221TNF-alpha inhibitor alone (1 case) [ 30 ]. This again echoes the concern for potenti-
ated risk of HTCL with joint anti-TNF and immunomodulator use. Finally, the
occurrence of HSTCL has been noted in patients receiving ant-TNF therapy in the
RA and psoriasis populations, with four and one cases cited by the FDA AERS
study, respectively [ 30 ].
Solid Tumors
Prior literature has also investigated the association between anti-TNF use and solid
organ tumors. A nationwide cohort of 56,146 patients with IBD in Denmark from
1999 to 2012 focused on the 4553 patients who were exposed to anti-TNFs. The
authors found no significant associations between anti-TNF exposure and the devel-
opment of solid tumors, including those of the lip, oral cavity, pharynx, digestive
organs, lungs, breast, and genitourinary system. Additionally, the multivariable rela-
tive risks for most cancers were actually decreased after adjusting for azathioprine
exposure [ 31 ].
The association between anti-TNFs and solid tumors has been studied in the
rheumatology literature. The British Society for Rheumatology Biologics Register,
a national prospective cohort study, evaluated the rates of solid cancer occurrence in
patients with RA receiving anti-TNFs vs. DMARDs. There were 427 solid cancers
reported in 52,549 patient-years in the anti-TNF group and 136 per 11,672 patient-
years in the DMARD cohort. After adjustment for baseline characteristics, there
was no difference in risk of solid cancer for TNF inhibitors vs. DMARDs [ 32 ]. A
review of the RA literature by Lebrec et al. also did not reveal any association
between anti-TNF use and solid tumor development [ 33 ]. In fact, an analysis of the
Corona RA Registry found a decreased risk of solid cancer associated with anti-
TNFs compared to methotrexate [ 34 ].
Cervical Cancer
Various factors have been associated with cervical cancer risk in the general popula-
tion. The most important risk factor is human papilloma virus (HPV) infection.
Other associated risks include immunosuppression (such as human immunodefi-
ciency virus), smoking, age, oral contraceptive use, and exposure to diethylstilbes-
trol (DES). Cervical cancer is relatively rare; the low absolute risk may be associated
with detection and treatment of cervical cancer precursors through screening pro-
grams [ 35 ].
In the IBD population, a population-based Danish cohort demonstrated an
increased risk of cervical dysplasia in both CD and UC patients. The risk of cervical
cancer was increased only in the CD population. It has been theorized that immuno-
suppressive medications can lead to increased cervical dysplasia due to impaired
13 Tumor Necrosis Factor-Alpha Inhibitors and Risks of Malignancy