Fast track — ArticlesRisk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study
Introduction
Women with a history of a cervical intraepithelial neoplasia (CIN) are well known to be at increased risk of vaginal, vulvar, and anal cancer,1, 2, 3, 4, 5 presumably due to human papillomavirus (HPV) infection. Specifically, HPV infection has been associated with anal cancer, non-keratinising vulvar cancer,6, 7, 8, 9, 10 and to some extent with vaginal cancer.11 The risks of developing these cancers associated with HPV infection is lower than that reported for grade 3 CINs, or for invasive cervical cancer.12 However, the extent of these associations remains poorly characterised.
Although the incidence of anal and vulvar cancer is rapidly increasing,13, 14, 15 cancers of the vagina, vulva, and anus are still rare.14, 15, 16 In certain subpopulations, such as among men who have sex with men, anal cancer is comparably common.17, 18, 19 The first vaccine against HPV-related disease is now available.20, 21, 22 Although this vaccine, and another soon to be released, have been developed and tested to prevent CIN and invasive cervical cancer, they are also expected to prevent other anogenital cancers and genital condylomas.20 Results from clinical trials of HPV vaccination have been extremely encouraging.20, 21, 22, 23
Almost 100% of tissue samples from grade 3 CINs are infected with HPV.24 Therefore, estimation of the risk of anogenital cancer after diagnosis of grade 3 CIN could potentially further our understanding of the relation between HPV infection and anogenital cancer. Since such data can be used to predict the potential effect of HPV vaccines, which is essential for the planning of health care and vaccination programmes, we did a population-based cohort study to assess the risks of vaginal, vulvar, anal, and rectal cancer in women with a history of a grade 3 CIN diagnosis.
Section snippets
Participants and procedures
Since 1947, all residents of Sweden have been assigned a unique national registration number. This number is routinely used in everyday life, in contact with authorities and health-care providers, and as a unique personal identifier in national population and health databases. From the Swedish National Population Register, we extracted the national registration number, date of birth, and date of death for all women who were born between 1918 and 1986 (ie, aged 18–50 years at some point during
Results
From the register of the Swedish population, we identified 3 747 698 women who were eligible for analysis. The women were on average quite young; almost 50% of the risk time included in the study was contributed by women aged less than 40 years. Risk time was relatively evenly distributed across the study period, with a slight excess in the later decades. The study population is described in more detail in table 1. During a median follow-up of 27 years (range 0–37 years), 91 229 349
Discussion
In this large population-based cohort study in more than 3·7 million women over a period of 37 years, we have shown a strong and consistent association between a history of grade 3 CIN and cancers of the vagina, vulva, and anus. The IRRs of these three cancers were substantially increased for more than 10 years after the first recorded cervical lesion. As was expected, we have found no evidence of such an association with cancer of the rectum.
Since HPV infection is present in almost all
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