HPV positivity in cervical cancer screening facilitates increased cytology sensitivity The vast majority of cytology examiners in randomized controlled studies are unaware of HPV status. This study, published in JNCI, is the Chao sub-study of the NTCC Randomized Controlled Study. Women aged 25-60 years in the study were referred for colposcopy if they were HPV positive and followed up until HPV negative if colposcopy did not reveal CIN. Cytologic smears from the first colposcopy were sent for independent evaluation to a laboratory outside the study center, which was informed only about the patient’s HPV positivity. The study objectives were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of CIN2+ in women with cytology of ASCUS or worse. The results found that the sensitivity, specificity, PPV, and 1-NPV of cytology for the diagnosis of CIN2+ in a cross-section of HPV-positive women were 85.6%, 65.9%, 16.2%, and 1.7%, respectively. Cytologic findings were also associated with the risk of subsequent new diagnosis of CIN2+ and CIN3+. For cytology with ≥ASCUS, the relative sensitivity of knowing HPV status compared with cytology without HPV status was 1.58 (95% CI 1.22-2.01) and the relative rate of referral for colposcopy was 0.95 (0.86-1.04). The study concludes that cytology to know the rate of HPV positivity is more sensitive than blinded cytology, and also allows for a longer interval between tests in HPV-positive, cytology-negative women.