Assessing 10-Year Safety of a Single Negative HPV Test for Cervical Cancer Screening: Evidence from FOCAL-DECADE Cohort

Abstract

Background: Long-term safety of a single negative human papillomavirus (HPV) test for cervical cancer screening is unclear. The HPV FOr cerviCAL Cancer Trial (FOCAL) was a randomized trial comparing HPV testing with cytology. The FOCAL-DECADE cohort tracked women who received one HPV test during FOCAL, and were HPV negative, for up to 10 years to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) detected through a provincial screening program.

Methods: FOCAL participants who received one HPV test, were negative, and had at least one post-FOCAL cervix screen were included (N = 5,537). We constructed cumulative incidence curves of CIN2+/CIN3+ detection, analyzed cumulative risk of detection at intervals post-HPV test, calculated average incidence rates for detection, and compared hazard across ages.

Results: Ten years after one negative HPV test, the probability of CIN2+ detection was lower than 1%, with most lesions detected 7 years or later. Average incidence rates of CIN2+/CIN3+ lesions over follow-up were 0.50 [95% confidence interval (CI), 0.31-0.78] and 0.18 (95% CI, 0.07-0.36) per 1,000 person-years, respectively. Hazards were higher for younger ages (nonsignificant trend).

Conclusions: Among women with a single negative HPV test, long-term risk of CIN2+ detection was low, particularly through 7 years of follow-up; thus, one negative HPV test appears to confer long-term protection from precancerous lesions. Even 10-year risk is sufficiently low to support extended testing intervals in average-risk populations.

Impact: Our findings support the safety of screening policies using HPV testing alone at 5-year or longer intervals.

Figure 1.

A diagram of FOCAL and FOCAL-DECADE by baseline HPV result. All women enrolled in the safety arm of the FOCAL randomized control trial were given HPV testing at baseline. All participants who (1) remained eligible for FOCAL during the entire trial (N = 10 excluded), (2) were HPV negative at baseline (N = 519 excluded), and (3) had at least one screen post baseline (N = 148 excluded) were included in this analysis (N = 5537). HPV = high risk human papillomavirus; LBC = liquid-based cytology; Provincial screening = BC Cancer Cervix Screening Program recommends conventional Pap screening given by individual healthcare providers ever 24–36 months* * In June 2016, the BC Cancer Cervix Screening program changed the recommended cervix screening interval from 24 months to 24–36 months for average risk individuals.

Figure 2.

Cumulative incidence of CIN2+ detection over follow-up. (A) includes the overall population, (B) stratifies by 10-year age group, and (C) by binary age groups. Note that, for clarity, y-axes differ for each plot. Women are censored at either CIN2+ detection date or their most recent screening date, with all remaining women censored at 10 years. Table 2 shows cumulative events and total number at risk at 2-year intervals post-baseline entry into FOCAL.