HPV-positive women with normal cytology remain at increased risk of CIN3 after a negative repeat HPV test

Background:In human papillomavirus (HPV)-based screening, a repeat HPV test is often recommended for HPV-positive women with normal cytology (HPV-pos/cyt-neg), but its absolute risk of cervical precancer (CIN3+) over two screening rounds needs to be assessed.Methods:We compared the 5-year risk of HPV infection and CIN3+ in HPV-pos/cyt-neg women with a negative repeat HPV test to the risk in HPV-negative women with normal cytology (double negatives) in the POBASCAM cohort. We obtained histology data from the Dutch pathology registry (PALGA).Results:Human papillomavirus infection risk was 20.4% (19 of 93) in HPV-pos/cyt-neg, repeat HPV-negative women and 3.2% (294 of 9186; P<0.001) in double negatives. Corresponding CIN3+ risks were 2.0% (4 of 199) and 0.2% (41 of 18 562; P<0.001). Infection risks were also increased in type-specific analyses of HPV16, 31, 33, 39, 52, 56 and 58.Conclusions:HPV-pos/cyt-neg women continue to have an increased CIN3+ risk, also when the repeat HPV test is negative. Therefore, intervals in primary HPV screening should be determined separately for HPV-positive and -negative women.