Cervical Cancer

Overview

Cervical cancer ranks as the fourth most common cancer affecting women worldwide, with approximately 570,000 new cases diagnosed annually. However, in countries with effective screening programs, the incidence has decreased dramatically over the past several decades. The cervix is the cylindrical neck of tissue that connects the uterus to the vagina, and cancer typically develops in the transformation zone where the inner and outer cervical cells meet.

The vast majority of cervical cancers (about 99%) are caused by persistent infection with high-risk types of human papillomavirus (HPV), particularly types 16 and 18. HPV is a common sexually transmitted infection that most sexually active individuals will encounter at some point. While most HPV infections clear naturally within two years, persistent infections with high-risk types can lead to precancerous changes and eventually invasive cancer if left untreated.

Cervical cancer develops slowly, typically progressing through several stages of precancerous changes over 10-20 years before becoming invasive. This slow progression makes it highly preventable through regular screening with Pap tests and HPV testing. The introduction of HPV vaccines has further reduced the risk, particularly when administered before exposure to the virus. There are two main types of cervical cancer: squamous cell carcinoma (about 80-85% of cases) and adenocarcinoma (about 10-15% of cases).

Symptoms

Early-stage cervical cancer often produces no symptoms, which is why regular screening is crucial for detection. As the cancer progresses, symptoms may develop, though these can also be caused by other, less serious conditions. It's important to note that having these symptoms doesn't necessarily mean you have cervical cancer.

Gynecologic Symptoms

• Vaginal discharge - unusual discharge that may be watery, bloody, or have a foul odor
• Pelvic pain - persistent pain in the pelvis or lower abdomen
• Heavy menstrual flow - heavier or longer periods than usual
• Vaginal itching - persistent itching in the vaginal area
• Vulvar irritation - discomfort or irritation of the external genital area

Bleeding Symptoms

• Abnormal vaginal bleeding between periods
• Bleeding after sexual intercourse
• Bleeding after douching
• Bleeding after a pelvic exam
• Post-menopausal bleeding
• Spotting or bleeding that occurs irregularly

Advanced Stage Symptoms

• Jaundice - yellowing of skin and eyes due to liver involvement
• Back pain, particularly in the lower back
• Leg swelling due to lymph node involvement
• Difficulty urinating or blood in urine
• Pain during urination
• Rectal bleeding or pain during bowel movements

Constitutional Symptoms

• Unexplained weight loss
• Fatigue and weakness
• Loss of appetite
• General feeling of being unwell
• Fever (in advanced cases)

When Symptoms Typically Appear

• Precancerous stage: Usually no symptoms
• Early invasive cancer: Abnormal bleeding, discharge
• Advanced cancer: Pelvic pain, constitutional symptoms
• Metastatic disease: Symptoms related to affected organs

Causes

The primary cause of cervical cancer is persistent infection with high-risk types of human papillomavirus (HPV). Understanding the relationship between HPV and cervical cancer has revolutionized prevention and treatment approaches for this disease.

Human Papillomavirus (HPV) Infection

• High-risk HPV types: Types 16, 18, 31, 33, 45, 52, and 58 are most associated with cancer
• HPV 16 and 18: Responsible for about 70% of all cervical cancers
• Persistent infection: Cancer develops only when high-risk HPV persists for years
• Integration into DNA: HPV DNA integrates into cervical cell DNA, disrupting normal cell function
• Oncoproteins E6 and E7: HPV proteins that inactivate tumor suppressor genes p53 and Rb

Progression from HPV to Cancer

• Initial infection: HPV infects cells in the cervical transformation zone
• Persistent infection: Failure of immune system to clear the virus
• Precancerous changes: Low-grade then high-grade squamous intraepithelial lesions
• Invasive cancer: Progression through basement membrane after 10-20 years
• Metastasis: Spread to nearby tissues and distant organs

Cofactors that Increase Risk

• Immune suppression: HIV infection, immunosuppressive medications
• Smoking: Tobacco chemicals concentrate in cervical mucus
• Multiple pregnancies: Hormonal changes and physical stress on cervix
• Long-term oral contraceptive use: Hormonal influence on HPV persistence
• Chlamydia infection: Co-infection may increase cancer risk

Other Rare Causes

• DES exposure: In utero exposure to diethylstilbestrol (clear cell adenocarcinoma)
• Genetic factors: Rare hereditary syndromes affecting DNA repair
• Radiation exposure: Previous radiation therapy to pelvis
• Adenocarcinoma in situ: Precursor to invasive adenocarcinoma

Risk Factors

While HPV infection is the primary cause of cervical cancer, several factors can increase the risk of developing persistent HPV infections and progression to cancer. Understanding these risk factors helps identify women who may benefit from more frequent screening.

Sexual and Reproductive Risk Factors

• Early sexual activity: First intercourse before age 18
• Multiple sexual partners: Increased exposure to HPV
• Partner's sexual history: Partner with multiple previous partners
• Multiple pregnancies: Three or more full-term pregnancies
• Young age at first pregnancy: Before age 20
• History of STIs: Previous sexually transmitted infections

Immune System Factors

• HIV infection: Significantly increases risk of persistent HPV
• Immunosuppressive medications: Organ transplant recipients
• Autoimmune conditions: Conditions requiring immunosuppressive treatment
• Malnutrition: Poor nutritional status affecting immune function
• Chronic stress: May affect immune system function

Lifestyle and Environmental Factors

• Smoking: Doubles the risk of cervical cancer
  • Tobacco by-products found in cervical mucus
  • Damages cervical cell DNA
  • Reduces immune function in cervix
• Long-term oral contraceptive use: Use for 5+ years
• Socioeconomic factors: Limited access to screening and healthcare
• Diet: Low intake of fruits and vegetables

Genetic and Family History Factors

• Family history: Sister or mother with cervical cancer
• HLA type: Certain human leukocyte antigen types
• Genetic variations: Polymorphisms affecting HPV clearance
• DES exposure: Mother took DES during pregnancy

Age and Demographic Factors

• Age: Most common between ages 35-44
• Race/ethnicity: Higher rates in Hispanic, African American, and Native American women
• Geographic location: Higher rates in developing countries
• Lack of screening: Never had Pap test or irregular screening

Diagnosis

Cervical cancer diagnosis involves a systematic approach starting with screening tests and progressing to more definitive diagnostic procedures when abnormalities are detected. Early detection through screening is key to successful treatment outcomes.

Screening Tests

Pap Test (Papanicolaou Test)

• Collects cells from the cervix for microscopic examination
• Can detect precancerous changes and early cancer
• Recommended every 3 years for women ages 21-65
• High sensitivity for detecting abnormal cells

HPV Testing

• Detects presence of high-risk HPV types
• Can be done alone or with Pap test (co-testing)
• Recommended every 5 years for women ages 30-65
• Primary HPV testing now preferred in many guidelines

Diagnostic Procedures

Colposcopy

• Examination of cervix with magnifying instrument
• Performed when Pap test or HPV test is abnormal
• Allows visualization of abnormal areas
• Guides biopsy of suspicious areas

Cervical Biopsy

• Punch biopsy: Small sample of tissue removed
• Endocervical curettage: Sampling from inside cervical canal
• Cone biopsy (conization): Larger, cone-shaped sample removed
• LEEP procedure: Loop electrosurgical excision procedure

Staging and Imaging Studies

Clinical Staging

• Stage I: Confined to cervix
• Stage II: Extends beyond cervix but not to pelvic wall
• Stage III: Lower third of vagina or pelvic wall involvement
• Stage IV: Spread to nearby organs or distant metastases

Imaging Studies

• MRI: Best for assessing local tumor extent
• CT scan: Evaluates lymph nodes and distant metastases
• PET/CT: Combines metabolic and anatomic imaging
• Chest X-ray: Screens for lung metastases

Laboratory Tests

• Complete blood count (CBC)
• Comprehensive metabolic panel
• Liver function tests
• Kidney function tests
• Urinalysis

Treatment Options

Treatment for cervical cancer depends on the stage of the disease, the patient's age and overall health, and personal preferences. Early-stage cancers have excellent cure rates with appropriate treatment, while advanced cancers require multimodal therapy approaches.

Surgery

Early-Stage Disease (Stage I-IIA)

• Conization: Removal of cone-shaped piece of cervix
  • May be curative for very early cancers
  • Preserves fertility
  • Requires close follow-up
• Simple hysterectomy: Removal of uterus and cervix
  • For stage IA1 disease
  • Can be done laparoscopically or robotically
  • Shorter recovery time
• Radical hysterectomy: Extensive removal including surrounding tissues
  • Standard treatment for stage IB-IIA
  • Includes removal of parametria and upper vagina
  • Usually includes pelvic lymph node dissection

Fertility-Sparing Surgery

• Radical trachelectomy: Removes cervix while preserving uterus
• Appropriate for young women with early-stage disease
• Allows possibility of future pregnancy
• Requires careful patient selection

Radiation Therapy

External Beam Radiation

• High-energy beams directed at tumor from outside body
• Usually given 5 days per week for 5-6 weeks
• Often combined with chemotherapy
• May cause fatigue and skin irritation

Brachytherapy

• Radioactive material placed directly in or near tumor
• Delivers high dose to tumor while sparing normal tissue
• Usually follows external beam radiation
• May be high-dose rate (HDR) or low-dose rate (LDR)

Chemotherapy

• Concurrent chemoradiation: Standard for advanced local disease
  • Cisplatin most commonly used
  • Given weekly during radiation
  • Improves survival compared to radiation alone
• Neoadjuvant chemotherapy: Given before surgery or radiation
• Adjuvant chemotherapy: Given after primary treatment
• Palliative chemotherapy: For metastatic or recurrent disease

Targeted Therapy and Immunotherapy

• Bevacizumab: Anti-angiogenesis drug for recurrent disease
• Pembrolizumab: PD-1 inhibitor for recurrent/metastatic disease
• Combination approaches: Combining multiple targeted agents
• Personalized medicine: Treatment based on tumor genetics

Treatment by Stage

• Stage I: Surgery (hysterectomy or trachelectomy)
• Stage II: Chemoradiation or radical surgery
• Stage III: Chemoradiation (primary treatment)
• Stage IV: Palliative chemotherapy, radiation for symptoms
• Recurrent: Individualized based on location and prior treatment

Prevention

Cervical cancer is one of the most preventable cancers through vaccination, screening, and lifestyle modifications. Comprehensive prevention strategies have dramatically reduced cervical cancer rates in countries with effective programs.

HPV Vaccination

• Primary prevention: Most effective way to prevent cervical cancer
• Current vaccines:
  • Gardasil 9: Protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58
  • Prevents 90% of cervical cancers
• Recommended age:
  • Routine vaccination at age 11-12
  • Catch-up vaccination through age 26
  • May be given up to age 45 after discussion with doctor
• Dosing schedule:
  • 2 doses if started before age 15
  • 3 doses if started at age 15 or older

Screening Programs

• Regular Pap tests: Every 3 years for ages 21-65
• HPV testing: Every 5 years for ages 30-65 (primary HPV testing)
• Co-testing: Pap and HPV every 5 years for ages 30-65
• Follow-up: Appropriate management of abnormal results
• Access to care: Ensure all women have access to screening

Lifestyle Modifications

• Safe sexual practices:
  • Limit number of sexual partners
  • Use condoms consistently (reduces but doesn't eliminate HPV risk)
  • Delay sexual activity
  • Choose partners with fewer previous partners
• Smoking cessation: Quit smoking to reduce cancer risk
• Healthy diet: Increase fruits and vegetables consumption
• Weight management: Maintain healthy body weight

Special Populations

• HIV-positive women: More frequent screening (annually)
• Immunosuppressed women: Enhanced screening protocols
• DES-exposed women: Specialized screening and follow-up
• Post-hysterectomy: Continued screening if history of high-grade lesions

Global Prevention Strategies

• WHO elimination strategy: 90% vaccination, 70% screening, 90% treatment
• Single-visit approach in resource-limited settings
• Integration with other reproductive health services
• Education and awareness campaigns

When to See a Doctor

Seek immediate medical attention for:

• Heavy vaginal bleeding that soaks through a pad every hour
• Severe pelvic pain that is sudden or worsening
• Signs of severe anemia: dizziness, fainting, rapid heartbeat
• Fever with pelvic pain
• Inability to urinate or severe pain with urination

Schedule prompt gynecologic evaluation for:

• Abnormal vaginal bleeding between periods
• Bleeding after sexual intercourse
• Post-menopausal bleeding
• Unusual vaginal discharge with odor
• Persistent pelvic pain
• Pain during sexual intercourse

Routine screening and check-ups for:

• Regular Pap tests as recommended by guidelines
• HPV vaccination consultation
• Discussion of abnormal menstrual patterns
• Family history of gynecologic cancers
• History of abnormal Pap tests
• HIV or immunosuppression requiring enhanced screening

Follow-up care for:

• Abnormal Pap test results
• Positive HPV test results
• History of cervical dysplasia
• Completion of cervical cancer treatment

Related Conditions

• Endometrial Cancer
• Ovarian Cancer
• Vulvar Cancer
• Vaginal Cancer
• Human Papillomavirus (HPV)
• Pelvic Inflammatory Disease

Frequently Asked Questions

References

1. Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70(5):321-346.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer. Version 1.2024.
3. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination - updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408.
4. Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169-182.
5. World Health Organization. WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. Geneva: World Health Organization; 2021.