Objective To compare the results from an initial negative human papillomavirus ( HPV ) test with re‐screening after 3 years in women attending two HPV ‐based screening programmes. Design Population‐based cohort study. Setting Two cervical service screening programmes in Italy. Population Women aged 25–64 years invited to screening from April 2009 to October 2015. Methods Eligible women were invited to undergo an HPV test. Those with a negative HPV test went on to the next screening round 3 years later. Cytology triage was performed for HPV + ( HPV by Hybrid Capture 2) samples, with immediate colposcopy (if abnormal) and HPV re‐testing 1 year later (if negative). Main outcome measures Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ ( CIN 2+) at colposcopy, and detection rate for CIN 2+. Results We present the results from 48 751 women at the first screening and 22 000 women at re‐screening 3 years later. The response rate was slightly higher at the second screening (74.5 versus 72.1% at the first screening; referral rate, RR 1.11; 95% confidence interval, 95% CI , 1.07–1.14). Compared with the first screening, we observed a significant reduction at the second screening in terms of HPV positivity ( RR 0.55, 95% CI 0.51–0.60), referral rate to colposcopy ( RR 0.47, 95% CI 0.41–0.53), CIN 2+ detection rate ( RR 0.24, 95% CI 0.13–0.39), and positive predictive value ( PPV ) for CIN 2+ at colposcopy ( RR 0.51, 95% CI 0.29–0.87). Conclusions The very low frequency of disease and inadequate PPV at colposcopy indicate that a 3‐year interval after a negative HPV test is too short. Tweetable abstract Three years after a negative HPV the frequency of cervical disease is so low that re‐screening is inefficient.

ObjectiveTo present the results of the first 2 years of a human papillomavirus (HPV) test‐based screening programme outside the research context.DesignPopulation‐based cohort study.SettingA cervical service screening programme in Italy.PopulationWomen aged 25–64 years invited to screening from April 2009 to April 2011.MethodsEligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC‐US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later.Main outcome measuresParticipation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+.ResultsParticipation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25–34 years, 8.2%; 35+ years, 3.6%).ConclusionsCompared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.