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Cervical Cancer for USMLE Step 1

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Cervical Cancer for the USMLE Step 1 Exam
Definition and Epidemiology
  • Definition
    • Cervical cancer is a malignancy arising from the cervix, most commonly at the transformation zone where squamous and columnar epithelia meet.
    • Primary histologic types include squamous cell carcinoma (80%) and adenocarcinoma (15%).
  • Epidemiology
    • Fourth most common cancer in women globally, with the highest incidence in low- and middle-income countries.
    • The incidence has decreased in developed countries due to HPV vaccination and routine screening.
Risk Factors
  • Human Papillomavirus (HPV) Infection:
    • Persistent infection with high-risk HPV strains (especially types 16 and 18) is the leading cause.
  • Sexual Behavior:
    • Early age at first sexual intercourse and multiple sexual partners increase HPV exposure risk.
  • Smoking:
    • Increases cervical cancer risk, likely due to immunosuppressive and carcinogenic effects on cervical cells.
  • Immunosuppression:
    • Conditions like HIV/AIDS and immunosuppressive drugs increase susceptibility to persistent HPV infection and cancer progression.
  • Long-Term Oral Contraceptive Use:
    • Extended use of oral contraceptives is associated with a slightly elevated risk, which decreases after discontinuation.
Pathophysiology
  • HPV-Driven Oncogenesis:
    • High-risk HPV strains produce E6 and E7 oncoproteins, which inactivate tumor suppressor proteins p53 and Rb, promoting uncontrolled cell growth.
  • Cervical Intraepithelial Neoplasia (CIN):
    • CIN is classified 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 CIN 3 have a higher risk of progressing to invasive cancer.
Clinical Manifestations
  • Early Disease:
    • Often asymptomatic; abnormal findings may be identified on routine Pap smear screening.
  • Advanced Disease:
    • Common symptoms include abnormal vaginal bleeding (postcoital, intermenstrual, or postmenopausal), pelvic pain, and increased vaginal discharge.
    • Severe cases may cause urinary or bowel symptoms if the cancer invades adjacent organs.
Diagnosis
  • Screening:
    • Pap Smear (Cytology): Identifies cervical dysplasia and is 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: Helps detect high-risk HPV strains, often used in combination with Pap smear for higher sensitivity.
Cervical Cancer Cells
  • Colposcopy:
    • Used for further evaluation of abnormal Pap smear results, allowing visual examination and biopsy of abnormal cervical tissue.
  • Biopsy:
    • Confirms diagnosis and determines the grade of CIN or presence of invasive cancer.
  • Imaging:
    • MRI and CT scans may be used to assess the spread in advanced cases.
Staging
  • FIGO Staging:
    • Stage I: Cancer confined to the cervix.
    • Stage II: Cancer extends beyond the cervix but not to the pelvic wall.
    • Stage III: Involves pelvic wall or lower third of the vagina.
    • Stage IV: Spread to adjacent organs or distant sites (e.g., bladder, rectum, lungs).
Treatment
  • Early-Stage Disease (Stage IA1-IB1):
    • Conization or Simple Hysterectomy: Suitable for microinvasive disease and for patients seeking fertility preservation.
    • Radical Hysterectomy with Pelvic Lymphadenectomy: Preferred for more invasive early-stage cancer without spread to the parametrium.
  • Locally Advanced Disease (Stage IB2-IVA):
    • Radiation Therapy with Concurrent Chemotherapy: Standard treatment to control local and regional spread, typically using cisplatin-based chemotherapy.
  • Metastatic Disease (Stage IVB):
    • Systemic Chemotherapy: Palliative approach involving cisplatin, paclitaxel, and sometimes bevacizumab for advanced cases.
Prevention
  • HPV Vaccination:
    • Recommended for girls and boys aged 11-12, with catch-up vaccination up to age 26.
    • The vaccine covers multiple high-risk HPV types, including types 16 and 18, effectively reducing cervical cancer incidence.
  • Screening:
    • Routine Pap smear and HPV testing significantly reduce cervical cancer incidence and mortality.
    • Screening typically begins at age 21 and includes co-testing from age 30 to 65.
Key Points
  • Cervical Cancer is primarily caused by persistent infection with high-risk HPV types, particularly HPV 16 and 18.
  • Risk Factors: HPV infection, smoking, immunosuppression, and prolonged oral contraceptive use.
  • Screening and Prevention:
    • Regular Pap smear and HPV testing help reduce incidence; vaccination prevents infection with high-risk HPV strains.
  • Symptoms: Early disease is asymptomatic, while advanced disease may present with abnormal vaginal bleeding, pelvic pain, or urinary symptoms.
  • Diagnosis: Relies on Pap smears, colposcopy with biopsy, and imaging for staging.
  • Treatment:
    • Early stages may be managed surgically.
    • Locally advanced disease typically requires chemoradiation.
  • Prevention: HPV vaccination and routine screening remain the most effective strategies for reducing cervical cancer incidence and mortality.

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