Risk factors for HR-HPV persistence and residual or recurrent high-grade squamous intraepithelial neoplasia after LEEP

Background To investigate factors associated with persistent high-risk human papillomavirus (HR-HPV) infection and residual or recurrent disease in patients with high-grade squamous intraepithelial lesions (HSIL) following loop electrosurgical excision procedure (LEEP). Methods A total of 903 patients with pathologically confirmed HSIL who underwent LEEP between January 2021 and May 2024 were retrospectively enrolled. HR-HPV genotyping and cervical cytology were performed before and after surgery, and residual or recurrent HSIL was assessed by colposcopy during follow-up. Generalized estimating equation (GEE) logistic regression accounted for within-patient clustering of genotype-specific HPV observations. Multivariable logistic regression identified factors associated with HR-HPV persistence, and Firth's penalized logistic regression evaluated factors associated with residual or recurrent HSIL. Results Persistent HR-HPV infection rates were 23.3%, 19.0%, and 17.5% at 6, 12, and 18 months after LEEP, respectively. GEE analysis showed significant differences in type-specific persistence among the α 5/6, α 7, and α 9 species ( P = 0.024), with higher persistence in α 5/6 than α 7 (27.1% vs. 14.0%; OR = 2.30, 95% CI, 1.09–4.85; adjusted P = 0.024), but no significant differences between α 5/6 and α 9 or between α 7 and α 9. Multiple HR-HPV infections (OR = 2.76, 95% CI, 1.96–3.89; P < 0.001) and menopausal status (OR = 2.06, 95% CI, 1.18–3.66; P = 0.011), and positive endocervical margins (OR = 2.54, 95% CI, 1.48–4.32; P = 0.007) were associated with HR-HPV persistence. During follow-up, 32 patients (3.5%) developed residual or recurrent HSIL (21 residual, 11 recurrent). Firth's penalized regression identified persistent type-specific HR-HPV infection (OR = 21.88, 95% CI, 8.25–72.76; P < 0.001), number of involved cervical quadrants ( P = 0.025), endocervical involvement ( P = 0.006), and surgical margin status ( P < 0.001) as independently associated with residual or recurrent HSIL. Conclusions α 5/6 species showed a higher type-specific HR-HPV persistence than α 7 but not α 9 following LEEP. Multiple HR-HPV infections, menopausal status, and positive endocervical margins were associated with HR-HPV persistence. Persistent type-specific HR-HPV infection, multiple involved cervical quadrants, endocervical involvement, and positive surgical margins were independent predictors of residual or recurrent HSIL. Multicenter studies are warranted to validate integrating margin status with HPV genotyping for postoperative risk stratification.