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Cervical Cancer for USMLE Step 3

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Cervical Cancer for the USMLE Step 3 Exam
Definition and Epidemiology
  • Definition
    • Cervical cancer originates from the cervix, typically in the transformation zone where squamous and columnar epithelium meet.
    • Main histologic types are squamous cell carcinoma (80%) and adenocarcinoma (15%).
  • Epidemiology
    • Globally, cervical cancer is a major cause of morbidity and mortality, particularly in low-resource countries.
    • The incidence is declining in developed countries due to HPV vaccination and routine screening.
Risk Factors
  • Human Papillomavirus (HPV) Infection:
    • Persistent infection with high-risk HPV types (especially 16 and 18) is the primary cause.
  • Early Sexual Activity and Multiple Sexual Partners:
    • Increase the likelihood of HPV exposure and infection.
  • Smoking:
    • Increases risk by immunosuppressive effects and accumulation of carcinogens in cervical mucus.
  • Immunosuppression:
    • Conditions like HIV/AIDS and immunosuppressive medications impair immune response to HPV, increasing the risk of progression to cancer.
  • Prolonged Oral Contraceptive Use:
    • Long-term use slightly elevates the risk, but risk declines after cessation.
Pathophysiology
  • HPV Oncogenesis:
    • High-risk HPV types produce E6 and E7 oncoproteins that inactivate tumor suppressors p53 and Rb, leading to uncontrolled cellular proliferation.
  • Cervical Intraepithelial Neoplasia (CIN):
    • Precancerous lesions are categorized as CIN 1 (mild dysplasia), CIN 2 (moderate dysplasia), and CIN 3 (severe dysplasia or carcinoma in situ).
    • CIN 1 often regresses, while CIN 2 and 3 have a higher risk of progression to invasive carcinoma, particularly in immunocompromised patients.
Clinical Manifestations
  • Early Disease:
    • Asymptomatic and often detected through routine screening (Pap smear).
  • Advanced Disease:
    • Common symptoms include abnormal vaginal bleeding (postcoital, intermenstrual, or postmenopausal), pelvic pain, and increased vaginal discharge.
    • Invasion into adjacent organs may cause urinary or bowel symptoms.
Diagnosis
  • Screening:
    • Pap Smear (Cytology): Recommended every 3 years for women aged 21-29 and every 5 years with HPV co-testing from age 30 to 65.
Cervical Cancer Cells
    • HPV DNA Testing: Detects high-risk HPV strains, often used in combination with cytology for increased sensitivity.
  • Colposcopy:
    • Used to evaluate abnormal Pap results, with magnified visualization of cervical lesions and directed biopsy for diagnosis.
  • Biopsy:
    • Confirms diagnosis and helps assess the degree of dysplasia or invasion.
  • Imaging:
    • MRI and CT evaluate tumor extent in advanced disease; PET-CT may be used to detect distant metastasis.
Staging
  • FIGO Staging:
    • Stage I: Confined to cervix.
    • Stage II: Extends beyond cervix but not to pelvic wall.
    • Stage III: Involves pelvic wall or lower third of the vagina.
    • Stage IV: Spread to adjacent organs or distant metastasis (e.g., bladder, rectum, lungs).
Treatment
  • Early-Stage Disease (Stage IA1-IB1):
    • Conization or Simple Hysterectomy: Used for microinvasive disease in women desiring fertility preservation.
    • Radical Hysterectomy with Pelvic Lymphadenectomy: Indicated for invasive lesions confined to the cervix.
  • Locally Advanced Disease (Stage IB2-IVA):
    • Radiation Therapy with Concurrent Chemotherapy: Standard of care to treat regional and local spread, often using cisplatin-based regimens.
  • Advanced or Metastatic Disease (Stage IVB):
    • Systemic Chemotherapy: Palliative approach with agents such as cisplatin, paclitaxel, and sometimes bevacizumab.
Prevention
  • HPV Vaccination:
    • Recommended for boys and girls aged 11-12, with catch-up vaccination available up to age 26.
    • Covers multiple high-risk HPV types and reduces cervical cancer risk.
  • Screening:
    • Regular Pap smear and HPV testing reduce cervical cancer incidence and mortality.
    • Screening begins at age 21 and involves co-testing from age 30 to 65.
Key Points
  • Cervical Cancer is largely caused by persistent HPV infection, primarily HPV types 16 and 18.
  • Risk Factors include HPV infection, smoking, immunosuppression, and prolonged oral contraceptive use.
  • Screening and Prevention:
    • Routine Pap smears, HPV testing, and vaccination reduce cervical cancer risk.
  • Symptoms: Early disease is often asymptomatic; advanced stages present with abnormal bleeding, pelvic pain, or urinary symptoms.
  • Diagnosis: Pap smear screening, colposcopy with biopsy, and imaging for staging are essential for diagnosis and management.
  • Treatment:
    • Early stages are managed surgically.
    • Locally advanced disease typically requires chemoradiation.
    • Advanced cases are managed with palliative chemotherapy.
  • Prognosis: Favorable for early-stage disease; worsens as cancer progresses to advanced stages.

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