HPV testing is better than cytology in primary screening because it reduces subsequent cancer incidence. Moreover, the long-term CIN3+ risk is lower after a negative HPV test than after normal cytology, justifying a longer screening interval in older women who are less likely to become infected. The main concern with a screening interval of up to 10 years in HPV negative women aged over 40 is their invasive cancer risk, which is about 1 in 1,000 over 10 years.
In the ARTISTIC Trial 24,510 women attending for routine cervical screening in 2001-2003 had cytology and HPV testing at entry and 3-yearly until 2009. We have followed the cohort to 2015 through national cancer and CIN3 registration.
Respective numbers of CIN3s and cervical cancers by age at diagnosis were 208 and none aged 20-29, 192 and 7 aged 30-39, and 83 and 15 aged 40-65. Six of the 22 women with cancer were HPV negative by HC2 at entry, but on retesting their stored entry samples by PCR 5 were HR-HPV positive. 2 of these 6 cancers were diagnosed within 5 years of the negative HC2 test and were probably present at entry. At entry one was cytologically abnormal and both had HPV16 detectable by PCR.
The important measure of efficacy with a long screening interval is the cancer risk, not the CIN3 risk. Most cancers caused by subsequent HPV infection will develop towards the end of the interval due to the lag from infection and CIN3 development to malignancy. These are likely to be diagnosed at an early stage even with a 10-year interval. However, cancers present at the time of the negative HPV test would be at high risk of being advanced or metastatic 10 years later. The results of ARTISTIC and other large studies suggest that most of these prevalent cancers would be detected by more sensitive HPV testing and/or cytology co-testing, but the numbers are small even in very large studies. Collaborative analyses focussed on this issue are needed to provide evidence on the effects on early and advanced cancer incidence of enhanced testing procedures with screening intervals of up to 10 years at different ages, and particularly at a woman’s final HPV test. Modern HPV tests may already be sensitive enough to prevent most of the small but serious hazard of undetected invasive cancer.