Precancer of the uterine cervix. Cervical intraepithelial neoplasia (CIN). Importance of early diagnostic methods - cytology, histology.
Most cervical lesions are harmless inflammations, but cervical carcinoma is also one of the most common forms of cancer.
Most cervical cancers are epithelial in origin and caused by oncogenic strains of human papillomavirus (HPV). HPV is selective for immature squamous cell of the transformation zone, where squamous epithelial cells and mucus secreting epithelial cells both exist.
Most HPV infections are eradicated quickly without issue, however, some form a precursor lesion. The infection occurs at the most immature squamous cells at the basement membrane, however HPV DNA replication occurs in the overlying squamous cells thanks to expression of two oncoproteins, E6 and E7 that promote growth. Different infections can be high or low risk for development of Cervical Intraepithelial Neoplasia (CIN), HPV 16 and 18 account for 70% of cases.
Memory aid: E6 and E7 switch off the two key tumour suppressors: E6 degrades p53 and E7 binds and inactivates RB. High-risk types (16, 18) make E6 and E7 that do this much more strongly than low-risk types (6, 11), which cause genital warts.
CIN is HPV related carcinogenesis changes, which have three categories:
- CIN I - low grade dysplasia
- Found in lower third of squamous epithelium and koilocytotic change in superficial layers
- CIN II - moderate dysplasia
- Dysplasia extends upwards, affecting bottom ⅔ now, takes form of delayed keratinocyte maturation
- CIN III - severe dysplasia
- Marked by complete cell atypia
This dysplasia can be observed on smears, and early detection of the dysplasia allows us to catch cervical cancer early. Recently a vaccine has been introduced for HPV which is highly effective. CIN is asymptomatic and only comes to attention through a smear test.
Pap smear: normal squamous cells with small nuclei (left); HPV-infected koilocytes with enlarged, dark, wrinkled nuclei, a clear halo around the nucleus and two nuclei (right), as in CIN I / LSIL.
Image: “ThinPrep Pap smear HPV” by Photomicrograph by Ed Uthman, MD. 20 July 2006 Euthman 20:24, 29 November 2006 (UTC), CC BY-SA 2.0, via Wikimedia Commons.