The relative risk of noncervical high‐risk human papillomavirus‐related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3: A population‐based study

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long‐lasting increased risk for noncervical high‐risk human papillomavirus (hrHPV)‐related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post‐treatment. Cases of noncervical hrHPV‐related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person‐years of follow‐up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV‐related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow‐up and prophylactic hrHPV vaccination are warranted.