Table 1

Secondary trial outcomes

Description of secondary outcomesTime pointAdditional notes
Cross-sectional outcomes for CIN2+ and CIN3+ detection in each armBaseline, following recruitmentAnalyses will be stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
CIN2+ in women randomised to the HPV arm and positive for other oncogenic HPV types (not 16/18)After completion of 12–24 m FUAnalyses will be stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
Cumulative CIN3+ in women randomised to HPV arm who were HPV negative at baseline versus cumulative CIN3+ in those randomised to LBC arm who were LBC negative at baseline using ITT analysisAfter completion of FU at 5 yearsClosed loop testing for non-inferiority and superiority if non-inferiority is declared. Analyses will be adjusted for censoring after CIN2+ treatment or after hysterectomy and stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
Cumulative CIN3+ in women randomised to HPV arm who were HPV negative at baseline versus cumulative CIN3+ in those randomised to LBC arm who were LBC negative at baseline and at 2.5 years. Per-protocol analysis will be performed in women screened and followed up within a defined tolerance period. The strict per-protocol criteria will involve: (1) women randomised to LBC, who had an LBC test in months 27–39 from the date of the original invitation to attend screening (which may be up to 3 months before attendance) and then HPV exit testing at trial exit from 57 to 69 months after recruitment; (2) women randomised to HPV testing, who did not have an intermediate cytology screen until HPV exit testing at 57–69 months (except in the case of the safety monitoring group). Analysis assuming progressively less strict per-protocol adherence criteria will also be performed.After completion of FU at 5 yearsAnalyses will be adjusted for censoring after CIN2+ treatment or after hysterectomy and stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
Cumulative CIN2+ in women randomised to the HPV arm who were HPV negative at baseline versus cumulative CIN2+ in those randomised to the LBC arm who were LBC negative at baseline LBC arm and using intention-to-treat analysisAfter completion of FU at 5 yearsAnalyses will be adjusted for censoring after CIN2+ treatment or after hysterectomy and stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
Cumulative CIN2+ and CIN3+ in women who have an abnormal test result at baselineAfter completion of FU at 5 yearsAnalyses will be adjusted for censoring after CIN2+ treatment or after hysterectomy and stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
Cumulative CIN2+ and CIN3+ in women who were in follow-up management for a previous abnormality at baselineAfter completion of FU at 5 yearsAnalyses will be adjusted for censoring after CIN2+ treatment or after hysterectomy and stratified by recruitment group (DOB <1 July 1980; DOB ≥1 July 1980).
  • CIN, cervical intraepithelial neoplasia; DOB, date of birth; FU, follow-up; HPV, human papillomavirus; ITT, intention to treat; LBC, liquid-based cytology.