Vulvar and Cervical Cancer 4

Question 1

Differentiate between LSIL and HSIL.

Answer 1

• Low Grade (LSIL)
  
  • Types
    
    • Mild dysplasia (CIN 1)
    • Condyloma
  • Productive infection
  • Transient lesions
  • May be clinically undetected
  • Often Low Risk HPV
  • Surveillance vs Laser/Cryo- Ablation
• High Grade (HSIL)
  
  • Types
    
    • Severe dysplasia (CIN 3)
  • Loss of coordination btwn viral gene expression and epithelial differentiation
  • Persistent
  • Premalignant
  • HR HPV
  • Excisional Procedure/Hysterectomy

Question 2

What are the indications for conization (LEEP procedure)? What doess the procedure involve?

Answer 2

• HGSIL Primary Option (vs Colpo Bx)
• Persistent CIN 1 (2yrs)
• CIN 1 preceded by ASC-H/HGSIL
  
  • VS: co-test @12 & 24 mon or path review
• CIN 2 or 3 on Cx Biopsies/ECC
  
  • vs Hysterectomy if re-LEEP not possible
  • Co-Testing 4-6 months
• Pos Margin (CIN 2/3)/ECC on LEEP
• Pos Margin AIS on Cx Bx/LEEP/ECC
  
  • If conservative management planned
• Microinvasive SCCA
  
  • Consider for Hysterectomy Planning

Question 3

What are the symptoms of cervical cancer?

Answer 3

• Most common presentation of invasive cancer:
  
  • abnormal vaginal beeding
  • post-coital bleeding
  • vaginal discharge
• Advanced disease symptoms
  
  • pelvic pain
  • difficulty urinating/defecating
  • metastatic: back pain, leg swelling (unnilateral)
• PE: abnormal lesion on cervix, necrotic/friable
  
  • staging is clinical, including RVE
  • biopsy confirmation

Question 4

Describe the staging of cervical cancer. (Need to know!)

Answer 4

• IA1: <3x7mm
• IA2: >3, <5x7mm
• IB1: clinically visible, = 4cm
• IB2: Clinically visible >4cm
• IIA: Without parametrial involvement,
• IIA1: clinically visible, = 4cm
• IIA2: Clinically visible >4cm
• IIB: with parametrial involvement
• IIIA: lower third of vagina
• IIIB: Pelivc sidewall/hydronephrosis
• IVA: Adjeacent organs
• IVB: Distant mets

Question 5

What is the treatment of the following stages of cervical cancer? IA1, IA2, IB1, IB2-IVA, IVB? When is chemo/XRT an option?

Answer 5

• IA1: CKC, Simple Hysterectomy (Neg LVSI)
• IA2: Modified Radical Hysterectomy + PLND ± PALND
• IB1: Radical Hysterectomy + PLND ± PALND (if lesion
• IB2: IVA Chemo/XRT
• IVB: Chemo +/- palliative XRT
• Chemo/XRT option for patients who are not candidates for hysterectomy

Question 6

What are the main methods of radiation treatment of cervical cancer? What are the advantages of concurrent chemotherapy?

Answer 6

• Radiation:
  
  • Hgb goal >10, optimizes oxygen delivery to tumor, maximize free radical damage to tumor
  • External Beam (teletherapy)
    
    • Whole Pelvis (parametria, pelvic and common iliac lymph nodes)
    • ± Para-aortic window
  • Implant (brachytherapy) 1-2 implant Q2 weeks 1-3 weeks after External Beam
    
    • Central disease (Cervix, medial parametria, vagina)
  • Doses:
    
    • Cumulative: Point A 85 Gy, Point B 55 Gy
• Concurrent Chemo/Radiation:
  
  • Increases Sensitivity Tumor to Radiation: inhibits repair of sub-lethal damage, synchronizes cells to a particularly radiosensitive phase of cell cycle
  • Eradicates microscopic disease
  • Multiple RCT (5) show Chemo/RT better vs XRT alone
  • Chemo:
    
    • Weekly Cisplatin 40mg/m2 most common

Question 7

What makes a screening exam for cervical cancer “good”?

Answer 7

• The disease in question should:
  
  • constitute a significant public health problem, meaning that it is a common condition with significant morbidity and mortality.
    
    • third most common CA in the world with >500K new diagnoses
  • have a readily available treatment with a potential for cure that increases with early detection.
    
    • Untreated CIN3 30yr risk of progression to invasive CA 30%; treated CIN3 30yr risk of progression <1%
• **The test for the disease must: **
  
  • be capable of detecting a high proportion of disease in its preclinical state.
    
    • dysplastic lesions can be detected for 5-10 years prior to progression
  • be safe to administer.
    
    • pelvic examination and pathologist interpretation
  • be reasonable in cost.
  • lead to demonstrated improved health outcomes.
    
    • pap smear has sensitivity of > 95% for detecting squamous lesions >/= CIN2
  • be widely available, as must the interventions that follow a positive result

Question 8

What are the major HPV vaccinations? What is the recommended dosing?

Answer 8

• Recombinant Non-infectious Viral Like Particle
  
  • Capsid alone (L1)
  • Generates an Neutralizing Antibody response
    
    • More robust in children/adolescents 9-15 y/o both sexes vs adults
  • 3 doses over 6 months
    
    • Guardasil: 0, 2, 6 mos
    • Cervarix: 0, 1, 6 mos
  • Prior exposure to one subtype does not prevent vaccine efficiency against remaining subtypes
  • Most common adverse reaction: injection site reactions
• Dosing:
  
  • CDC: 11-12 y/o girls, 13-26 y/o if never vaccinated
  • FDA: 9-26 y/o (9-25 y/o Cervarixâ)
    
    • Not recommended in Pregnancy (limited data)

Question 9

Describe the efficacy of Guardasil and Cervarix.

Answer 9

• Guardasil (Merck):
  
  • Quadrivalent Vaccine (HPV 16, 18, 6, 11)
  • Prevents genital warts in males and females
  • Licenced for males 9-26 y/o
  • Decreases CIN or AIS (assoc 16, 18): >93% prevention efficiency
  • Genital warts: 99% (F), ~90% (M) prevention efficiency
• Cervarix (GlaxoSmithKline):
  
  • Bivalent Vaccine (HPV 16, 18)
  • >93% effective ³CIN 2/3 or AIS (assoc 16, 18) in HPV naïve population