Female Reproductive

• Epithelium of FGT

  Stratified Squamous Mucosa - ectocervix

  • Keratinised - outside
  • Labor majora
  • Labor minora
  • Clitoris
  • Vestibule
  • Clitoris also has erectile tissue and irregular endothelial lined sinuses
  • Non keratinised - inside vagina

  Simple columnar epithelium - endocervix
• Epithelium of the Vagina:

  • stratified squamous epithelium
  • Lamina Propria: thin layer of connective tissue under stratified squamous -> together is the mucosa
• Epithelium of the Cervix

  • Ectocervix
  • Stratified squamous
  • Underlying fibrovascular connective tissue of lamina propia
  • Smooth muscle bundles and lymphocytes
  • Endocervix
  • Simple columnar to secrete mucous
• Epithelium of the Uterus

  • Body of Uterus
  • Simple columnar
  • Endometrium (mucosal layer)
  • Columnar cells (some ciliated - not prominent)
  • Highly reactive to hormonal changes
  • Simple tubular uterine glands extend through entire thickness of lamina propria and are prominent
  • Stroma - small fibroblastic cells with lymphocytes, macrophages and blood vessels
  • Only mucosa takes part in menstrual cycle
  • Myometrium
  • Deep to endometrium
  • Middle layer of uterine wall
  • Contains:
  • Smooth muscle bundles
  • Supporting stroma
  • Vascular tissue
  • Functions:
  • Uterine contractions
• Cervical Intraepithelial Neoplasia (CIN) is a pre-cancerous condition
• Fallopian Tubes

  1. Mucosal Layer
  2. Simple columnar
  3. Muscularis Layer
  4. Smooth muscle
  5. Serosal Layer
  6. Mesothelium
• Ovaries

  • surface epithelium = simple cuboidal
  • Follicular cells = flat epithelial cells of ovary surface
  • Granulosa cells surround follicular cells -> flat to cuboidal and proliferated to produce stratified epithelium
  • Ova -> primordial germ cells
  • ovarian Cortex -> Ovarian follicles and stroma
  • Ovarian Medulla -> centre with no follicles
• Female Reproductive Cancers

  • uterine
  • cervical
  • ovarian and fallopian tubes
  • vaginal
  • vulval carcinoma
• Cervical Cancers:

  1. Squamous cell carcinoma = 65.1%
  2. Adenocarcinoma = 25.7%
  3. Adenosquamous = 3.3%
  4. Other = 5.9%

  Other contributing factors:

  • HIV more aggressive and advanced -> poor prognosis
  • SCC with over expression of C-myc oncogene -> poorer prognosis
  • number of cells in S phase may be prognostic significant in early Cx cancer
  • HPV 18 is an independent adverse molecular prognostic factor
• Pathogenesis of Cervical Cancer

  • most HPV is transient and self-limiting
  • High Risk -> 16/18/31/45 -> account for 90%
  • Adenocarcinoma related HPV18
• Integration of HPV in Cervical Cancer

  • transmission -> skin to skin contact & infection of basal cells of stratified squamous epithelium
  • Once inside - HPV DNA replicates & progresses to surface
  • In basal layer -> virus replication non-productive
  • In suprabasal layer -> switches to a rolling circle mode of DNA replication. Amplified DNA as high copy number synthesises capsid proteins and causes viral assembly
• Low risk HPV: viral DNA located extra-chromosomally in nucleus

  High risk HPV: DNA is integrated into host cell genome. Disrupts E2 which downregulates the transcription of E6 and E7 -> overexpression

  • E6 -> disrupts cell regulatory cycle and binds to p53 and stops apoptosis
  • E7 -> binds to pRb disrupting E2F1 allowing cell to enter S phase of cycle and bind to cyclin E resulting in DNA synthesis and cell proliferation
  • inactivation of p53 and pRb proteins produce increased proliferation rate and genetic instability -> host cell has increased damage DNA that cannot be repaired.
• Cervical Cancer Risk Factors

  • persistent HPV infection
  • HPV variants
  • Genetic predisposition
  • LSIL (CIN1) and HSIL (CIN2/3)
  • number of sexual partners