Human papillomavirus (HPV) testing is being considered as the primary screening test for cervical cancer in England, rather than the currently used cytology test. We aimed to estimate the impact of primary HPV testing on incidence and morbidity of cervical cancer in England by estimating the proportion of cervical cancer diagnosed within 6 years of a negative cytology. We used a population-based case-control study of prospectively recorded data on cervical screening in England between 1988 and 2012, including 8774 women with invasive cervical cancer aged 25 to 64 and 17,341 controls. We used incidence rates in 2010 to estimate absolute risks. We found that 38.8% of all women with cervical cancer had a negative test within 6 years of diagnosis. Assuming HPV testing is 95% sensitive for cancers that would develop over the next 6 years but were missed by cytology, and that 4.3% of those diagnosed by cytology would be missed by HPV testing, we estimate that a maximum of 32.6% of current cases in women invited for screening aged 25 to 64 could be prevented. This translates to a reduction in the rate of cervical cancer in this age group of 4.2 per 100,000 women per year in England, equivalent to 587 cancers.