Persistence of high-risk human papillomavirus (HPV) is essential for the development of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN2/3) and has also been associated with non-cervical anogenital cancers including anal, vulvar and vaginal cancer. Thus, CIN2/3 and anogenital cancers share a common aetiology. Still, there is relatively limited knowledge about the long-term risk for non-cervical anogenital cancer in women with a previous diagnosis of CIN2/3.
In a nationwide cohort study, we followed nearly 2.8 million women born in 1918–1990 who were recorded as living in Denmark between 1 January 1978 and 31 December 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, whichever occurred latest, and continued until emigration, death, 31 December 2012 or the date of first diagnosis of anogenital or rectal cancer.
Women with a history of CIN2/3 had higher risks for subsequent anal (HR=3.8; 95% CI:3.2–4.5), vulvar (HR=3.6; 95% CI:3.0–4.3) and vaginal (HR=15.1; 95% CI:11.5–19.9) cancer than women with no such history. After adjustment for smoking and education level, a history of CIN2/3 remained significantly associated with non-cervical anogenital cancer. No excess risk was found for rectal cancer (HR=1.0; 95% CI:0.9–1.2). Analyses in which time since first CIN2/3 was taken into account showed increased relative risks for anal (HR=4.3; 95% CI:3.0–6.1), vulvar (HR=2.9; 95% CI:1.8–4.6) and vaginal (HR=9.7; 95% CI:4.9–19.4) cancers ≥ 25 years after CIN2/3 diagnosis.
Women with a history of CIN2/3 have a long-term increased relative risk for the development of anal, vulvar and vaginal cancer. This finding could inform a decision which may include surveillance for non-cervical anogenital cancers in the follow-up programme offered to women diagnosed with CIN2/3.