ASC/SIL Ratio Benchmarks Should be Stratified by Human Papillomavirus Status

Summary: Introduction: The College of American Pathologists' accreditation requires laboratories to monitor, as a quality benchmark, the ratio of atypical squamous cells interpretations (ASC) to squamous intraepithelial lesion or higher interpretations (SIL) for gynecologic cytology specimens and further requires corrective actions for laboratories with ratios outside benchmarks. Human papillomavirus (HPV) status and HPV vaccination status are known risk factors for cervical dysplasia, but ASC/SIL ratio benchmarks are not currently stratified by these risk factors. We sought to understand if HPV status or HPV vaccination status affected our ASC/SIL ratio. Materials and Methods: Gynecologic cytology specimens from our laboratory in 2023 were included in the study. We excluded cases interpreted as positive for endometrial carcinoma. We calculated our laboratory's ASC/SIL ratios by HPV status and HPV vaccination status and compared those to our overall ASC/SIL ratio. We used chi-squared tests to compare proportions of patient populations and set p-value to 0.05. Results: The overall ASC/SIL ratio was 3.00. In comparison, our ASC/SIL ratio was 2.24 for HPV positive patients (p=0.10) and 8.19 for HPV negative patients (p=8.4 x10-6) (Table 1). By HPV vaccination status, our ASC/SIL ratio was 2.93 for non-vaccinated patients (p=0.87), 3.22 for patients with any HPV vaccination (p=0.75), and 3.18 for patients with complete HPV vaccination (p=0.82) (Table 2). Conclusions: We find the ASC/SIL ratio statistically higher for HPV negative patients compared to the patient population. However, we find no statistical difference in ASC/SIL ratio for patients based on vaccination status. Given our findings that HPV status affects ASC/SIL ratio, the heterogeneity of HPV status between laboratories' patient populations, and the ease of finding patients' HPV statuses, we propose that ASC/SIL ratios benchmarks be stratified by HPV status going forward. This will better elucidate which laboratories truly require corrective action for their interpretations of gynecologic specimens, without the confounding effects of HPV status.