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