Cytomorphological clues and progression potential according to high-risk human papillomavirus types in low-grade...

Low-grade squamous intraepithelial lesions (LSILs) are frequently associated with human papillomavirus (HPV) infections; however, the cytomorphological differences among high-risk HPV (HR-HPV) genotypes remain underexplored. In this retrospective study, we aimed to assess whether LSIL cytological features differed between HPV16/18 and other HR-HPV types and evaluated the impact of genotypes on 1-year clinical outcomes.

In total, 9,184 cervical smears reviewed over 3 years yielded 191 LSIL cases. Of the 137 patients with positive HPV polymerase chain reaction results, 110 (36 with HPV16/18 and 74 with other HR-HPV) met the inclusion criteria. Two pathologists, blinded to clinical and genotype information, independently evaluated 13 cytological criteria. Intraepithelial lesions or malignancies that regressed to negative for intraepithelial lesion or malignancy (NILM) or progressed to high-grade squamous intraepithelial lesions (HSIL) were analyzed over 1 year.

Hyperchromasia (72.2% vs. 47.3%, P = 0.014) and nuclear contour irregularities (100% vs. 87.8%, P = 0.029) were significantly more frequent in the HPV16/18 cohort. Conversely, anisonucleosis (71.6% vs. 50%, P = 0.026) and marked nuclear enlargement (>5× intermediate cell nuclear diameter; 29.7% vs. 8.3%, P = 0.012) were predominant in the other HR-HPV cases. Regression to NILM occurred in 11.1% of the HPV16/18 group and 37.8% of the other HR-HPV group (P = 0.004), with a longer mean time to regression in the HPV16/18 group (10.93 vs. 9.12 months; P = 0.014). HSIL progression was more frequent (27.8% vs. 4.1%; P <0.001) and occurred earlier (9.01 vs. 11.53 months; P <0.001) in the HPV16/18 group.

LSILs associated with HPV16/18 are characterized by hyperchromasia and contour irregularities, whereas other HR-HPV infections are characterized by nuclear enlargement and anisonucleosis. These genotype- specific cytomorphological clues may strengthen cytology-based triages, particularly in settings where HPV testing is limited.