July 28, 2010 Cervical Dysplasia in Immune Suppressed Women Jill Gaidos Nancy Hardt Faris Hashim

Background Human papilloma virus (HPV): Causes over 90% of cervical dysplasia. 70% of cervical dysplasia caused by HPV 16 and 18. Progression from dysplasia to cancer is more rapid in immune suppressed patients. HPV vaccine Targets types 16, 18, 6 and 11. Effective in the general population Safe in immune suppressed population.

Background 20 million people currently infected with HPV About half are 15 – 24 years of age. Annually in the U.S., 12,000 women are diagnosed with cervical cancer and 4,000 die. Over $2 billion spent on the treatment of cervical cancer per year in the U.S.

Background Women with lupus: Women with IBD: 10 x increase in cervical dysplasia 20 x with immune suppression Women with IBD: 6 x more likely to develop cervical dysplasia further increased with immunosuppressive medications. Women with renal transplant: All with negative Paps 6 months 18% with HPV+ or cervical dysplasia only 6 months after transplant.

Background American College of Obstetrics and Gynecology recommends annual Pap screening in immune suppressed hosts due to this increased risk, however, prevention, or vaccination, is not currently standard of care.

Study Hypothesis HPV vaccination in immune suppressed patients will decrease the incidence of cervical dysplasia. HVP vaccination is more efficacious if given prior to the initiation of immune suppressive therapy.

Feasibility In a prospective model, this study would be prohibitively expensive, difficult to obtain an adequate sample size, and possibly unethical. We propose to carryout our specific aims using existing data from the Florida State Medicaid administrative database.

Specific Aims Aim 1: Aim 2: Query the Florida Medicaid database to compare the incidence of HPV-related cervical dysplasia in vaccinated and non-vaccinated immune suppressed women. Aim 2: Interrogate the Florida Medicaid database to compare the incidence of cervical dysplasia in patients who received the HPV vaccine prior to receiving immunosuppressive therapy compared to those who received the vaccine after immunosuppressive therapy.

Study Diagram

Approach Medicaid Administrative Database for 2007 – 2009 Data points gender, age/DOB ICD-9, CPT, DRG and pharmacy codes for: Evidence of HPV related disease - pap smear, cervical dysplasia, and HPV vaccination Evidence of immune suppression - immune suppression, transplantation, medication infusions Evidence of risk factors for HPV - pregnancy-related codes, contraception, STD testing/treatment.

Approach Inclusion criteria: Exclusion criteria Females, ages 15 – 26 year olds Immune suppression defined as medications such as prednisone > 2.0 mg/kg/day or 20mg per day for > 2 weeks, anti-TNF agents, cyclosporine, cellcept, prograf, rapamune, etc. Exclusion criteria Males Acute immune suppression, such as treatment with chemotherapy

Innovation Few published studies evaluating the efficacy of HPV vaccination in immune suppressed populations, despite the well documented increased risk. Given the known increased incidence, cost of treatment, morbidity and mortality, determining the efficacy of vaccination is important to change standard of care.

Outcomes We have estimated that the number of immune suppressed patients in this age group in Florida is between 1,000 – 10,000. Given the paucity of published data, even the descriptive data resulting from this analysis are of interest for current practices, health care policy and further research studies.

References www.cdc.gov/cancer/cervical/statistics/index.htm www.cdc.gov/std/hpv/STDFact-HPV-vaccine-hcp.htm Klumb EM, Araujo ML Jr, Jesus GR, et al. Is higher prevalence of cervical intraepithelial neoplasia in women with lupus due to immunosuppression? AraJ Clin Rheumatol. 2010 Jun;16(4):153- 7. Paternoster DM, Cester M, Resente C, et al. Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients. Transplant Proc. 2008 Jul- Aug;40(6):1877-80. Kane S, Khatibi B, Reddy D. Higher incidence of abnormal Pap smears in women with inflammatory bowel disease. Am J Gastroenterol. 2008 Mar;103(3):631-6. Epub 2007 Oct 17.

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