Anal Human Papillomavirus in Inflammatory Bowel Disease Study
Condition: Inflammatory Bowel Disease (IBD); Ulcerative Colitis (UC); Crohn's Disease (CD); Anal Human Papillomavirus
MeSH terms: Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases
Study type: Observational

Summary: 
      This is an observational cohort study with two time points (baseline and after at least 6
      months of treatment with a non-corticosteroid immunosuppressive agent for inflammatory bowel
      disease (IBD)). Approximately 40 participants, both male and female, 18 years of age and
      older will be recruited from the Pittsburgh IBD Cohort.

      Participants will have a histological diagnosis of IBD (Ulcerative Colitis (UC) or Crohn's
      Disease (CD)) and will be attending for colonoscopy prior to starting a non-corticosteroid
      immunosuppressive agent as part of standard medical care. Immediately following the
      colonoscopy, an anal exam will be performed for research purposes to include:

        1. Perianal inspection

        2. Anal canal HPV swab

        3. Anal cytology

        4. Digital anal examination

        5. High resolution anoscopy (HRA) and biopsy of all lesions with visual criteria consistent
           with high-grade anal dysplasia

        6. For female participants a self- or clinician-taken vaginal swab for HPV typing.

      These procedures will be repeated at routine colonoscopy following at least 6 months but
      within 12 months of non-corticosteroid immunosuppressive treatment.
    

Detailed description: 
      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.
    

Intervention name(s): Venous blood samples, anal swab samples, vaginal swab samples, high resolution anoscopy (HRA), anal biopsy samples
Intervention type(s): Procedure
Intervention description(s): Before and at least 6 months after starting a new non-steroid immunosuppressive agent for IBD treatment, eligible participants who are attending for routine colonoscopy will have:
Anal swab samples (and vaginal swab samples for female participants) for human papillomavirus PCR typing (6, 11, 16, 18, 31, 33, 45, 52, 58)
High-resolution anoscopy and biopsy of all visible high-grade dysplastic lesions based on validated colposcopic criteria
Anal cytology testing
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Men and women 18 years + with a histological diagnosis of IBD (ulcerative colitis or
        Crohn's disease) who are undergoing a colonoscopy prior to starting a non-corticosteroid
        immunosuppressive agent
      
Biospecimen description: 
      Venous blood, anal swabs, vaginal swabs, high resolution anoscopy (HRA), anal biopsy samples
    
Keywords: Non-corticosteroid immunosuppressive agent