Cervical Intraepithelial neoplasia (CIN)

Risk factors

  • Persistent infection of high risk HPV*
    • 16, 18, 31, 33, 35, 6… (16 & 18 cause 70% of all cervical cancers)
  • Many sexual partners
  • Vulnerability of the squamo-columnar junction in early reproductive life
    • Age of first intercourse
    • Long-term use of the OCP
    • Non-use of barrier protection
  • Smoking
  • Immunosuppression

* See also Genital warts (6 & 11)- in which there is thickening and ‘papillomatous’ epithelium with cytoplasmic vacuolation.  In 16 & 18 (CIN), the infected epithelium remains flat, but may still show vacuolation (koilocytosis), which can be detected in smears.  HPV 16/18 is more common in younger women (15-25 higher than 25-35, higher than 35-45 etc etc).

Timelines

  • HPV Infection -> High-grade CIN (6 months – 3 years)
  • High grade CIN -> Invasive cancer (5-25 years)

Diagnosis

  • Screening (smear) will only show dysmorphic cells and will NOT tell you the grade/stage of CIN.  For this, a biopsy is required:
    • Punch biopsy
    • Cone biopsy (more extensive evaluation)
  • To view the effected area more easily, ‘staining’ of the cervix can be done using acetic acid, which causes the affected (CIN) areas to show up whiter than the surrounding normal tissue.

Pathology

  • Pre-invasive stage of cervical cancer
    • not grossly visible (it does NOT cause symptoms)
    • Detectable by screening
  • Occurs at the SCJ and can involve a large area
    • Dysplasia of squamous cells
      • Delay in maturation/differentiation
        • Immature basal cells occupy more of the epithelium than normal
      • Nuclear abnormalities
        • hyperchromasia
        • increased nuclear:cytoplasm ratio
        • pleomorphism
      • Excess mitotic activity
        • Activity above the basal layer
        • Abnormal mitotic figures
      • Koilocytosis

Grading

  1. CIN1
    1. Basal 1/3 of epithelium occupied by abnormal cells (increased mitotic activity)- but surface cells quite mature (although some nuclear atypia)
  2. CIN2
    1. Basal 2/3 of the epithelium occupied…
  3. CIN3
    1. Full thickness

 Staging (NB not the same)

Management

Management largely depends on the stage, but stage 2/3 is generally managed by loop excision (electrical), to excise the cells.

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