Erica Nelson, M.D.
Dept. of Obstetrics & Gynecology
SIU School of Medicine
Springfield, IL
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
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
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
15-19 yrs
0.3 per 100,000
20-24 yrs
2.6 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 All Races
What were the old standards?
When to
start?
1987
18yo or at
sexual
debut
2002
21yo or 3y after sex
How often?
Annually
When to
stop?
???
Annually till 30 (Q2y if LBP)
Q3y after 3neg unless DES/HIV+
Q3y if Pap/HPV test
Age 70 if 3 prior consecutive/sat/
documented neg Paps within 10
years
After hyst for benign dis
American Cancer Society, 1987, 2002
How well did the old standards
work?
Cervical cancer was once the leading cancer
killer of U.S. women
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
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
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
What is the natural history of
LSIL/CIN1 in adolescents?
Moscicki AB et al. Lancet 2004;364:1678-83
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
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
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 2530 years of age

Sasieni et al BMJ 2009;339:328
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
 Won’t be treated unless we find CIN3
 And don’t benefit from screening because they only
die from rapid-onset cancers Paps miss
Maybe we shouldn’t be looking!
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 <5% and by <3 days
costs >$500,000/LY
Prevents 1 cancer in every 33,333 women screened
 Eddy Ann Int Med 1990;113:214-26
 Chan et al ObGyn 2003;102:765-73
So why change (VI)?
Treatment saves lives but also
costs lives
 Women with LEEP more likely to have
 Preterm birth (O.R. 1.7)
 LBW (O.R. 1.8)
 PPROM (O.R. 2.7)
 Single studies show association with perinatal death,
incompetent cervix
 Risk rises with depth, # LEEPs
 Similar findings after CKC or laser cone
 Absolute risk increase is small
Kyrgiou M et al. Lancet 2006;367:489-98 and Bruinsma et al BJOG 2007;114:70-80
Changes from 2002 guidelines
 Later start to screening
 21yo--previously 3y after sex or 21yo
 Longer screening intervals
 Screen q2y ages 20-29—was annually
 “May” screen q3y 30-70 (after 3 consecutive neg Paps and
no CIN2,3/immunocompromise/DES
 Screen annually after CIN2,3/Ca for at least 20y
 Conventional and liquid-based Paps equivalent
When to start screening
 “Begin at age 21 years”
 Sexually active adolescents need care for
contraception and STD screening/treatment
 These don’t require Pap testing
 No speculum needed in asymptomatic pt
 STD testing can be done using urine
Rationale for later screening start
 Cervical cancer rare in teens (<1:1,000,000)
 HPV—including HRHPV occurs in over 80% of
sexually active adolescents
 HPV infections usually transient
 Europeans start at 25-30 years of age
 Screen only every 3-5 years
 But they have central screening systems
Rationale for later screening start
 Overdiagnosis may lead to overtreatment
 Overtreatment may cause preterm delivery
 Upper age limit protects women/providers unwilling
to discuss onset of sex.
 Screening virgins optional, based on “provider
discretion and patient choice.”

What is “sex” and who is a virgin?
Rationale for longer interval
 Sensitivity of single smear only 50-70%
 Risk of cancer within 3 years of 3 neg Paps only 1/100,000
 Risk of progression to HSIL/cancer <3y after
negative Pap not significantly higher than after 1y
 Longer screening intervals (e.g., 5y) inappropriate
for mobile US population
 Smoking, sexual risks “should not be used” to
justify more frequent screening.
 LBC may be more sensitive than conventional Pap
When to stop screening
 If life-threatening illness at any age
 At 70yo if
 Intact cervix
 3 or more documented, satisfactory, negative cytology
tests within 10y
Must screen women without documentation
When NOT to stop at 70yo
 History of
 Prior Cervical or endometrial cancer
 In utero DES exposure
 HIV infection or other immunocompromise
 Possibly if high risk HPV+
 No comment on what to do if Hx CIN
 ASCCP recommends screening “at least 20y” after
treatment for CIN
Rationale for stopping at 70yo
 Most cervical cancers in older women occur in
underscreened populations (poor, minority)
 New high risk HPV infections and de novo CIN unlikely in
older women
 When they occur, they are unlikely to progress to cancer
before 15-20 years (competing mortality risk)
Screening after hysterectomy
 “Screening . . . following total hysterectomy for
benign gynecologic disease is not indicated.”
 Path should exclude cervical neoplasia
 Women with SC hyst continue screening
 Women with CIN2/3 continue until 3 negs and no
abnormal smears within 10y
 Women with DES exposure or CaCx continue
screening as long as healthy
Rationale for stopping after hyst
 Incidence of vaginal cancer 1-2/100,000/yr
 Less common than small bowel cancer
 Since a priori risk for VAIN is very low, most abnormals
are falsely positive.
 Abnormal Pap will lead to painful colpo, more intensive
Pap surveillance, treatments that risk bladder/rectal
injury, more cost
 Other indications for gyn visits may remain
Reasons to ignore guidelines
 People only think in 1-year cycles
 BMD testing
 Colonoscopy
 We need to make sure nothing is missed
 Daily Pap testing?
 Screening colposcopy or LEEP?
 No cost is too high, either from altruism or defensive
medicine
 Convince mothers with PTD after LEEP
Reasons to ignore guidelines
 Women get HPV after age 70
 But the natural history of HPV doesn’t change
 It still requires decades to progress from infection to
integration to mutation to invasion to death
 Recall the objective of screening: to prevent
morbidity/mortality from cervical cancer
 Mortality over 25 years after age 70 is HIGH
 Treatment in the very elderly is very difficult
Reasons to ignore guidelines
 My patients are high risk
 All women are high risk. Sensitivity of screening is
adequate even for women with risk factors, given slow
progression of precursors. (But follow guidelines for
managing abnormal results!)
 Women want to know if they have HPV
 They have it. Diagnosing an incurable STD results in
stigmatization without changing cancer risk or
improving quality of life.
 Annual visits are important for other reasons
 This is too complicated . . .
Conclusion
 “The biggest gain in reducing cervical cancer
incidence and mortality would be achieved by
increasing screening rates among women who have
not been screened or who have not been screened
regularly. . . Clinicians, hospitals, health plans, and
public health officials should seek to identify and
screen these women.”
ACS, 20002