HemeOnc

Cervical Cancer

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Cervical Cancer, Cervix Carcinoma, Cervical Adenocarcinoma In-Situ, Pre-invasive Cervical Cancer, Carcinoma In Situ of Uterine Cervix

  • Epidemiology
  1. Ages Effected
    1. Peak: Ages 40-60 years
      1. Incidence at ages 40-49 years old: 14 per 100,000/year
      2. More than 40% of women are >40 years old at time of diagnosis
    2. Range: 20 to 80 years
  2. Cervical Cancer Incidence
    1. United States: 12,820 cases per year with 4210 deaths (2017, ACS)
    2. World: 500,000 cases per year
      1. Developing countries (without adequate screening) account for 85% of Cervical Cancer cases
    3. Lifetime risk in U.S.: 0.8% if routinely screened
  3. Precursor lesion Incidence (Low Grade SIL)
    1. Low Grade SIL common in young (5-10%)
    2. Progresses to high grade SIL in 3 years (15-20%)
  4. In the U.S., compared with white women
    1. Mortality is increased in hispanic women
    2. Mortality is 2 fold higher in black women
  • History
  1. Cervical Cancer had been as common as Breast Cancer before 1940
  2. Pap Smear markedly decreased U.S. Incidence after 1940
  • Risks
  1. Increased sexual partners
    1. More than one sex partner RR>2 (RR 3 if >5 sex partners)
    2. Prostitute: 4 fold increased risk
  2. Early age of first intercourse under age 18 years (RR >2)
  3. Male Partner with history of multiple partners
  4. Tobacco use confers 1.5-3 fold increased risk (squamous cell Cervical Cancer)
  5. Immunosuppression
    1. HIV Infection
    2. Chemotherapy
    3. Immunosuppressive drugs
  6. Previous abnormal Pap Smear or cervical biopsy
    1. ASCUS most common abnormality before HGSIL or cancer
    2. Kinney (1998) Obstet Gynecol 91:973-6 [PubMed]
  7. Lack of previous Pap Smear (50% of cancer patients)
  8. No Pap Smear in last 5 years (10% of cancer patients)
  9. History of Sexually Transmitted Disease (including HPV)
  10. Long term Oral Contraceptive use >5 years (2 fold increased risk)
  11. Lower socioeconomic class
  12. Uncircumcised male partner
    1. Castellsague (2002) N Engl J Med 346:1105-12 [PubMed]
  13. Vitamin Deficiency (unconfirmed)
    1. Vitamin C Deficiency
    2. B-Carotene deficiency
  • Pathophysiology
  1. Cervical Cancer is a Sexually Transmitted Disease
    1. HPV is found in all but 0.3% of Cervical Cancers
    2. HPV is common (affects 50% of U.S. adults 20-25 years old)
      1. Immune system clears HPV in 6 months for 50% and 2 years for 90% of women
  2. Human Papillomavirus (HPV)
    1. High risk types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68
      1. Types 16 (especially) and 18 account for 70% of Cervical Cancers
      2. Low risk types (6 and 11) cause anogenital warts and are not typically associated with Cervical Cancer
    2. Inactivates gene locus p53
    3. Eliminates malignancy regulation, tumor suppression
    4. Develops cervical intraepithelial neoplasia (CIN 1) which typically regresses
      1. In some cases may progress to CIN2 or CIN3
      2. CIN3 progresses to cervical cncer within 5 years in 20% of untreated cases
  • Types
  1. Squamous Cell Carcinoma (71%)
    1. Keratinizing carcinoma
    2. Non-keratinizing carcinoma
    3. Verrucous carcinoma
  2. Adenocarcinoma (25%)
    1. Clear Cell Carcinoma
    2. Endometrioid carcinoma
  3. Adenosquamous Carcinoma (4%)
    1. Adenoid cystic carcinoma
    2. Small cell carcinoma
    3. Undifferentiated carcinoma
  • Symptoms
  1. Typically asymptomatic
  2. Abnormal Uterine Bleeding or postcoital bleeding
  3. Larger lesions may cause regional symptoms
    1. Bladder outlet obstruction
    2. Back pain or Pelvic Pain
    3. Hematuria
    4. Post-Renal Failure
  • Evaluation
  1. Cervical Cancer Screening
    1. See Pap Smear (Cervical Cytology)
    2. HPV Screening
  2. Cervical Cancer Diagnosis
    1. See Colposcopy
    2. See Colposcopy Findings
    3. Some exophytic or ulcerated lesions may be visible on speculum exam without magnification
    4. Some larger cervical lesions may be palpable on pelvic exam
  • Imaging
  1. CT, PET or MRI Pelvis
    1. May be indicated for staging
  • Staging
  1. Cervical Adenocarcinoma-in-situ (Pre-invasive Cervical Cancer)
    1. Cervical Cancer onset when high grade cervical lesions (CIN2-CIN3) spread beyond basement membrane
  2. Stage I: Cancer confined to Cervix
    1. IA: Microscopic invasion into stroma only (93% five year survival)
      1. IA1: <=3 mm depth, <=7 mm width
      2. IA2: 3-5 mm depth, <=7 mm width
    2. IB: Larger microscopic lesions than IA or any visible cervical lesions (80% five year survival)
      1. IB1: <=4 cm lesion
      2. IB2: >4 cm lesion
  3. Stage II: Cancer spread to vagina (not to distal third) or neighboring tissue (but not to pelvic wall)
    1. IIA: No parametrial invasion (63% five year survival)
      1. IIA1: <=4 cm lesion
      2. IIA2: >4 cm lesion
    2. IIB: Parametrial invasion (58% five year survival)
  4. Stage III: Cancer extension to pelvic wall or distal/lower third of vagina, or Hydronephrosis
    1. IIIA: Involves lower third of vagina, but not pelvic wall (35% five year survival)
    2. IIIB: Involves pelvic wall or causes Hydronephrosis (32% five year survival)
  5. Stage IV: Cancer extension beyond Pelvis, Bladder mucosa or Rectum
    1. IVA: Spread to adjacent pelvic organs (16% five year survival)
    2. IVB: Spread to distant pelvic organs (15% five year survival)
  6. References
    1. (2014) Int J Gynaecol Obstet 125(2): 97-8 [PubMed]
  • Management
  • Initial
  1. Background
    1. Best outcomes are at regional cancer centers
    2. Woo (2012) Cochrane Database Syst Rev (3): CD007945 [PubMed]
  2. Cervical Adenocarcinoma-in-situ (Pre-invasive Cervical Cancer)
    1. Option 1: Hysterectomy (preferred)
    2. Option 2: Conservative management (fertility desired)
      1. Diagnostic Excision margins negative
        1. Long-term close follow-up
      2. Diagnostic Excision margins or ECC positive
        1. Re-excision (preferred) OR
        2. Re-evaluation at 6 months with HPV and cytology co-testing AND Colposcopy with ECC
    3. (2014) ASCCP Guidelines
      1. http://www.asccp.org/Guidelines-2/Management-Guidelines-2
  3. Stage 1
    1. Stage IA1 with microinvasive disease only (no LVSI or Lymphovascular space invasion)
      1. Simple Hysterectomy (or fertility sparing conization if margins negative)
      2. Oophorectomy if cervical adenocarcinoma (higher risk of metastases to ovaries)
    2. Stage IA2 and IB
      1. Radical Hysterectomy with pelvic lymphadenectomy
      2. Pelvic Radiation Therapy with adjuvant platinum-based Chemotherapy
  4. Stage 2
    1. Radical Pelvic Surgery
    2. Pelvic Radiation Therapy with adjuvant platinum-based Chemotherapy
  5. Stage 3
    1. Pelvic Radiation Therapy with adjuvant platinum-based Chemotherapy
  6. Stage 4
    1. Platinum-based Chemotherapy
    2. Pelvic Radiation Therapy
    3. Bevacizumab (Avastin)
  7. Recurrent or persistent disease
    1. Radiation Therapy (if not already done)
    2. Bevacizumab (Avastin)
    3. Radical Hysterectomy (if not already done) OR
    4. Pelvic exenteration (up to 50% cure rate, but 5% mortality)
      1. Removes pelvic organs, lower urinary tract and rectosigmoid colon
  • Management
  • Surveillance
  1. Symptoms of recurrence
    1. Vaginal Discharge
    2. Vaginal Bleeding
    3. Pelvic Pain (including Dyspareunia)
    4. Bone pain (metastases) or other regional symptom depending on site
  2. Initial Surveillance
    1. Gynecologic oncology visits every 3-6 months for the first 2-5 years after treatment
  3. Later Surveillance (after gyn-onc releases patient from their routine follow-up)
    1. Annual exams with primary provider including pelvic exam and vaginal cytology
  4. Focal symptom management
    1. Vaginal lubrication
    2. Pelvic Floor Exercises
    3. Cystitis or Proctitis
  5. Other management
    1. Tobacco Cessation
    2. Major Depression screening
  • Prognosis
  1. Carcinoma-in-situ (Preinvasive): 99% cure rate
  2. See five year survival rates in staging above
  3. Highest risk time for recurrence (including metastases) is in the first 3 years after treatment
  4. Survival is markedly reduced by lymphovascular space invasion (LVSI) even in early stage Cervical Cancers
  5. Prognosis is worse for cervical adenocarcinoma than cervical Squamous Cell Carcinoma
    1. Cervical adenocarcinoma >2 cm has higher risk of lymph node involvement, and higher recurrence rate
  • Prevention