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

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.