Title: Long-term follow-up of ARTISTIC cervical screening trial cohort
Funder: Department of Health (England)

Abstract: In the ARTISTIC Trial 24510 women undergoing routine screening by liquid-based cytology were also tested for HPV (Hybrid Capture 2 with HPV typing if positive) and randomised for the HPV result to be concealed or revealed. Women were followed up until 2009 (6-8 years after entry) via two cytology laboratories in the Manchester area. Any women moving out of the area were lost and these laboratories have now been restructured to cover a different geographical area. We shall extend follow-up of the ARTISTIC Trial cohort until December 2015 (up to 14 years from entry) through the NHS Central Register (cancer incidence and mortality) and the Open Exeter national screening programme database (cervical screening records) and review all histopathology reports for CIN3 and cervical cancer held by cancer registries. The Open Exeter database includes all cervical screening records regardless of the Health Authority in which the woman resides. The introduction of primary HPV testing in the NHS cervical screening programme will require several practical decisions on test method and frequency with large effects on costs staff time and patient acceptability as well as on effectiveness of cancer prevention. 1. The role of HPV typing. HPV typing provided by different tests ranges from none (HC2) to partial (COBAS) or full typing (several systems). Possible follow-up policies include immediate referral of HPV16/18 and delayed retesting for other types immediate cytology of all HPV positives and a delay of at least a year before retesting then treating all women with type-specific persistence. 2. Age at first HPV test. NHS CSP sentinel sites will implement HPV testing beginning at age 30 when most infections acquired before age 25 will have disappeared. Starting screening as early as age 22 could be cost-effective if HPV positive results were followed up (say) 3 years later without intervention. At the next screening round at age 25 women with type-specific HPV persistence over 3 years would be treated and new infections would be followed up 3 years later.3. Test specificity. If a quantitative test such as HC2 is used the conventional cutoff (RLU = 1) gives a false positive rate of about 2% which in older women is about a third of all positive results. We shall analyse age-specific effects of different cutoffs. 4. Age at last HPV test and test sensitivity. An attractive cost-saving possibility is to stop screening at age 50 in women who are HPV negative. A final HPV test at age 50 might require a more sensitive test than at younger ages. Two women in the ARTISTIC trial have already developed invasive cervical cancer after a negative HC2 sample that was HPV16 positive when retested by PCR. ARTISTIC over-recruited older women and 43% of women in the trial will be aged over 55 years by 2015.5. Screening interval. The screening interval after a negative test can be much longer with HPV testing than with cytology. Long-term data are limited but the cancer risk may be negligible up to 10 years after a negative test. Extending follow-up to 2015 will increase the median follow-up from 7 to 13 years from entry and from 4 to 10 years from round 2 providing a basis for evaluating policies in relation to HPV clearance acquisition and persistence. For the purpose of modelling an established programme using HPV screening an important group are women who were negative at their previous test. This analysis must begin at the 2nd screening round when these women can be identified.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS;INFECTION