The UK National Screening Committee (NSC) based its recommendation that HPV testing should replace cytology in primary screening largely on the 2009 follow-up results of the ARTISTIC trial. The NSC must now decide on screening intervals in time for national roll out of primary HPV screening (due 2019). Options include extending the screening interval up to 10 years for HPV negative women and delaying recall for HPV positive women with normal cytology, as their infections are usually transient.
In the ARTISTIC Trial 24,510 women attending for routine cervical cytology in Greater Manchester in 2001-2003 were recruited. During the trial women were recalled 3-yearly and histology results were obtained from local laboratories. After 2009 histological follow-up and sample collection ended and the women returned to routine cytological screening with recall 3-yearly below age 50 and 5-yearly at age 50-64. We have followed the trial cohort to 2015 through national cancer registration for CIN3 and cancer and through linkage to the cervical screening call-recall system to obtain lifetime cytology records.
The analysis included 24,496 women at round 1 and 13,591 at round 2 (30-48 months later). Follow-up via local histology laboratories and national cancer registration identified 505 cases of CIN3+ (including 22 invasive cervical cancers). The cumulative CIN3+ risk 10 years after a negative HPV test (0.31%, 95%CI 0.18-0.49 in the revealed arm) was similar to that 3 years after negative cytology (0.30%, 95%CI 0.23-0.41 in the concealed arm) and fell sharply with age, from 1.1% below 25 (95%CI 0.7%-1.8%) to 0.08% (95%CI 0.03%-0.20%) above 50.
We found a similar level of protection 10 years after a negative HPV test and 3 years after negative cytology. These data support a much longer screening interval after a negative HPV test than after a negative cytology test.
About three quarters of women with HPV infection and normal cytology clear their infections within about 3 years. Their risk of CIN3+ within this time is low (1.5%), suggesting that the current policy of annual repeat testing and referral after 2 years is too conservative. Approximately 40% of women who remained HPV positive had cleared their initial infection and acquired a new HPV type. Cumulative CIN3+ risks in women with type-specific persistent infections are about 6 times higher than in women with new infections. Triage strategies based on HPV persistence would therefore reduce unnecessary referral of women with new (and largely transient) infections.