Abstract
BACKGROUND The clinical significance of high-risk human papillomavirus (HR-HPV)-negative high-grade cervical intraepithelial neoplasia remains unclear. A negative HR-HPV test result can stem from assay limitations (e.g., low viral load, non-covered types) or biological factors (e.g., viral clearance, true HPV-independent pathways). This study aimed to compare recurrence and hysterectomy rates between HR-HPV-positive and HR-HPV-negative women in a cohort of 712 women who underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3). MATERIAL AND METHODS This retrospective, multicenter cohort study analyzed data from 712 women with a histopathological diagnosis of CIN3 between 2014 and 2023. HR-HPV detection and genotyping were performed using the Cobas 4800 (Roche HPV assay) test. A review of patient records was conducted, and statistical analyses included Kaplan-Meier survival estimates and Cox proportional hazards regression models. RESULTS In our cohort of 712 women with CIN3, 9% (n=64) were HR-HPV-negative. The primary finding was that HR-HPV-negative status showed no significant association with the risks of recurrence, progression to cancer, or hysterectomy compared to HR-HPV-positive cases. Specifically, recurrence rates (6.2% vs 12.1%) and the incidence of cervical cancer (2% vs 1.5%) were comparable, with no statistically significant differences (p>0.05 for both). CONCLUSIONS HR-HPV-negative CIN3 is a clinically significant entity that requires management and follow-up equivalent to HR-HPV-positive CIN3, as it demonstrates comparable oncologic outcome.