Question
Pathogenesis and screening methods of carcinoma cervix
Answer
Pathogenesis: Cervical carcinoma (predominantly squamous cell carcinoma) results from persistent infection with high-risk human papillomavirus (HPV) types, especially HPV 16 and 18. HPV oncoproteins E6 and E7 inactivate the tumour suppressor proteins p53 and Rb respectively, driving loss of cell cycle control, genomic instability, and uncontrolled proliferation of cervical squamous epithelium. This progresses through a well-defined precursor sequence: cervical intraepithelial neoplasia (CIN I → II → III), representing increasing grades of dysplasia, before progressing to invasive carcinoma if untreated. Cofactors include multiple sexual partners, early coitarche, smoking, immunosuppression (e.g., HIV), and lack of HPV vaccination.
Screening methods:
- Papanicolaou (Pap) smear/cytology: Conventional or liquid-based cytology examining exfoliated cervical cells for dysplastic changes (nuclear enlargement, hyperchromasia, koilocytosis); mainstay of population screening, typically recommended every 3 years from age 21 (or per national guidelines).
- HPV DNA testing: Detects high-risk HPV types directly; more sensitive than cytology alone; often used in co-testing with Pap smear or as primary screening in women over 30.
- Visual inspection with acetic acid (VIA): Low-resource-setting alternative — application of acetic acid to the cervix highlights dysplastic areas as aceto-white lesions, visible on direct inspection.
- Colposcopy with directed biopsy: Performed as a follow-up to an abnormal screening test, for magnified visual examination and histological confirmation of the cervix.
Effective screening programmes, combined with prophylactic HPV vaccination, have substantially reduced the incidence and mortality of cervical cancer by detecting and treating precursor CIN lesions before progression to invasive disease.