Pathology of the uterine cervix

1. Cervical Anatomy

• Cervix = lower narrow part of uterus joining vagina.
• Acts as barrier against vaginal flora and air entering uterus.
• Two parts:
  • Endocervix — passage between external os + uterine cavity; lined by columnar (glandular) epithelium.
  • Exocervix — projects into vagina; lined by squamous epithelium.
• Squamocolumnar junction (transformation zone) — where the two meet; in exocervix.
  • Exposed columnar epithelium appears reddened and moist.
  • Reserve cells here undergo squamous metaplasia, dysplasia, and carcinoma.
  • This is the site of most cervical cancers.

2. Cervicitis

• Extremely common; mucopurulent to purulent discharge.
• Types:
  • Infectious: Chlamydia trachomatis, N. gonorrhoeae, Trichomonas vaginalis
  • Non-infectious: chemical, mechanical
• Detected on routine exam or via leukorrhea.

3. Endocervical Polyp

• Benign proliferation: fibrovascular core + endocervical glandular/metaplastic squamous epithelium.
• Secondary to chronic inflammation.
• Several cm; soft, cystic spaces with mucinous secretion; lined by mucus-secreting columnar cells.
• Chronic inflammation → squamous metaplasia + ulceration.

4. Tumors of the Cervix — Overview

• Major cause of cancer-related deaths in women worldwide.
• Used to be most frequent cancer in women; Pap smear → dramatic ↓ incidence; most successful screening test for cancer.
• Nearly all invasive cervical SCC arise from CIN (cervical intraepithelial neoplasia) precursor lesion.
• Not all CIN progress to invasive cancer.

5. Cervical Intraepithelial Neoplasia (CIN)

Overview

• Spectrum of HPV-associated squamous lesions.
• Peak incidence: ~30 yr (invasive cancer ~45 yr).

Risk factors

• Early age at first intercourse
• Multiple sexual partners
• HPV-infected partner
• Persistent infection with high-risk HPV
• Smoking + immunodeficiency

Histological grading

Grade	Histology	Bethesda
CIN I	Mild dysplasia; koilocytotic atypia in superficial layers	LSIL
CIN II	Moderate dysplasia; delayed maturation into middle third	HSIL
CIN III	Severe dysplasia / carcinoma in situ; full-thickness atypia, no koilocytosis	HSIL

HPV biology

• High-risk types (16, 18, 31, 45) → HSIL + invasive carcinoma:
  • Viral genome integrates into host genome.
  • E6 protein → inactivates p53.
  • E7 protein → inactivates RB.
  • → Loss of cell cycle control → ↑ proliferation.
• Low-risk types (6, 11) → LSIL + condylomas:
  • Viral genome does NOT integrate (episomal); productive infection.

6. Invasive Cervical Carcinoma

Types

• Squamous cell carcinoma (75 %)
• Adenocarcinoma (~20 %)
• Small cell neuroendocrine carcinoma (~5 %)

A) Squamous cell carcinoma

• Virtually all are HPV-associated; arise from HSIL.
• Peak incidence: 45 yr.
• Advanced → pain, bleeding, painful intercourse.
• Risk factors: early intercourse, HPV-infected partner, history of HSIL, smoking, high-risk HPV.
• Prognostic factors: clinical stage, tumor size, depth of invasion, nodal status, endometrial extension.
• Tx: surgery + radiation + radioactive implants (brachytherapy).

B) Adenocarcinoma

• Majority HPV-associated; precursor = in-situ adenocarcinoma.
• Non-HPV variants (clear cell, mesonephric, gastric type) → aggressive.
• Sx: vaginal bleeding, pelvic pain.
• Spread: pelvic structures → pelvic LN → ovaries, upper abdomen, distant.
• Survival by stage: I = 79 %, II = 37 %, III/IV < 9 %.
• Gross: exophytic mass / ulcerated plaque / barrel-shaped cervix.
• Micro: often well-differentiated, papillary, endometrioid.

7. Progression Pathway

Normal → HPV infection (koilocytosis) → CIN I (LSIL) → CIN II/III (HSIL) → invasive carcinoma

• LSIL → 70 % regress spontaneously.
• HSIL → higher progression risk to invasive cancer over years.

💡 High-yield: Cervix cancers arise at squamocolumnar junction (transformation zone). HPV high-risk (16, 18, 31, 45) → integrates → E6 inactivates p53, E7 inactivates RB → HSIL + invasive SCC. HPV low-risk (6, 11) = condylomas + LSIL (episomal, no integration). CIN I = LSIL with koilocytes; CIN II/III = HSIL. Pap smear = most successful cancer screening test. SCC (75 %) + adenocarcinoma (20 %) + small cell (5 %). Risk: early intercourse, multiple partners, smoking, persistent high-risk HPV.