Question
Cervical intra epithelial neoplasia
Answer
Cervical intraepithelial neoplasia (CIN) is a precursor lesion of cervical squamous cell carcinoma, caused by persistent infection with high-risk HPV types (especially 16, 18), characterized by dysplastic squamous epithelial changes confined above the basement membrane.
Grading (based on the extent of full-thickness epithelial replacement by immature, atypical cells):
- CIN I (mild dysplasia): Atypical, immature basaloid cells confined to the lower third of the epithelium; koilocytotic changes often present in the upper layers (reflecting productive HPV infection); most regress spontaneously — considered a low-grade squamous intraepithelial lesion (LSIL).
- CIN II (moderate dysplasia): Atypia extends to the lower two-thirds of the epithelium; a high-grade squamous intraepithelial lesion (HSIL).
- CIN III (severe dysplasia/carcinoma in situ): Atypia involves greater than two-thirds to the full thickness of the epithelium, with loss of maturation, increased nuclear-cytoplasmic ratio, hyperchromasia, and abnormal mitoses throughout; also HSIL; a true precursor for invasive carcinoma if untreated.
Pathogenesis: HPV E6 and E7 oncoproteins inactivate p53 and Rb tumour suppressor proteins respectively, driving uncontrolled proliferation and genomic instability.
Clinical relevance: Detected via Pap smear screening (showing dysplastic squamous cells) and confirmed by colposcopy-directed biopsy; HSIL (CIN II/III) requires treatment (excision/ablation, e.g., LEEP) to prevent progression to invasive squamous cell carcinoma.