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ability clear human papilloma virus (HPV) infections [ 36 ]. Kane et al. conducted a
case-control study evaluating 40 patients with IBD and their incidence of abnormal
pap smears as compared to the control population. Patients with IBD did have a
higher risk of an abnormal pap smear as compared to healthy controls. In addition,
patients with a history of immunomodulator use were more likely to have an abnor-
mal pap smear associated with high risk strains of HPV (serotype 16 or 18) [ 37 ].
However, the outcome of this study was abnormal pap rather than cervical dysplasia
or cancer.
Singh et al. evaluated data from the University of Manitoba IBD Epidemiology
Database, matching 19,692 women with cervical cytologic or histologic abnormali-
ties on pap smear with 57,898 controls with normal pap smears [ 38 ]. While there
was no associated risk for abnormal pap smears in patients with UC and CD who
had not been prescribed ten or more prescriptions of oral contraceptives, there was
an increased risk associated with concomitant corticosteroid and immunosuppres-
sant use. The immunosuppressant medications used among patients in this study
were azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, or infliximab.
Interestingly, the increased risk was not present with either corticosteroid or immu-
nosuppressant use alone [ 38 ]. While there have been conflicting reports about the
baseline risk of abnormal cervical dysplasia and cancer in IBD patients, there does
appear to be an association with increased immunosuppression use in this popula-
tion. The limited available data cannot distinguish risks by specific classes of
medications.
Colorectal Cancer
It is well established that patients with extensive, long-standing colitis have a higher
risk of colorectal cancer (CRC) than the general population [ 39 ]. The risk of CRC
in patients with UC fluctuates between 0.9–8.8-fold and 0.8–23-fold in patients
with pancolitis [ 40 ]. There is no statistically increased risk of CRC in CD [ 41 ].
However, in patients with long-standing Crohn’s colitis, the risk becomes similar to
that of UC [ 42 ]. TNF-alpha has been identified as a crucial mediator in the develop-
ment of CRC in IBD. This implies TNF-alpha inhibition may play a role in cancer
reduction [ 40 ].
Data have shown that CRC risk is linked to the actual histologic inflammatory
activity over time. Thus, various medications have been studied that have reduced
the risk of CRC and/or dysplasia. A case-control study by Ruben et al. of 141
patients with UC without CRC and 59 matched patients with UC who developed
CRC demonstrated an increased risk of CRC with inflammation, as well as a
decreased risk of CRC with the use of immunomodulators such as azathioprine,
6-MP, and methotrexate [ 43 ]. Classes of medications that have been associated with
reduced risk include 5-amino salicylic acid (5-ASA) agents [ 44 ] and immunomodu-
lators such as thiopurines [ 45 ]. It is also possible that anti-TNF medications simi-
larly reduce this risk through inflammation reduction.
J.T. Hughes and M.D. Long