Validation of HPV triage in cytology-based cervical cancer screening for ASC-US cases using Japanese data

Objective: In Japan, cervical cancer screening consists of a cytology examination performed once every 2 years. We verified whether the risk of cervical intraepithelial neoplasia (CIN) 3 disease or higher (CIN3+) was equivalent to that of cytology negative cases (negative for intraepithelial lesion or malignancy [NILM]) for patients with a cytological diagnosis of “atypical squamous cells of undetermined significance (ASC-US)” who tested negative for human papillomavirus (HPV). Methods: Data from a total of 22,925 cases who had undergone cervical cancer screening at least twice or who had completed follow-up examinations after cervical screening at a single facility between April 2013 and April 2018 were analyzed. The cumulative incidence of CIN3+ was calculated for each category of initial cytology finding and HPV result (NILM, > ASC-US, ASC-US/HPV (unknown), ASC-US/HPV⁺, and ASC-US/HPV⁻). The statistical analysis was conducted using the Cox proportional hazards model. Results: The hazard ratio for the cumulative incidence of CIN3+ in 2 years relative to that for NILM cases was 2.7 (95% confidence interval=1.0–7.8) for > ASC-US cases, 0.5 (0.1–1.7) for ASC-US/HPV (unknown), 0.8 (0.3–2.4) for ASC-US/HPV⁺ cases, and 0.3 (0.1–1.0) for ASC-US/ HPV⁻ cases. Conclusion: Because the cumulative incidence of CIN3+ at 2 years for the ASC-US/HPV⁻ cases was sufficiently low, compared with that of the NILM cases, we considered it reasonable and safe to perform HPV triage for ASC-US cases and to allow HPV-negative cases to return for their next screening in 2 years, which is the same follow-up schedule as that for NILM cases.