bruising
  • Constipation
  • Blood clots (thrombotic risk)

3. Immunotherapy

• Immunotherapy is an emerging treatment option for patients with advanced cervical cancer. 
• Immune-checkpoint inhibitor, Pembrolizumab, is a monoclonal antibody that helps to restore the body’s immune system to fight the cancer. Pembrolizumab targets and blocks PD-1, a specific protein on the surface of immune cells (T-cells). Blocking PD-1 triggers the T-cells to identify the cancer cells and initiate an attack to kill the cancer cell.
• Pembrolizumab can be used as 
  • first-line treatment together with chemotherapy +/- bevacizumab, or 
  • late-line treatment after failure of chemotherapy
• This immunotherapy drug is given as an intravenous (IV) infusion every 3 or 6 weeks.
• Common side effects:
  • Fatigue and weakness
  • Nausea
  • Skin changes
  • Loss of appetite
  • Hypothyroidism
  • Diarrhea
  • Fever
  • Adrenal insufficiency
• Severe side effects (Incidence is usually low, <5%)
  • Impaired renal function
  • Impaired liver function
  • Severe skin reaction
  • Severe diarrhea
  • Neuropathy
  • Inflammation of the lung 
  • Inflammation of the eyes

4. Radiotherapy

• Radiotherapy can be given to control your symptoms, e.g. bleeding from the cervical cancer, pelvic pain or bone pain.
• External beam radiotherapy is used while brachytherapy is seldom given.
• The treatment is usually short course, rarely more than 10 times.
• Side effects might start a week after radiotherapy but improve around 2 weeks after completion of radiotherapy.
• Side effects include:
  • Tiredness and weakness
  • Reddening or darkening of the skin
  • Nausea
  • Diarrhea

The following ways can help prevent cervical cancer:

• Quit smoking
• Healthy diet. Obesity causes an increase in secretion of female sex hormones, stimulating the thickening of uterine lining.
• Regular exercises. It is suggested to have 30 minutes of aerobic exercise per day.
• Beware of personal hygiene. Practice safer sex. Consistent use of condom can help reduce the chance of HPV infection or other sexually transmitted diseases
• Regular cervical cancer screening (also known as “Pap test”) can reduce the chance of cervical cancer by 90%. Screening should be done once every year at the beginning and after two consecutive normal results, once every three years thereafter. You can refer to the Cervical Screening Programme by the Department of Health (https://www.cervicalscreening.gov.hk/en/index.html).
• Cervical cancer vaccination (HPV vaccine): can learn more at the Centre for Health Protection website (https://www.chp.gov.hk/en/features/102146.html)

What is HPV?

• Human papillomavirus (HPV) is the name of a group of viruses that includes more than 150 genotypes
• Around 40 of these viruses infect the genital area of men and women.
• HPV can cause premalignant changes and malignant cancers of cervix, vagina, vulva and anus.

What is HPV vaccine?

• HPV vaccine is a prophylactic vaccine to prevent cervical cancer as well as other HPV-related cancers or diseases.
• In Hong Kong, HPV-16, 18, 31, 33, 45, 52, 58 accounted for about 90% of cases of cervical cancer. All the above seven genotypes are included in the 9-valent HPV vaccine.
• Vaccination can prevent infection of HPV, but it cannot cure previous infection of HPV. 
• Vaccination cannot replace cervical cancer screening.

What are the types of HPV vaccine available?

Smart Patient Website - Cervical Cancer (ha.org.hk)

Centre for Health Protection - Cervical Cancer (chp.gov.hk)

Cervical Cancer (elderly.gov.hk)

Women-Cancer-booklet-1s.pdf (cancer-fund.org) (Chinese version only)

CervicalCancer.pdf (hkacs.org.hk) (Chinese version only)

Special thanks to Ms. He Yixuan (Class M27), Ms Fung Mong Chi (Class M27), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Wendy Wing-Lok Chan, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article. 

Last updated on 18th Dec, 2023.