First principle: persistent high‑risk HPV at the transformation zone
The transformation zone (squamocolumnar junction) is where nearly all cervical neoplasia arises. Oncogenesis is driven by two viral proteins: E6 → degrades p53; E7 → inactivates Rb. Cytological footprint: the koilocyte.
Terminology: don't mix cytology with histology
| Cytology (Bethesda, smear) | Histology (biopsy) |
|---|---|
| LSIL | CIN 1 |
| HSIL | CIN 2/3 |
Histology = squamous cell carcinoma most commonly; adenocarcinoma arises from endocervical glandular epithelium.
Presentation
Often asymptomatic early. Classic: postcoital bleeding, intermenstrual/abnormal bleeding, watery/offensive discharge, later pelvic pain/dyspareunia. Postcoital bleeding → think cervix.
Staging (modern update)
FIGO is now clinical + imaging/pathology where available. High‑yield modern change: Stage IIIC = nodal disease — IIIC1 pelvic, IIIC2 para‑aortic. 🚩 (Conceptually: I confined to cervix; II beyond cervix, not pelvic wall/lower‑third vagina; III lower‑third vagina/pelvic wall/hydronephrosis/nodes; IV bladder‑rectum or distant.)
Management logic
- Pre‑invasive/early: excisional treatment (LLETZ/cone); fertility‑sparing trachelectomy in selected invasive cases; radical hysterectomy + nodal assessment.
- Locally advanced: concurrent chemoradiation + brachytherapy (platinum radiosensitiser).
- Advanced/recurrent: now includes immunotherapy/targeted agents (e.g. pembrolizumab, bevacizumab) in selected patients.
Pitfalls
- Confusing a smear (cytology) result with a tissue diagnosis; a smear screens, biopsy diagnoses.
- Forgetting nodal disease is now Stage IIIC.
Pearls
- 🎯 Persistent hrHPV (16,18) → E6/p53, E7/Rb → CIN → SCC. Postcoital bleeding = cervix. IIIC = nodes.
- 🩺 Locally advanced disease → chemoradiation + brachytherapy, not primary surgery.
Next → Because we know the cause, we can prevent it (Concept 39).