HPV-based cervical screening programmes with a screening interval beyond five years, as currently implemented in the Netherlands, must be evaluated and supported by estimates of the long-term cancer and CIN3 risks.
Fourteen years follow-up data including three consecutive five-yearly screening rounds of a Dutch population-based randomized screening cohort* were collected from women with a negative HPV DNA and/or negative cytology test (n=43,339, aged 29-61 years). At baseline, women were randomly assigned to HPV DNA and cytology co-testing (intervention) or cytology testing only (control) and managed accordingly. In the control group, HPV DNA test results were blinded. Cumulative cancer and pre-cancer (CIN3+) incidences were calculated by Kaplan-Meier methods among HPV DNA negative, cytology negative, and among women with a single or double negative test. In HPV DNA positive, cytology negative women, we examined whether CIN3+ risk could be further reduced by HPV16/18 genotyping and repeat cytology.
The cumulative cancer and CIN3+ incidence among HPV DNA negative women in the intervention group, after three rounds of screening (0.09% and 0.6%) were similar to the corresponding cumulative incidences among women with negative cytology in the control group after two rounds (0.09% and 0.7%). Furthermore, in the intervention group, the CIN3+ incidence rates among HPV DNA positive women with negative triage were substantially higher than the CIN3+ incidence among HPV DNA negative women (rate ratios 10.4 to 29.1).
The long-term CIN3+ and cancer risks among HPV DNA negative women are low and are supportive of an extension of the screening interval. HPV DNA positive, triage-test negative women have a non-negligible long-term CIN3+ risk and should therefore be rescreened within five years. HPV-based programmes with long intervals can therefore only be implemented in conjunction with risk-stratification.
* the POBASCAM trial, trial registration: ISRCTN20781131