With human papillomavirus (HPV) testing, patients' HPV status may be known when reviewing cytology specimens.
41,955 women 25 years or older had cytology and HPV screening. Originally, cytology was reviewed blinded to HPV status. We re-reviewed unblinded to HPV status a subset of 428 cytology slides from women with cervical intraepithelial neoplasia grade 2 + (CIN2+) and 1,287 from women without CIN2+.
Of the original interpretations of atypical squamous cells of undetermined significance (ASC-US), 33.7% were downgraded to negative after unblinded review, and 8.7% were upgraded to atypical squamous cells, cannot rule out a high-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Of the original interpretations of ASC-US, 66.7% were downgraded on unblinded review in HPV-negative women and 30.2% were upgraded in HPV 16+/HPV 18+ women. Unblinding increases the sensitivity for cervical intraepithelial neoplasia grade 3+ of cotesting from 54.1% to 62.4% (P = .0015) and the sensitivity of HPV primary screening from 72.2% to 77.1% (P = .0029). With cotesting, specificity with unblinding is improved, whereas with HPV primary screening, there would be a small decrease in specificity.
Unblinded cytology increases overall sensitivity with either cotesting or HPV primary screening; specificity is either slightly improved or is not affected by unblinding.