From the AGA Journals

Study found two-way link between IBD and cervical cancer

Key clinical point: Inflammatory bowel disease – particularly Crohn’s disease – might increase risk of cervical cancer.

Major finding: Women with Crohn’s disease had an estimated 53% increase in risk of developing cervical cancer, compared with controls.

Data source: Population-based cohort study of 27,408 women with inflammatory bowel disease and 1,508,334 controls.

Disclosures: The study was funded in part by the Danish Council of Independent Research. The investigators reported having no relevant financial disclosures.

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Cancer risk elevated among women with IBD

The possibility that intraepithelial neoplasia or dysplasia of the uterine cervix might occur more frequently in women with inflammatory bowel disease (IBD) was raised almost 10 years ago. It stands to reason that some women with Crohn's disease or ulcerative colitis might be at increased risk of cervical dysplasia - after all, the primary driver of cervical neoplasia is infection with human papillomavirus, many patients with IBD are on drugs that suppress the immune system, and other immunosuppressive states (for example, HIV infection, post organ transplant) have been associated with higher rates of cervical dysplasia and cancer. However, the results of studies on this question have been conflicting.

These researchers from the Statens Serum Institut in Copenhagen have harnessed the power of the nationwide Danish medical informatics system to answer many epidemiologic questions about various aspects of IBD. The researchers identified a cohort of more than 18,000 women with ulcerative colitis, more than 8,000 women with Crohn's, and more than 1.5 million women with neither, and "followed" them through a pathology registry for cervical dysplasia and through a cancer registry for cervical cancer. Access to a prescription registry allowed stratification of risk based on medication use. Careful review of the methods section of the paper suggests that this study was well designed and executed.

Women with ulcerative colitis were about 15% more likely than controls to develop dysplasia, but the cancer risk was not increased. Women with Crohn's disease were about 25% more likely to develop dysplasia relative to controls and more than 50% more likely to develop cervical cancer. There were no significant differences in neoplasia risk when stratified by medication use, although there were trends toward increased risk of high-grade cervical dysplasia in women with Crohn's disease who were prescribed azathioprine or anti-tumor necrosis factor agents. Interestingly, the risk of cervical neoplasia was elevated in women well before the diagnosis of IBD.

The study confirms that there is an elevated risk of cervical dysplasia and cancer among women with IBD, and that the risk seems slightly higher in those with Crohn's disease. The finding of the increased risk of neoplasia well before the diagnosis of IBD suggests that perhaps a relative state of immunosuppression exists in patients who are ultimately diagnosed with IBD. In some respects, I found this to be the most intriguing aspect of the paper, and it needs to be explored further in both prospective and retrospective studies.

Dr. Edward V. Loftus Jr., AGAF is professor of medicine and director of the inflammatory bowel disease interest group, division of gastroenterology and hepatology, at the Mayo Clinic, Rochester, Minn. He has consulted for and received research support from UCB, AbbVie, and Janssen.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

References

Women with Crohn’s disease had about a 53% greater risk of developing cervical cancer compared with controls, and women with inflammatory bowel disease had a significantly greater risk of having had cervical neoplasia years earlier, according to a large population-based study reported in the April issue of Clinical Gastroenterology and Hepatology (http://dx.doi.org/10.1016/j.cgh.2014.07.036).

“We found a two-way association between inflammatory bowel disease, notably Crohn’s disease, and neoplastic lesions of the uterine cervix. This observation is not explained by differences in screening activity,” said Dr. Christine Rungoe at Statens Serum Institut in Copenhagen and her associates. “Patients with IBD should be encouraged to follow the screening program for cervical neoplasia, and clinicians should be aware of the slightly increased risk of HPV-related cervical lesions in IBD patients.”

Studies of IBD and cervical neoplasia have yielded mixed results as to a possible association. Some experts have postulated that underlying immunologic changes or the use of immunosuppressive drugs in IBD could thwart patients’ ability to clear HPV infections, thereby increasing their risk of developing cervical neoplasia. To explore that possibility, Dr. Rungoe and her associates compared rates of cervical dysplasia or cervical cancer among 27,408 women newly diagnosed with ulcerative colitis or Crohn’s disease and 1,508,334 controls without IBD. They identified cases and controls from a national patient registry of about 4 million women living in Denmark during 1979-2011. They also calculated the likelihood of a cervical neoplasia diagnosis preceding IBD.


Source: American Gastroenterological Association

Women with Crohn’s disease had a 26% higher rate of low-grade intraepithelial lesions of the cervix, a 28% greater incidence of high-grade lesions, and a 53% greater risk of cervical cancer compared with controls, the researchers reported (incidence rate ratios and 95% confidence intervals, respectively: 1.26, 1.07-1.48; 1.28, 1.13-1.45; and 1.53, 1.04-2.27). Women with ulcerative colitis also had about a 12%-15% increase in risk of developing cervical dysplasia, compared with controls (IRR for low-grade lesions, 1.15; 95% CI, 1.00-1.32; IRR for high-grade lesions, 1.12; 95% CI, 1.01-1.25), but no significant increase in cervical cancer risk.

Notably, women newly diagnosed with IBD had a “markedly elevated” odds of having been diagnosed with cervical neoplasia up to 10 years beforehand, the investigators reported. “This is a novel finding that may suggest a yet unexplored common susceptibility to IBD and cervical neoplasia, rather than an etiologic role of IBD or its treatment in development of cervical neoplasia,” they said.

Treatment with common IBD therapies such as azathioprine, mesalamine, and corticosteroids did not affect rates of cervical neoplasia, but women with Crohn’s disease who had used tumor necrosis factor–alpha antagonists had an 85% increase in high-grade intraepithelial cervical lesions. They also had a 2% increase in risk of these lesions for each filled prescription for hormonal contraceptives.

The frequency of cervical screening was slightly higher among women with ulcerative colitis, compared with controls, but was similar between controls and women with Crohn’s disease, the investigators noted.

The study was funded in part by the Danish Council of Independent Research. The investigators reported having no relevant financial disclosures.

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