1. 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

2. 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

3. 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.

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

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

11. 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

12. 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%

13. 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

15. 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

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

17. 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

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

19. 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

20. 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

21. 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

22. THANK YOU !