PhD Dissertation (2020)
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic autoimmune disease. In 2016, more than 3.1 million persons were affected by the condition in the United States (US). IBD has a relatively low mortality rate, but it is associated with a high risk of complications, such as malnutrition, fistula, bowel obstruction/perforation, and increased risk of colon cancer. Furthermore, medical therapies for IBD are expensive and lead to a high economic burden on the healthcare system. Medical therapies, such as immunosuppressants and anti-tumor necrosis factor (TNF) that are used as a standard of care in IBD, cause numerous serious side effects, including opportunistic infection from immunosuppressed status and bone marrow suppression. As a result, IBD patients are at elevated risk of infectious diseases, and the evidence suggests that Human Papillomavirus (HPV) infection may be one of them. Also, data suggests that IBD patients may have persistent HPV infection attributable to chronic systemic inflammation, immunosuppression from treatment, or both. The impact of the systemic symptoms and the therapies on the risk of all the HPV-associated cancers (cervical, anal, oropharyngeal, vulvar, vaginal, penile cancer) among IBD patients has not been well described, especially among IBD patients in the US. Given the high expenditures associated with IBD treatments and cancer treatments, and given the poor health-related quality of life, studying the association between IBD and HPV-associated cancers and its clinical and economic impact is important for developing adequate prevention guidelines and improving the quality of life of the IBD patients.
Using Optum® private insurance claims database and HCUP National Inpatient Sample database, we examined if IBD diagnosis is associated with increased risk for HPV-associated cancers (Aim 1) and higher concurrent HPVAC-associated cancer diagnosis (Aim 2). Also, we assessed the clinical outcomes of HPV-associated cancers in IBD patients (IBD-HPVAC) compared to HPV-associated cancers in patients without IBD (non-IBD-HPVAC), such as post-procedural complications, non-routine discharges, and length-of-stay (LOS) among HPVAC-related admissions, using NIS data. To estimate the economic burden of IBD-HPVAC, we calculated inpatient costs among IBD-HPVAC admissions compared to non-IBD-HPVAC admissions (Aim 3).
In Aim 1, we found that IBD patients were at higher risk for anal cancer compared to RA patients. However, the risk in IBD patients when compared to diverticulitis patients was inconsistent, depending on the analysis models and sex of the patients. The results show a possibly stronger association between the disease location and the anal cancer risk. On the other hand, we did not see statistical differences in other types of HPVAC. Some of the cancers showed elevated risk trends in IBD patients, but the results were not statistically significant. In Aim 2, we found that IBD was strongly associated with anal cancer compared to either RA or diverticulitis in both men and women. The likelihood was especially higher when compared to RA than diverticulitis in men, which indicates a stronger association of the location of the disease with anal cancer in men. On the other hand, the association of the other cancer types seemed to be stronger with autoimmune disease status. Especially in oropharyngeal cancer, the likelihood of oropharyngeal cancer in IBD patients was significantly reduced compared to RA patients but significantly increased compared to diverticulitis patients. Our analyses in Aim 3 found that IBD status was significantly associated with the clinical outcomes of anal cancer, showing the strong clinical association between IBD and anal cancer. Meanwhile, except for LOS and inpatient costs in vaginal cancer admission, other HPVAC did not show a significant association with IBD in their clinical or economic outcomes. This finding weighs more on the crucial role of the disease’s location of IBD in cancer risk and burden.
Taken altogether, the data presented here provide evidence that the location of the disease in IBD was significantly associated with the risk and burden of anal cancer. While there were inconsistent findings among other types of HPVAC, our study results consistently pointed to the strong clinical association between IBD and anal cancer. Future studies, therefore, will have to concentrate on the association between IBD and anal cancer, especially in anal cancer prevention among IBD patients.