Patients who still carried the same high-risk human papillomavirus genotype after LEEP were far more likely to have residual or recurrent HSIL during follow-up, according to a retrospective study of 903 patients. The finding points to persistent, type-specific HPV as a possible marker of higher postoperative risk, but it does not show that the virus caused the later disease.
The study tracked patients with histologically confirmed HSIL who underwent LEEP at one hospital in Shanghai between January 2021 and May 2024. They were included if they had HPV genotyping before and after surgery, at least 18 months of follow-up and at least two completed visits.
Persistence fell, but did not disappear
High-risk HPV persistence was found in 210 patients, or 23.3%, at six months. The proportion fell to 19.0% at 12 months and 17.5% at 18 months, when 158 patients still met the study’s persistence definition. Over the 18-month follow-up, 32 patients, or 3.5%, developed residual or recurrent HSIL.
For the study, type-specific persistence meant that an identical HPV genotype was detected before surgery and again at six months. Follow-up included cytology at three months, HPV and cytology testing at six months, and further assessments every six months for at least 18 months. Residual disease was biopsy-confirmed HSIL within six months, while recurrence was confirmed more than six months after surgery following initially negative or normal findings.
The virus groups did not behave identically. Estimated persistence was 27.1% for the α5/6 species group, compared with 18.8% for α9 and 14.0% for α7. Persistence in α5/6 was higher than in α7, with an odds ratio of 2.30 and an adjusted P value of 0.024. The comparisons involving α9 were not statistically significant.
Multiple infections were also more common in some groups: 74.7% for α5/6 and 71.4% for α7, compared with 44.1% for α9. The overall difference was statistically significant, while α7 and α5/6 did not differ significantly from each other.
Several features tracked with persistent infection
Patients with multiple high-risk HPV infections had 2.76 times the odds of persistence compared with those with a single infection. Postmenopausal patients had 2.06 times the odds compared with premenopausal patients, and a positive endocervical margin was associated with 2.54 times the odds compared with a negative margin.
The study also linked persistent type-specific HPV with residual or recurrent HSIL. Other associated features included involvement of multiple cervical quadrants, endocervical involvement and surgical margin status. In the final model, persistent HPV had an odds ratio of 21.88, CIN2-3 endocervical involvement had an odds ratio of 4.95, and basal margin involvement had an odds ratio of 40.60.
Among the 32 patients with residual or recurrent disease, 21 cases were classified as residual and 11 as recurrent. Persistent HPV was common in both groups, occurring in 85.7% of residual cases and 90.9% of recurrent cases. Positive margins were more frequent in residual disease, at 81.0%, than in recurrent disease, at 45.5%, but neither comparison was statistically significant.
What the findings can and cannot say
The researchers used regression methods that accounted for the fact that several HPV genotypes could come from the same patient. They used a penalized regression model for residual or recurrent HSIL because there were only 32 outcome events. The study was observational, so these associations do not establish causal effects.
The evidence is limited by the study’s single-center retrospective design, which can introduce selection bias and may not represent other populations. The follow-up may be too short to measure long-term recurrence, and the small number of outcome events led to sparse categories and imprecise estimates. The analysis also cannot establish whether six-month HPV persistence came before residual disease diagnosed before that assessment.
The authors linked multiple HPV infection, menopausal status and positive endocervical margins with persistence, and linked persistent type-specific HPV, multiple cervical quadrants, endocervical involvement and positive margins with residual or recurrent HSIL. They called for prospective multicenter validation.
The work was supported by university, municipal, district, clinical-research and national clinical-specialty programs. The authors said raw data supporting the conclusions would be made available without undue reservation.
Paper data and sources
Original title: Risk factors for HR-HPV persistence and residual or recurrent high-grade squamous intraepithelial neoplasia after LEEP
Authors: Wang L, Zhang Y, Chen Y et al.
Journal/Repository: Frontiers in medicine
Status: Peer-reviewed
First online: 2026-10-09
DOI: Not available
Original paper · Full text