Women’s Health Update

1. Women’s Health Update Alexandra Hall MD amh89@cornell.edu Beth Kutler FNP bk82@cornell.edu Cornell University

2. Understanding the Data • The New Pap Smear Guidelines • The New Medical Eligibility Criteria • for Contraceptive Use • Update on STI Treatment and Diagnosis • What’s New in Emergency Contraception

3. Understanding …. and Explaining the Data

4. Explaining Risk • Absolute Risk • Attributable Risk • Relative Risk

5. Absolute Risk The percentage of people in a group who experience a discrete event Number of events experienced Total exposure time of people at risk

6. Example of Absolute Risk The “pill scare” of 1995… • Of 100,000 women using third generation progestins (desogestrel, norgestimate), 30 people developed a VTE (venous thromboembolic event) per year • Absolute Risk = 30 per 100,000 women years (.03 %)

7. Attributable Risk • The difference in risk between those exposed and those not exposed • Reflects extra risk associated with exposure Risk in exposed – Risk in unexposed

8. Example of Attributable Risk • The absolute risk of VTE in women who took second generation OCs (norgestrel, levonorgestrel) was 15 per 100,000 woman years compared with 30 per 100,00 woman-years in those using third generation OCs. • The attributable risk of VTE in women taking third generation OCs is 15 per 100,000 • 30/100,000 - 15/100,000= 15/100,000 (.015%)

9. Relative Risk • Frequency of the outcome in the exposed group divided by the frequency of the outcome in the unexposed group. • Reflects the likelihood of developing an outcome based on an exposure

10. Relative Risk Example (30/100,000) (15 / 100,000) Absolute risk of taking third generation OCs Absolute risk of taking second generation OCs = 2

11. Interpreting RR Relative RiskInterpretation 1.0 No increasein risk of outcome in exposed group compared with unexposed group >1.0 Increased risk of outcome in exposed group <1.0 Decreased risk of outcome in exposed group Women taking 3rd generation OCs had a risk of VTE two times that of women taking second-generation OCs.

12. Confidence Interval • Confidence Intervals are a way of taking data from a sample and saying something about the population from which the sample was drawn. • If the value 1.0 is in the range of the confidence interval, it can be concluded that the data is not statistically significant

13. Odds Ratio • Quantifies risk for case-control studies in the same way that relative risk quantifies risk for cohort studies • Frequently seen in medical studies

15. Pap Guidelines What was ACOG thinking?!

16. Pap Screening for Cervical Cancer • Is Effective (1) • Cervical CA incidence has declined more than 50% since 1975 due to the introduction of pap screening programs • 1975: 14.9 per 100,000 women • 2006: 6.5 per 100,000 women • Mortality rates have similarly declined • But only if you do it (2) • 50% of those women diagnosed with cervical cancer have never been screened • Another 10% have not had a Pap within the past 5 years before diagnosis • 25% of cancer cases are in women over age 65 (30% of women over age 60 report no pap in past 3 years) • Uninsured, ethnic minorities (particularly Hispanic and Black Americans) and poor women (esp rural) are also disproportionately underscreened (1) http://seer.cancer.gov.csr.1975_2006 (2) http://consensus.nih.gov/1996/1996CervicalCancer102PDF.pdf)

19. Start screening at age 21, regardless of coitarche

20. Adolescents have a very high rate of HPV infection • Ho GY et al 1998 NEJM • 608 women at New Brunswick State, NJ • 6 month intervals for 3 years • Cumulative incidence of HPV was 43% • Woodman et al Lancet 2001 • 1075 women aged 15-19, initially HPV neg • 6 month intervals for 3 years • Cumulative incidence of HPV was 44%

21. Adolescents have a very high rate of HPV infection • Brown et al, J Infectious Dis 2005 • 60 adolescents aged 14-17, inner city, 85% Afr. Am. • Q3 month exam + swab, weekly self-swab x 2 years • Cumulative prevalence 82% • Winer et al, Am J Epidemiol 2003 • 603 college students in Washington State over 10 years • Q4 month visits for 4 years for most women • 24-month cumulative incidence was 32% • 60-month cumulative incidence was 60%

22. Cumulative HPV incidence among sexually active women who were HPV negative at enrollment

23. Shouldn’t we be worried? NOpe

24. Most adolescents will clear HPV spontaneously • Ho GY et al 1998 NEJM (college in NJ) • Median duration of infection was 8 months • Moscicki et al J Pediatrics 1998 • 618 young women positive for HPV, Q 4 month pap, colpo, HPV • 70% of women cleared HPV within 24 months

25. Most adolescents will clear HPV spontaneously • Brown et al, J Infectious Dis 2005 (teens) • Average duration of HPV infection was 168 days

26. Most adolescents will clear HPV spontaneously • Insinga et al, Cancer Epidemiol Biomarkers Prev 2007 • 2391 women aged 16-23 in HPV vaccine trial placebo arm • Q6 mo eval x 4 years • Mean durations for HPV 16 and 18 were 18 and 16 months respectively • 85-90% cleared within three years

27. Insinga et al

28. Moscicki 2004 Lancet, 187 women aged 13-22 Median follow-up of 61 months 61% of LSIL regressed at 12 months 91% regressed by 36 months Cytologic (pap) abnormalities also spontaneously clear in adolescents

29. Cytologic (pap) abnormalities also spontaneously clear in adolescents • Winer et al, J Infectious Dis 2005 (college) • Mean duration of LSIL was 5 months • 86% cleared their SIL • less than 9% developed CIN 2/3 in 4 yrs

30. Even histologic dysplasia will spontaneously clear in adolescents • Moore 2007 AJOG • 177 Adolescents with biopsy-proven CIN 2 • Given opportunity to choose LEEP or observation • Followed for 18-26 months

31. Even histologic dysplasia will spontaneously clear in adolescents Fuchs 2007 J Pediatr Adolesc Gyn • Adolescents with CIN2 • Observed, not treated • 39% regr at 1 yr • 50% at 2 yrs • 75% at 3 yrs

32. Even histologic dysplasia will spontaneously clear in adolescents

33. Ok, but what about those 10-15% whose HPV or dysplasia didn’t clear within 3-4 years? No worries

34. Cervical Cancer takes time to develop • Is a result of PERSISTENT HPV infection • Adolescents get a lot of HPV, BUT in the majority, it does not persist • In those in whom it does persist, cervical cancer takes years to develop (analogy to colon cancer) • Remember, in the studies cited, none of the women who were simply observed (including the 5% who progressed) developed cancer • Therefore, cervical cancer is virtually non-existent in adolescents

35. Cervical CA is almost nonexistent under age 21 Watson et al, Burden of cervical cancer in the United States 1998-2003. Cancer 2008

36. SEER Cervical Cancer Data (Rates per 100,000 women)

37. Comparison of Cancer Incidence in Adolescents (rate per 100,000) www.seer.cancer.gov

38. But can’t we just screen anyway? • It’d make me feel a lot better. • (I know she’s been having sex for years!) • And it’s just a pap smear! • I have to do a pelvic to screen for STI’s anyway, right? Wrong! • And don’t you have to do a pap smear before you prescribe birth control pills? NO! • I mean really, what harm can it do?

39. Unnecessary screening and treatment can have significant morbidity • Cost, hassle • Fear of exams & fear of providers = barrier to accessing sexual health care (contraceptive counseling and provision, STI counseling and testing, vaginal health) • “Emotional impact of labeling an adolescent with both a sexually transmitted infection and a potential precancer must be considered because adolescence is a time of heightened concern for self-image and emerging sexuality.” (ACOG Practice Bulletin) • Adverse obstetrical outcomes in a population whose childbearing years are still ahead of them

40. Adverse OB outcomes from cervical cancer screening and resultant treatment - Kyrgiou Lancet 2006

41. So…. • Screening for a disease that practically doesn’t exist in that age group (under 21) does not make sense • And it can cause unnecessary grief and harm, as well as cost

42. Start screening at 21 In short, we don’t want to know what’s going on before then because it will probably go away on its own! (And we’re more likely to cause unnecessary harm than we are to find significant disease.) All we are saying… is give teens a chance!

43. Screen every two years(ages 21-29)After age 30, if 3 consecutive normals, screen every 3 years

44. Exceptions • The following groups typically need annual pap screening due to increased risk of CIN: • HIV positive • Immunosuppression (transplant recipients) • DES exposure (not relevant to student health) • Previously treated for CIN2, CIN3, or Cancer

45. 30-Somethings are different from 20-somethings! • More likely to be monogamous (not being exposed to HPV, or at least not to new HPV) • More likely to have already had HPV infection at some point and perhaps have some immunity • Less likely to be able to spontaneously clear a new HPV infection • Overall have a higher incidence of cervical cancer (likely reflecting persistence of disease that began in their 20’s)

46. Going the distance: How often to screen? • How predictive is a normal pap smear? • For how long after a normal pap smear can you feel reasonably confident that you haven’t developed cervical cancer? • Depends on two factors: • Sensitivity of the pap (how much faith can you put in a normal one) • Virulence or aggressiveness of HPV/cervical dysplasia (how long does it take to turn really bad?)

47. Going the distance: How often to screen? • In the past 10 years, many studies have been conducted to try to answer this question, thanks, in large part, to a study done 15 years ago…

48. Cancer 1987, EddyThe Frequency of Cervical Cancer ScreeningComparison of a Mathematical Model with Empirical Data Found that previous models under-estimated the effectiveness of screening at less than annual intervals, spurred interest in revisiting the wisdom of annual screening.

49. Sawaya 2000 Obstetrics and Gynecology Prospective cohort study of 128,000 women in the CDC Breast/Cervical Cancer Program

50. Sawaya 2000 Prospective cohort study of 128,000 women in the CDC Breast/Cervical Cancer Program No statistically significant difference in rate of high grade abnormalities among the different screening intervals.