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 to 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 and were negative and had at least one post-FOCAL cervix screen were included (N = 5537). 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 seven years or later. Average incidence rates of CIN2+/CIN3+ lesions over follow-up were 0.50 (95% CI: 0.31, 0.78) and 0.18 (0.07, 0.36) per 1000 person-years, respectively. Hazards were higher for younger ages (non-significant trend). Conclusions:Among women with a single negative HPV test, long-term risk of CIN2+ detection was low, particularly through seven 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 five-year or longer intervals.