Risk of HSIL/CIN2+ Lesions in Women with Negative Cytology and High-Risk HPV Referred to Colposcopy: Experience in a Population-Based Screening Program.

OBJECTIVE

To assess the prevalence of HSIL/CIN2+ lesions in women with negative cytology and high-risk HPV (HR-HPV) referred to colposcopy from population-based screening, as well as to describe histological findings and the need for excisional treatment.

METHODS

Prospective observational study (November 2022-June 2025). Included were women referred to colposcopy with negative cytology and positive HR-HPV results: (1) HPV16/18, (2) persistent non-16/18 HR-HPV, (3) HPV16/18 + HR-HPV co-infection, and (4) non-16/18 HR-HPV infection evolving to HR + 16/18 co-infection after one year. Clinical data, histological outcomes, and excisional procedures were analyzed.

RESULTS

A total of 519 women were studied (mean age 50.9 years). Distribution: HPV16/18 (55.2%), non-16/18 HR-HPV (34.9%), co-infection (9.1%), and non-16/18 HR-HPV evolving to HR + 16/18 co-infection (0.8%). Among exocervical biopsies (n=276), 37 showed HSIL and 2 carcinomas were identified. In endocervical samples (n=476), 6 HSIL and 1 carcinoma were detected. Excisional treatment was performed in 42 women, revealing 19 HSIL, 1 adenocarcinoma, and 1 squamous carcinoma. The overall prevalence of HSIL/CIN2+ was 9.6%, higher in women with HPV16/18 (13.6%) compared to non-16/18 HR-HPV (4.9%), RR=2.76 (95% CI: 1.37-5.56; p<0.05).

CONCLUSIONS

Detection of HR-HPV identifies clinically significant lesions even in women with negative cytology. Our findings support immediate colposcopy in HPV16/18-positive cases and close follow-up in persistent infections with other HR-HPV genotypes.