Value of combining HPV-DNA testing with follow-up Papanicolaou smear in patients with prior atypical squamous cells of undetermined significance

OBJECTIVE: To address human papillomavirus (HPV) testing on negative Pap tests preceded by atypical squamous cells of undetermined significance (ASC-US) without reflex HPV testing. STUDY DESIGN: Positive HPV test results with concurrent negative Pap tests over 1 year were identified. Pathology records for all patients diagnosed with ASCUS without reflex HPV testing in the previous year were reviewed; all cytologic and surgical specimens over the subsequent 2 years were evaluated for squamous abnormalities. RESULTS: Fifty patients had positive HPV DNA (HPV-DNA) test result combined with a negative Pap test. Twenty-three had a previous Pap test interpretation of ASC-US (without HPV testing) within the preceding year. On follow-up, 8 of 23 developed a squamous intraepithelial lesion (SIL) within 1 year. Four additional cases developed SIL in the second year after positive HPV testing. All dysplasias in the first year of follow-up were low grade; 1 of 4 developing in the second year was high grade. CONCLUSION: Negative Pap smear following an ASC-US interpretation without a concurrent HPV test is associated with significant false negative rate. We suggest consideration of combining HPV-DNA testing to all initial follow-up negative Pap tests of patients with previous ASC-US, if reflex HPV testing has not been performed.