Trial Information

Characterization of Anal Human Papillomavirus (HPV) Infection in the University of Pittsburgh Inflammatory Bowel Disease (IBD) Cohort Study

Treatment of IBD relies on disease modification by induction of relative immunosuppression
with corticosteroids and latterly and increasingly, by the use of immunomodulators
(azathioprine, mercaptopurine, methotrexate), biological agents such as anti tumor necrosis
factor monoclonal antibodies (infliximab, adalimumab, certolizumab) or with a circulating
receptor fusion protein (etanercept). These agents impair cell mediated immunity (CMI) and
have been associated with increased rates of both tuberculosis and fungal infections in
treated populations beyond that seen with corticosteroids alone. Following initial
infection, HPV is controlled by CMI and manifestations of infection become increasingly
clinically apparent when CMI is impaired due to for example HIV co-infection or systemic
immunosuppression. There is appropriate concern in the IBD treatment community that the use
of immunosuppression to modify disease course may lead to increased rates of HPV associated
disease including warts, dysplasia and ultimately anogenital cancer above and beyond the
established increased risk associated with IBD. In this context it is important to establish
the prevalence of both HPV infection and anal dysplasia in patients with IBD before and
after treatment with a non-steroid immunosuppressive agent. These data will help determine
the need for HPV vaccination and/or anal dysplasia screening in patients with IBD.

VISIT 1 (Screening/Enrollment Visit): This visit will include:

- Medical/medication history.

- Physical exam as per standard of care

- Females of reproductive potential will give a urine sample for a pregnancy test. This
test must be negative.

- An anal Pap test for abnormal cells. The researcher will insert a swab (similar to a
Q-tip) into the anus. The end of the swab will be rubbed against the skin inside the
anus.

- An anal swab to test for HPV (using the same method as the anal Pap)

- Female participants will also have a vaginal swab for HPV. This may be self taken, or
taken by a clinician.

- An exam of the anus and genital area for any lesions or masses.

- A rectal exam with a finger to feel for any abnormalities.

- An anal exam called high resolution anoscopy (HRA) that uses a special microscope and
dyes to examine the anus for abnormal areas. A lubricated plastic speculum will be
inserted into the anus. Then, a swab moistened with acetic acid is placed in the anus
so that abnormal areas will be visible. A colposcope will be used to view the skin
inside the anus. A biopsy, with or without iodine for visualization of the abnormal
areas, may be taken if any lesions have the appearance of high-grade anal dysplasia or
other abnormal findings.

Within 1 day after this visit, study staff will telephone the participant to ask about any
side effects or health problems from the study procedures. If necessary, the participant may
be asked to come to the clinic for a visit.

VISIT 2 (Final Visit): This visit will occur 6 to 12 months after the first visit. Prior to
this visit, participant will be instructed to not have anal sex or insert anything into the
anus, including enemas, for 24 hours before each study visit. This visit will include:

- Medical/medication history

- Physical exam as per standard of care

- Females of reproductive potential will give a urine or 5ml blood sample] for a
pregnancy test. This test must be negative.

- Anal Pap test for abnormal cells

- Anal swab for HPV

- Females participants will also have a vaginal swab for HPV

- An exam of the anus and genital area for any lesions, tenderness or masses

- A rectal exam to feel for any abnormalities

- High-resolution anoscopy (HRA). A biopsy, with or without iodine for visualization of
the abnormal areas, may be taken if any lesions have the appearance of high-grade anal
dysplasia or other abnormal findings.

Within 1 day after this visit, study staff will telephone the participant to ask about any
side effects or health problems from the study procedures. If necessary, the participant may
be asked to come to the clinic for a visit.