Diagnostic performance of cervical cytology in HPV-independent cervical cancer: a comparative analysis with...

This study evaluated the diagnostic accuracy of cervical cytology (Pap test) in human papillomavirus (HPV)-independent (HPVI) cervical cancers compared to that in HPV-associated (HPVA) cancers, and investigated differences in clinical outcomes.

We retrospectively reviewed the medical records of 515 patients diagnosed with cervical cancer between 2000 and 2021. The patients were categorized as HPVA (n=439) or HPVI (n=76) cervical cancer groups based on pathology and HPV testing. Cytology results were reclassified into 3 clinical categories: negative, low-grade abnormal, and high-grade abnormal. Multivariable logistic regression analyses were performed adjusting for age, stage, tumor size, lymphovascular space invasion, and parametrial invasion. Subgroup analyses were conducted in adenocarcinoma and HPVA cohorts. Survival outcomes were evaluated using Kaplan-Meier analysis and compared using log-rank tests.

HPVI cancers showed a significantly higher rate of false-negative cytology results (39.5%) than HPVA cancers (18.0%, p<0.001). High-grade cytological abnormalities were less common in HPVI cases (52.6% vs. 69.2%). Similar trends were observed in adenocarcinoma-only cases, although the differences were not significant (39.5% vs. 22.8%, p=0.055). In multivariable analyses adjusting for clinicopathologic factors, HPVI status remained significantly associated with higher odds of negative cytology (adjusted odds ratio=3.04; 95% confidence interval=1.60-5.78). The Kaplan-Meier analysis demonstrated significantly worse progression-free and overall survival in patients with HPVI cancers (p<0.001).

Cervical cytology demonstrated lower sensitivity for detecting HPVI cervical cancers, which are also associated with more aggressive clinical features and poorer outcomes. These findings support the need for tailored screening strategies for this underdetected cancer subtype.