Abnormal Anal Cytology and Human Papillomavirus Infection in Women with Genital Dysplasia Ina U. Park MD, MS James Ogilvie, MD Lindsay Darrah, MD Kristin E. Anderson, PhD, MPH Zhong-ze Le, MS Robert Madoff, MD Levi Downs Jr., MD University of Minnesota CDC STD Prevention Conference 2008 Currently can be contacted at the CA Dept of Public Health STD Control Branch

HPV Epidemiology HPV is the most common STD- 80% sexually active people acquire infection by age 50 Prevalence: Estimated 20 million infected Incidence: Estimated 6.2 million infections/yr Cates, W (1999) STD Weinstock, H (2004) Persp Sexual Repro Health

HPV and Anogenital Neoplasia High risk HPV types → cervical cancer and cervical intraepithelial neoplasia (CIN) High risk HPV types also detected in: 92% of Vulvar dysplasia (VIN) 91% of Vaginal dysplasia (VAIN) 89% of Anal dysplasia (AIN) 90% of Anal cancer Cervical intraepithelial neoplasia – CIN, VIN for vulvar, VAIN for vaginal, AIN for anal HPV not necessarily limited to one organ, may ause multifocal infection, dysplasia. There is limited evidence that HPV infection or dysplasia at genital sites may predispose women to infection or dysplasia in the anus. Bosch FX (2002) J Clin Pathol. Hampl M (2006) Obstet Gynecol.

Anal Cancer Incidence in US Women: 2.1 cases per 100,000 Men (all): 2.1 cases per 100,000 Women with genital dysplasia may be at higher risk than general population These women may benefit from anal Pap screening Importance of understanding type distribution of anal HPV. Important b/c of implications for HPV vaccine and its potential for prophylaxis of anal dysplasia/ cancer Daling JR (2004) Cancer Chin-Hong PV, Palefsky JM (2002) CID Hayanga AJ (2006) BMJ

HPV Vaccine and Anogenital Neoplasia Quadrivalent HPV vaccine licensed for prevention of cervical, vaginal, vulvar dysplasia Impact of vaccine on anal HPV infection or anal dysplasia unknown Importance of understanding type distribution of anal HPV. Important b/c of implications for HPV vaccine and its potential for prophylaxis of anal dysplasia/ cancer

AIMS In women with genital dypslasia: AIM 1: Estimate type-specific prevalence of anal HPV infection AIM 2: Estimate prevalence of abnormal anal cytology AIM3: Evaluate risk factors for anal HPV and abnormal cytology

Methods Cross-sectional design Convenience (consecutive) sample of women at 2 university-based colposcopy clinics Recruitment time frame: Apr 06-Mar 07 I have IRB approval to

Inclusion Criteria Age: 18-85 yrs old Biopsy-confirmed diagnoses: Cervical intraepithelial neoplasia II-III Vulvar intraepithelial neoplasia II-III Vaginal intraepithelial neoplasia II-III Cervical, vulvar or vaginal cancer

Exclusion Criteria Current or prior history of anal cancer Prior radiation tx to pelvic region Surgical absence of rectum/anus Received ≥ 1 dose of HPV vaccine

Study Procedures Self-administered, anonymous questionnaire Demographics, medical hx, tobacco use, sexual history (anal sex practices) Anal Cytology Anal HPV Testing/Typing

Approached for consent Subject Diagram Approached for consent N=112 Refused N=8 Enrolled in study N=104 Repeat Biopsy (-) N=2 B/c this was conducted at a referral center, 2 subjects had results from an outside facility with questionable diagnoses or diagnoses 6 months from time of presentation and were were re-colpoed and biopsied---subsequent biopsy showed no evidence of disease Final N=102

Subject Characteristics Mean Age 35.2 (15) Caucasian Race 87% Smoker 46% Immunosuppressive Meds 4% HIV Positive <1% Median #sexual partners 7 (1-100) Age Sexual Debut ≤ 16 years 33% Ever had anal sex Anal sex w/in 3 mos 11%

RESULTS Prevalence of Anal HPV infection 92/102 had sufficient DNA for analysis 45 women (49%) anal HPV negative 47 women (51%) anal HPV positive 34% oncogenic vaccine type (16/18) 13% non-oncogenic vaccine type (6/11) 36% had oncogenic non-vaccine types

RESULTS Prevalence of abnormal cytology 9/102 with abnormal anal cytology 9% (3-14%) 5 ASCUS 2 ASC-H (cannot rule out high grade) 2 LSIL 7/9 women subsequently underwent biopsy and all had low grade anal dysplasia Types associated with ASc-h or lsil? Probably not

RESULTS Risk Factors for Anal HPV % with Anal HPV Odds Ratio (95% CI) Anal Sex Never Ever 45 60 1.0 1.84 (0.79-4.29) Anal Sex (past 3 mos) No Yes 49 64 1.80 (0.49-6.62) History of anal warts 51 75 2.93 (0.29-29.30) We expected these to be correlated with anal HPV infection.

RESULTS Risk Factor Analysis No significant association for either HPV infection or abnormal cytology Age Tobacco use Age sexual debut # partners H/o anal sex H/o Anal warts Risk factors for univariate and multivariate models were selected apriori based on prior literature, mostly conducted in HIV positive MSM

Limitations Generalizability Small sample size Caucasian, insured, University setting Small sample size HPV types at genital sites unknown

Conclusions Women with genital neoplasia also at risk for anal HPV infection High proportion of anal HPV infection includes types covered by current vaccine Abnormal anal cytology relatively rare

Acknowledgments HRSA Faculty Development Grant : 1DHP05168-01-00 Univ of MN Dept of Epidemiology JB Hawley Research Award Univ of MN Department of Ob-Gyn Corrigan Award

Contact Information Ina Park MD,MS Clinical STD Fellow California Department of Public Health STD Control Branch 850 Marina Bay Parkway Building P Richmond, CA 94804 Email: ina.park@cdph.ca.gov

THANK YOU !