HPV positivity despite cytological negativity: Risk assessment with colposcopic and histopathological findings

To evaluate agreement between colposcopy-directed histopathological findings and final histopathological diagnoses in women with negative cytology but positive high-risk human papillomavirus (HR-HPV), and to assess associations of HPV genotypes with concordance and recurrence.

This retrospective study included women aged ≥18 years with negative cytology and HR-HPV positivity who underwent colposcopy at a tertiary center between January 2020 and January 2025. Histopathological results were obtained from endocervical curettage (ECC), biopsy, or conization. Concordance was defined as agreement between colposcopy-directed histopathological findings and the final histopathological diagnosis. Patients were followed for at least 12 months, with recurrence defined as histopathological detection of LSIL/HSIL or re-detection of HR-HPV during follow-up.

A total of 222 women were included (median age: 44 years). Overall concordance was 53.2%. HPV16-positive women had lower concordance than HPV16-negative women (46.7% vs. 60.8%, p=0.036). HPV18, single-type, and multiple-type HR-HPV were not associated with concordance (all p>0.05). Recurrence occurred in 24.0% of patients with available follow-up data (n=125), with no significant association with HPV genotype.

Colposcopy-directed histopathological assessment shows moderate agreement with final histopathology in cytology-negative, HR-HPV-positive women. HPV16 positivity may be associated with lower concordance, while HPV genotype was not associated with recurrence. Careful follow-up may be warranted, and larger prospective studies are needed to confirm these findings.