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Erica Nelson, M.D. Dept. of Obstetrics & Gynecology SIU School of Medicine Springfield, IL

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Disclosure No disclosures Some slides were prepared by ASCCP through its Educate the Educators program Funded by Merck, Digene, & Roche ASCCP controlled content: no industry input

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Objective Participants should be able to screen women for cervical cancer, applying the epidemiology and natural history of human papillomavirus infections and of consequent preinvasive and invasive cervical cancers that underlie new ACOG guidelines

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What is the objective of screening? To reduce morbidity/mortality from cervical cancer Not to find CIN or abnormal Paps Not to find HPV infection

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15-19 yrs0.3 per 100,000 20-24 yrs2.6 per 100,000 25-29 yrs 7.8 per 100,000 30-34 yrs 11.4 per 100,000 35-39 yrs 14.4 per 100,000 *SEER 1992-1996 A ll Races

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What were the old standards? American Cancer Society, 1987, 2002 19872002 When to start? 18yo or at sexual debut 21yo or 3y after sex How often?AnnuallyAnnually till 30 (Q2y if LBP) Q3y after 3neg unless DES/HIV+ Q3y if Pap/HPV test When to stop? ???Age 70 if 3 prior consecutive/sat/ documented neg Paps within 10 years After hyst for benign dis

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How well did the old standards work? Cervical cancer was once the leading cancer killer of U.S. women

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Residual risk >1,000,000 abnormal Paps annually >400,000 CIN2,3 annually Many are cervical cancers that screening/Rx will prevent Cervical cancer risk in unscreened women remains high >50% of cervical cancers in un/underscreened women About 12% of cancers follow mismanaged abnormals Only about 30% of cancers are screen failures Spence et al. Prev Med 2007;45:93-106

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So if screening works, why change? (I) Better understanding of HPV natural history Most women contract HPV within 2y of first sex Most contract high risk types, esp. HPV 16 Most women clear HPV within 2 years of infection Only persistent HRHPV infections cause cancer Diagnosing a transient viral infection may lead to treatment that has no impact on cancer risk Even if a lesion is found Even if CIN1 or (sometimes) CIN2 is present

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So why change (II)? Better understanding of CIN natural history, esp. clearance rates >75% of CIN1 regress without treatment Only 10% develop CIN3 within 2y (no cancers) Most are rapid-onset CIN are HPV infections with little neoplastic potential >65% of adolescents clear CIN2 within 3y >50% of adults clear CIN2 without treatment

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What is the natural history of LSIL/CIN1 in adolescents? Moscicki AB et al. Lancet 2004;364:1678-83

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What is the natural history of CIN2 in adolescents? 23 adolescents followed median of 18m 65% of CIN2 regressed 17% had persistent CIN2 13% progressed to CIN3 None had cancer Avoid loss to follow-up AND overtreatment Moore et al. AJOG 2007;197:141.e1.e6

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So why change (III)? New 2006 ASCCP management guidelines: For adolescents with ASC/LSIL/CIN1, follow Paps annually For adolescents with CIN2, CIN2,3 and satisfactory colpo, follow Pap/colpo q6m: no Rx Observe young women with HSIL/CIN2,3 desiring pregnancy without treatment

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So why change (IV)? Better grasp of the futility of early screening Cervical cancer screening has little or no impact on rates of invasive cervical cancer up to age 30. OR for future cervical cancer, screened vs not For women 20-21: 1.5 For women 20-24: 1.1 But a significant reduction after age 30 Many European health programs delay screening till 25- 30 years of age Sasieni et al BMJ 2009;339:328

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So why change (IV)? So if young women Have lots of HPV including HRHPV Have lots of abnormal cytology and CIN1-2 Clear most HPV, ASC, LSIL, and CIN1-2 Wont be treated unless we find CIN3 And dont benefit from screening because they only die from rapid-onset cancers Paps miss Maybe we shouldnt be looking!

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So why change (V)? Better appreciation of cost effectiveness and marginal benefit of annual testing Q3y screening reduces cervical cancer mortality risk by 10-20% and increases life by 100 days compared to no screening Compared to q3y screening, annual screening improves life expectancy by