Follow-up of Women Testing Positive for Human Papillomavirus Non-16/18 With Normal Cytology in a Screening Context

Objective The aim of the study was to evaluate the risk for cervical intraepithelial neoplasia II (CIN 2) or worse associated with high-risk (HR) non-16/18 human papillomavirus (HPV) types among women with normal cytology in a screening context. Methods This population-based historical cohort study was conducted in a large state-mandate health provider. Human papillomavirus genotyping was performed on Pap tests collected in women that were positive for non-16/18 HPV types from 2019 to 2023. HPV detection was performed using COBAS (4800/6800) (Roche Diagnostics) test: a qualitative in vitro test for the detection of 14 HR HPV types. The women were followed for histopathologic outcomes until end of 2024. Cumulative incidence proportions of CIN 1, 2, and 3 or worse were calculated. Results Of 24,439 women tested positive for HPV during the study period, a total of 7,930 women tested positive for HR HPV non-16/18 with a normal cytology. Among these, 875 (11.1%) developed pathological findings in biopsy including CIN II ( n = 68, 0.9%) and CIN III ( n = 802, 10.1%) lesions, cervical squamous cell carcinoma and adenocarcinoma (4, 0.1%), as well as one case of adenocarcinoma in situ (0.01%). Conclusions Women with HR HPV non-16/18 and normal cytology represent a high-risk group requiring long-term follow-up. No malignancies were observed in the first year of follow-up, supporting the recommendation for retesting after 12 months and colposcopy referral if the infection persists.