Something old, something new: Cervical cytopathology in the new era

Papanicolaou (Pap) smear on cervical cells heralded the revolution of modern cytopathology in the middle of the 19th century, and cervical screening is now considered one of medicine’s greatest success stories. While routine cervical cytology has significantly reduced the incidence of cervical cancer worldwide, it is not without limitations. Although the specificity of Pap smear to detect high-grade intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2–3 is consistently high, the sensitivity ranges broadly from 34 % to 94 % [1]. Given the rapid evolution in understanding the etiologic role of high-risk human papillomavirus (hrHPV) in cervical cancer development, the clinical guidelines have transitioned from “evidence-based” to “risk-stratified” algorithms. Primary hrHPV testing as a more sensitive test for high-risk cervical lesion (CIN2+) detection is considered the preferred screening test in some guidelines, but due to its low specificity, a follow-up triage test is needed to reduce unnecessary colposcopy referrals. Candidates for the triage test include cytology, biomarkers such as P16/Ki67 dual stain (DS), and hrHPV genotyping. This review discusses the advantages and potential issues with primary hrHPV testing and dual stain, the current American Society of Colposcopy and Cervical Pathology (ASCCP) guideline with a focus on new endocervical curettage (ECC) guidelines, as well as the new World Health Organization (WHO) classification of endocervical adenocarcinoma and the impact on cervical cytopathology.