Approximately 1% to 2% of routine cytologic specimens collected for Papanicolaou testing are unsatisfactory for evaluation. The American Society for Colposcopy and Cervical Pathology 2019 guidelines recommend repeat testing within 2 to 4 months of an unsatisfactory Papanicolaou test (UPT) result.
We evaluated the utility of follow-up Papanicolaou testing, human papillomavirus (HPV) testing, and biopsy in 258 cases of UPTs.
High-risk HPV testing was positive in 17.4% (n = 45) and negative in 82.6% (n = 213) of cases at the time of initial UPT; 8.1% (n = 21) of cases had discordant HPV test results. Similarly, 3.8% (n = 8) of initially HPV-negative cases were reported to be HPV-positive on follow-up; 28.9% (n = 13) of initially HPV-positive cases were reported to be HPV negative on follow-up. In total, 27.1% (n = 70) of cases underwent biopsy. Biopsies with significant findings were present in 40% (n = 12) of HPV-positive cases and 7.5% (n = 3) of HPV-negative cases. Low-grade squamous intraepithelial lesion (LSIL) (low-grade cervical intraepithelial neoplasia [CIN-1]) was the most significant finding in all 3 HPV-negative biopsies; 58.3% (n = 7) of HPV-positive biopsies showed LSIL (CIN-1), 13.3% (n = 4) showed HSIL (high-grade CIN), and 3.3% (n = 1) showed invasive carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of concurrent HPV testing at the time of UPT for predicting follow-up HPV test result within 1 year of initial UPT are 80.0%, 94.0%, 71.1%, and 96.2%, respectively. The sensitivity, specificity, PPV, and NPV of initial HPV test results for predicting follow-up Papanicolaou test results are 67.7%, 89.7%, 48.8%, and 95.0%, respectively.
Concurrent HPV testing in the setting of UPT can be a sensitive tool for predicting follow-up HPV status and significant findings of squamous intraepithelial lesions on follow-up Papanicolaou tests and biopsy.

© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.