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Cervical Cancer for USMLE Step 2

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Cervical Cancer for the USMLE Step 2 Exam
Definition and Epidemiology
  • Definition
    • Cervical cancer arises from the cervix, most commonly at the squamocolumnar junction (transformation zone) where squamous and columnar cells meet.
    • The primary histologic types are squamous cell carcinoma (80%) and adenocarcinoma (15%).
  • Epidemiology
    • Cervical cancer is a leading cause of cancer death worldwide but has decreased in incidence in developed countries due to screening and HPV vaccination.
Risk Factors
  • Human Papillomavirus (HPV) Infection:
    • Persistent infection with high-risk HPV strains, especially types 16 and 18, is the main cause of cervical cancer.
  • Early Sexual Activity and Multiple Sexual Partners:
    • Increase the risk of HPV exposure and infection.
  • Smoking:
    • Increases cervical cancer risk, possibly due to immunosuppressive and carcinogenic effects on cervical tissue.
  • Immunosuppression:
    • Conditions like HIV/AIDS impair immune response, making persistent HPV infections and progression to cancer more likely.
  • Prolonged Oral Contraceptive Use:
    • Long-term use of oral contraceptives (≥5 years) slightly increases cervical cancer risk.
Pathophysiology
  • HPV Oncogenesis:
    • High-risk HPV strains produce oncoproteins E6 and E7, which inactivate p53 and Rb tumor suppressor proteins, leading to cellular proliferation.
  • Cervical Intraepithelial Neoplasia (CIN):
    • Classified as CIN 1 (mild dysplasia), CIN 2 (moderate dysplasia), and CIN 3 (severe dysplasia or carcinoma in situ).
    • CIN 1 may regress, while CIN 2 and CIN 3 have a higher risk of progressing to invasive carcinoma.
Clinical Manifestations
  • Early Disease:
    • Often asymptomatic and detected by screening tests (Pap smear).
  • Advanced Disease:
    • Symptoms may include abnormal vaginal bleeding (postcoital, intermenstrual, or postmenopausal), pelvic pain, and increased vaginal discharge.
    • In severe cases, invasion into adjacent structures can cause urinary or rectal symptoms.
Diagnosis
  • Screening:
    • Pap Smear (Cytology): Recommended every 3 years for women aged 21-29 and every 5 years with HPV co-testing for women aged 30-65.
    • HPV DNA Testing: Screens for high-risk HPV types and is often combined with cytology.
Cervical Cancer Cells
  • Colposcopy:
    • Conducted for abnormal Pap results, allowing magnified visualization of cervical lesions and targeted biopsy.
  • Biopsy:
    • Histopathologic examination confirms diagnosis and assesses the degree of dysplasia or invasion.
  • Imaging:
    • MRI or CT can assess disease spread in advanced cases; PET-CT is used to detect metastasis and stage advanced disease.
Staging
  • FIGO Staging:
    • Stage I: Confined to cervix.
    • Stage II: Extends beyond cervix, not to the pelvic wall.
    • Stage III: Involves pelvic wall or lower third of vagina.
    • Stage IV: Spread to adjacent organs or distant metastasis.
Treatment
  • Early-Stage Disease (Stage IA1-IB1):
    • Conization or Simple Hysterectomy: Appropriate for microinvasive lesions, especially in fertility-preserving cases.
    • Radical Hysterectomy with Pelvic Lymphadenectomy: Indicated for invasive lesions without parametrium involvement.
  • Locally Advanced Disease (Stage IB2-IVA):
    • Radiation Therapy with Concurrent Chemotherapy: Standard for controlling local disease and treating regional spread, typically with cisplatin-based chemotherapy.
  • Metastatic Disease (Stage IVB):
    • Systemic Chemotherapy: Cisplatin and paclitaxel, sometimes with bevacizumab for palliative treatment.
Prevention
  • HPV Vaccination:
    • Recommended for boys and girls aged 11-12, with catch-up vaccinations for those up to age 26.
    • Covers high-risk HPV types, significantly reducing cervical cancer incidence.
  • Screening:
    • Regular Pap smear and HPV testing reduce incidence, with guidelines recommending screening from ages 21 to 65.
Key Points
  • Cervical Cancer is largely caused by persistent HPV infection, particularly types 16 and 18.
  • Risk Factors include HPV infection, smoking, immunosuppression, and prolonged oral contraceptive use.
  • Screening and Prevention:
    • Routine Pap smear and HPV testing reduce incidence and mortality.
    • HPV vaccination effectively prevents infection with high-risk HPV strains.
  • Symptoms: Early disease is often asymptomatic; advanced disease presents with abnormal vaginal bleeding, pelvic pain, or urinary symptoms.
  • Diagnosis: Relies on Pap smears, colposcopy with biopsy, and imaging for staging.
  • Treatment:
    • Early stages are managed with surgery.
    • Locally advanced disease is treated with chemoradiation.
  • Prognosis is favorable in early-stage disease and worsens with more advanced stages.

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