FC 11-034 - YEAR EXIT RESULTS FOR WOMEN WITH NO CIN2 OR WORSE DETECTED IN EARLIER SCREENING ROUNDS IN THE HPV FOCAL TRIAL

09. HPV screening
A. Coldman 1, L. Smith 2, L. Gondara 2, D. Van Niekirk 2, K. Ceballos 2, M. Krajden 3, D. Cook 3, D. Quinlan 4, M. Lee 4, G. Stuart 4, R. Martin 4, S. Peacock 1, L. Gentile 2, G. Ogilvie 4.
1BC Cancer Research Centre (Canada), 2BC Cancer Agency (Canada), 3BC Centre for Disease Control (Canada), 4University of British Columbia (Canada)

Background / Objectives

The HPV FOCAL RCT compares liquid based cytology (LBC) with hybrid capture 2® (HC2) triage of ASCUS at entry and 2-years (Control Arm) to HC2 testing with LBC triage at entry (Intervention Arm).  Women exit with HC2/LBC co-testing performed at four years in both arms. We examine exit results in subjects without cervical intraepithelial neoplasia or worse (CIN2+) detected in earlier trial screening.


Methods

Subjects were included if they were eligible for routine screening at the time of the exit screen. For the Intervention arm this was women HC2 Negative at baseline (HPVBaseNeg), or HC2 positive and negative for intraepithelial lesion or malignancy (NILM) at baseline and HC2 negative at 6-12 months retesting (HPVRev), or recommended for colposcopy where no CIN2+ was detected (HPVColpoNeg). For the Control arm this was women NILM or atypical cells of undetermined significance (ASCUS) and HC2 negative at baseline and at two years (CYTNeg), recommended for colposcopy at baseline and no CIN2+ found (CYTColpoNeg0) or recommended for colposcopy at 2-years, but not at baseline, and co CIN2+ found (CYTColpoNeg2).  Results presented are based upon exit (4-year) co-testing where women were referred to colposcopy if HC2 positive or ASCUS or worse. 


Results

9,552 women were randomized to the Intervention arm and 8,338 were eligible and attended the exit screen, 9,457 women were randomized to the Control arm and 7,424 were eligible and attended the exit screen: the breakdown of subjects is given in the attached table. The overall relative risk of CIN2+ at exit for Intervention versus Control was RR=0.86 (95%CI=0.58-1.26). For those with a single negative HPV tests versus those with two consecutive negative LBC tests (i.e. HPVBaseNeg versus CYTNeg) the relative rate at exit contesting was RR=0.69 (0.45-1.07). Women having earlier negative colposcopy were at elevated risk in both arms compared to others eligible for routine exit screening: Intervention Arm RR=10.0 (5.5-18.3); Control Arm RR=5.0 (2.1-11.5).

Table: Rates of CIN2+ Identified at 48 Month Exit Cotesting by Study Arm Subgroup
  HPVBaseNeg HPVRev  HPVColpoNeg CYTNeg  CYTColpoNeg0 CYTColpoNeg2
Number 7869 166 303 7308 108 80
CIN2+ 35 2 14 47 5 1

Rate/100

(95%CI)

0.44

(0.32-0.61)

1.2

(0.33-4.3)

4.6

(2.8-7.6)

0.64

(0.48-0.75)

4.6

(2.0-10.4)

1.3

(0.2-6.8)

 


Conclusion

 

Women recommended for colposcopy with no significant lesion detected were at elevated subsequent risk and their careful surveillance is indicated.


References

Ogilvie, G et al,  HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV-based primary screening to liquir-based cytology for cervical cancer, IJC 140 (2017):440-448