Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study

Background: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. Methods: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. Results: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR - 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR - 3.2; 95% CI, 2.0-5.3), and vaginal (HR - 5.5; 95% CI, 2.4-12.3) cancers >= 25 years after CIN3 diagnosis. Conclusion: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. Impact: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. (C) 2016 AACR.