Human papillomavirus (HPV)-negative women have a very low risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the long term, suggesting that extending the current cervical screening interval to 10 years may be justifiable in women aged 40 and older, researchers reported in BMJ.

Johannes Berkhof, PhD, from the Department of Epidemiology and Biostatistics at the VU University of Medical Center in Amsterdam, the Netherlands, and colleagues conducted a 14-year follow-up of a population-based cohort from the POBASCAM trial. The cervical screening program included 3 rounds of screening occurring every 5 years.

The study included 43,339 women between ages 29 and 61 years with a negative HPV test or a negative cytology test. The participants were randomly assigned to receive HPV and cytology co-testing or cytology testing only.

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The primary outcome of the study was the cumulative incidence of cervical cancer and CIN3+. The investigators also measured reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping, or repeat cytology in women who were HPV positive.

Among HPV-negative women in the intervention group, the incidence of cervical cancer was 0.09% and the incidence of CIN3+ was 0.56%. Women with a negative cytology in the control group had an incidence of 0.09% for cervical cancer and 0.69% for CIN3+.

The risk ratios for cervical cancer and CIN3+ were 0.97 and 0.82, respectively. In addition, the investigators found that, compared with younger women, the CIN3+ incidence was 72.2% lower in women who were HPV negative and older than 40 years of age. However, the researchers observed no significant association between cervical cancer incidence and age.

Among women who were positive for HPV with a negative cytology, HPV 16/18 genotyping, or repeat cytology, CIN3+ incidence was 10.4 times higher than among women who were negative for HPV.

“Our results indicate that primary HPV screening provides better long term protection against cervical cancer than cytology testing,” the study authors wrote. “HPV negative women have a very low risk of CIN3+ in the long term, indicating that extension of the current screening interval in the Netherlands to 10 years seems justifiable. For HPV positive, triage negative women, the long term risk of CIN3+ was too high to support an extension of the screening interval beyond five years for any of the used triage strategies.”


  1. Dijkstra MG, van Zummeren M, Rozendaal L, et al. Safety of extending screening intervals beyond 5 years in cervical screening programs with testing for high risk human papillomavirus: 14 year follow-up of population based randomized cohort in the Netherlands. BMJ. 2016; doi: 10.1136/bmj.i4924.