Squamous and Glandular Precancerous Lesions of the Cervix: A Series of Five Cases based on LAST and WHO 2020 Classifications

Cervical cancer is a gynaecological malignancy whose incidence and mortality can be significantly reduced through effective screening programs. Precancerous lesions of the cervix comprise a broad morphological spectrum, including squamous and glandular abnormalities, which require careful evaluation with histopathology, immunohistochemistry, and Human Papillomavirus (HPV) testing. Here the author presents a series of five cases: Cervical Intraepithelial Neoplasia grade 1 (CIN-1), Cervical Intraepithelial Neoplasia grade 2 (CIN-2), Cervical Intraepithelial Neoplasia grade 3 (CIN-3), Adenocarcinoma In Situ (AIS), and Stratified Mucin-producing Intraepithelial Lesion (SMILE) diagnosed in the clinic. The novelty of this series lied in presenting both squamous and glandular precancerous lesions, including rare variants such as SMILE, within a single case series. This comprehensive approach highlights the diagnostic diversity and underlines the practical application of current WHO and LAST classification systems. The diagnostic work-up of each case included cytological evaluation, colposcopy, haematoxylin and eosin histopathology, and immunohistochemical studies with tumor suppressor protein (p16) and Antigen Kiel 6 (Ki-67). Case 1 involved a 47-year-old woman with HPV type 18 infection and Atypical Squamous Cells of Undetermined Significance (ASC-US), diagnosed as CIN-1 with weak focal p16 expression, showing spontaneous regression on follow-up. Case 2 was a 45-year-old woman positive for HPV type 16, who exhibited diffuse strong p16 and Ki-67 expression, consistent with CIN-2, for which conisation was planned. Case 3 involved a 34-year-old woman with HPV type 16, who showed full-thickness dysplasia and glandular involvement, diagnosed as CIN-3 (high-grade squamous intraepithelial lesion), requiring repeat conisation. Case 4 was a 43-year-old woman with HPV types 16 and 68, who demonstrated coexistence of CIN-1 and AIS with strong p16 expression, and underwent total laparoscopic hysterectomy with bilateral salpingectomy. Case 5 involved a 46-year-old woman positive for HPV type 16, showing mucin-containing dysplastic cells consistent with SMILE, managed by close follow-up. These cases illustrate the diagnostic spectrum of cervical precancerous lesions, highlight the importance of immunohistochemical markers in differential diagnosis, and emphasise the clinical significance of the 2020 World Health Organisation (WHO) classification in distinguishing HPV-associated and HPV-independent lesions. Accurate diagnosis through a multidisciplinary approach enables personalised management, thereby preventing progression to invasive cervical cancer.