Cervical Cancer Screening Update

Report
CERVICAL CANCER SCREENING
UPDATE
Based on the 2012 Recommendations (ASCCP)
Sarah Lamanuzzi, MD, FAAFP
DISCLOSURES

I have no disclosures other than: the ASCCP gave
permission for use of their slide content.

The American Society for Colposcopy and Cervical
Pathology. “Cervical Cancer Screening
Recommendations, 2012”
http://www.asccp.org/Guidelines/ScreeningGuidelines .
OBJECTIVES
Highlight changes in the guidelines for cervical
cancer screening and comparison of guidelines
between agencies
 Explain some of the reasoning behind the
changes
 Take-home points for cervical cancer screening

WHAT ARE THE BENEFITS IN SCREENING
FOR CERVICAL CANCER?
WHAT IS THE IMPORTANCE OF CERVICAL
CANCER SCREENING?

Highest risk for developing Cervical Cancer:
being rarely or never screened.

Least likely to be screened:






Minorities
Low socioeconomic status/uninsured
Recent immigration (<10 yrs in US)
No usual source of health care
The American Society for Colposcopy and Cervical Pathology. “Cervical Cancer
Screening Recommendations, 2012.”
NB: Kaiser study of women with cervical cancer
noted that 56% had not ever had a pap smear.

81% of those had seen a provider in the KP system
Leyden MA, Manos M, Kinney W et al. J Natl Cancer Inst. 2005; 97:67583.
WHAT ARE THE HARMS OF CERVICAL
CANCER SCREENING?

ASCCP: Uses colposcopy as marker of harm.
Anxiety associated with false positive cancer screening test
 Potential stigmatization from diagnosis of STI
 Discomfort &/or bleeding from additional diagnostic &
treatment procedures
 Increased risk of pregnancy complications due to treatment

ACOG: harms not stated in the 2012 guidelines
 USPSTF:

False positive results leading to frequent testing & invasive
procedures & the harms of those (bleeding, pain, infection,
failure to dx; anxiety, distress, concern about health)
 Adverse pregnancy outcomes
 Over-diagnosis (many lesions regress spontaneously)/
overtreatment

National Guideline Clearinghouse. “Guideline Synthesis: Screening for Cervical Cancer in
Women at Average Risk.” http://www.guideline.gov/syntheses/synthesis.aspx?id=43606 .
HOW DID THEY DECIDE TO CHANGE
EVERYTHING?



Team from ASCCP, ACS, and ASCP
Literature review from 1995 – 2011 (graded evidence)
Consensus when reviewing literature:
We can’t prevent every case of cervical cancer
CIN3 is a reliable surrogate for cervical cancer
Risk of developing invasive cancer before next screen should be
unlikely
 # of colposcopies ~ marker for harm




6 topics of interest:




Optimal screening interval
Screening age 30+
Impact of HPV vaccination
on screening
Potential for HPV testing
alone (no pap)
Exiting women from
screening
 Managing discordant
cytology & HPV results

TWO AREAS THAT NEED MORE STUDY:

Impact of HPV
vaccination:
 “Recommended
screening practices
should not change on
the basis of HPV
vaccination.”



Paavonen J et al. Lancet
2009; 374: 301-314.
Decreases CIN3 and
colposcopy but no reliable
way to confirm full
vaccination series.

HPV testing alone:
 Strong negative
predictive value, so it
may replace co-testing
in the future BUT:
 Test specificity is
lacking
 Appropriate follow-up
is not yet known
 Knowledge of HPV
status affects
interpretation of
cytology
It is NOT recommended
to test with HPV alone.
WHAT ARE THE MAJOR CHANGES IN
CERVICAL CANCER SCREENING?

Do not start cervical cancer screening until age
21 regardless of sexual activity status.


(Does not apply to special populations: DES exposure, immune
compromised, history of cervical cancer)
Screening in ages 21-29 should be:
Cytology every 3 years
 Not co-testing (or HPV alone)


Screening in ages 30-65 should be:
Co-testing (cytology+HPV) every 5 years (preferred)
 Cytology alone every 3 years (acceptable)


Discordant cytology (pap) & HPV management
recommendations
WHAT ARE THE MAJOR CHANGES IN THE
UPDATED GUIDELINES? (CONT.)
Stop screening at age 65 if acceptable prior
negative testing
 Stop screening after hysterectomy for benign
causes if no CIN2 or above within 20 yrs.
 Continue screening after age 65 if within 20
years of CIN2+ diagnosis.

DO NOT START CERVICAL CANCER SCREENING
UNTIL AGE 21 REGARDLESS OF SEXUAL
ACTIVITY STATUS.
WHY?
Cervical Cancer Incidence by Age Group (USCS), 1998-2002
Age
Incidence per 100,000
0-19
0.1
20-29
4.5
30-39
13.9
40-49
16.5
50-64
15.4
65+
14.6
All ages
9.4
United States Cancer Statistics includes data from CDC’s National Program of Cancer
Registries and NCI’s Surveillance, Epidemiology and End Results Program.
Saraiya M et al. Obstet Gynecol 2007; 109:360-70.
DO NOT START CERVICAL CANCER SCREENING
UNTIL AGE 21 REGARDLESS OF SEXUAL
ACTIVITY STATUS.
TREATMENT OF ADOLESCENTS
STI screening as recommended (urine)
 Contraceptive management
 No pap tests
 No speculum exams for asymptomatic women

SCREENING IN AGES 21-29: Q3 YEARS
WHY?

Sensitivity of single pap test: 50-70%
Cancer risk 18 mo after 3 neg paps: 1.5/100,000
 Cancer risk 36 mo after 3 neg paps: 4.7/100,000
 99,997 screened unnecessarily to help 3


Risk of HSIL/cancer < 3 years after neg pap not
significantly higher than after 1 year
Sawaya GF et al. Acta Cytol 2005: 49: 391-7.
There is also a much decreased incidence of lifetime-risk of colposcopy
from 2000 per 1000 women (with annual screening) to 760 per 1000 women
(with q3 year screening).
Stout NK et al. Arch Intern Med 2008; 168:181.
Kulasingam S et al. 2011. AHRQ Publication No. 11-05157-EF-1.
SCREENING IN AGES 21-29: REFLEX HPV
WHY?

Co-testing NOT recommended b/c:


Carcinogenic (high-risk) HPV incidence nearly 20%
in teens and early 20s & most resolve w/o tx.
Reflex HPV testing (with ASCUS or LSIL) allows
for differentiating management of the abnormal
cytology.
Weighted Prevalence of High-Risk HPV among
US Women, 2007-2010 (NHANES)
Age
Weighted Prevalence
14-19
~25%
20-24
~45%
25-29
~30%
Adapted from: Hariri S et al. J Infect Dis 2011; 204:566-573.
SCREENING AGES 30-65:
CO-TESTING Q5 YRS.
WHY?

Co-testing = cytology plus testing for HR-HPV
Equivalent risk of CIN3 as q1-3 year cytology alone
 Increases detection of CIN3 and AIS
 Decreased incidence of CIN3 in subsequent screening
 Minimizes the number of colposcopies


Histological progression in this age group:


< 10% progress over 30 months
~70% clear completely over 30 months
Rodriguez AC et al. J Natl Cancer Inst. 2008; 100: 513-517.
SCREENING AGES 30-65: OPTION Q3 YR
WHY?


Financial and / or logistical barriers to HR-HPV
co-testing
Cytology is still effective (q3 yrs) acknowledging
that there are:
Increased frequency of visits
 Increased number of colposcopies for equivocal
cytology results

DISCORDANT CO-TESTING RESULTS:
NEGATIVE CYTOLOGY/(+) HR-HPV

Normal pap smear with (+) HR-HPV has 2
options for follow-up:

Repeat co-testing in 12 months


If abnormal, colposcopy. If normal, routine screening
Immediate genotyping (16/18) of HR-HPV
If (+)16 or 18, colposcopy. If normal, repeat co-testing 12 mo
 If repeat co-testing abnormal, colpo. If rpt co-test nl, routine


* Direct referral to colposcopy is not indicated.
DISCORDANT CO-TESTING RESULTS:
ASCUS PAP / (-) HR-HPV

These women can follow age-specific routine
screening


Q5 yrs >30 yrs of age (co-testing)
The risk of CIN3 in women in this situation is
less than 2% (lower than threshold for
colposcopy).
STOP SCREENING AT AGE 65 IF NORMAL PRIOR.
WHY?

Stop screening at age 65 if acceptable prior negative
testing
no history of CIN2 or above within last 20 yrs
 3 consecutive (-) pap or 2 consecutive (-) co-test w/in 10 yrs

Screening “should not resume for any reason, even if a
woman reports having a new sexual partner”
 CIN2+ is rare after age 65
 HPV risk still 5-10% but unlikely to lead to cancer
within remaining lifetime
 Colposcopy more difficult (increases harm)

Chen HC et al. J Natl Cancer Inst. 2011; 103: 1387-1396.
Rodriguez AC et al. J Natl Cancer Inst. 2009; 101: 721-728.
STOP SCREENING AFTER HYSTERECTOMY
FOR BENIGN REASONS.
WHY?
Stop screening after hysterectomy (including
cervix) and no history of CIN2+.
 No evidence of prior negative screening required.
 Over 600 vaginal cuff paps required to find 1
VAIN (another study – over 2000 women followed
>5 y: no vaginal cancer, 3% VAIN)
 Similar to risk of breast cancer in men, in which
regular screening is not recommended.

Pearce KF et al. NEJM 1996; 335: 1559-1562.
Piscitelli JT et al. AJOG 1995; 173: 424-430.
CONTINUE SCREENING AFTER AGE 65 IF
H/O CIN2+ WITHIN 20 YRS.
WHY?
If history of CIN2, CIN3, or AIS within the last
20 years, even if it extends screening past age 65.
 Women treated for CIN2+ within 20 yrs still have
a 5 to 10-fold higher risk for cervical cancer than
the general population.
 Testing is “routine” for ages 30-65 unless
abnormal results are obtained.

SUMMARY OF SCREENING UPDATES:
Do not start cervical cancer screening until age
21 regardless of sexual activity status.
 Screen Q3 yrs (pap) in ages 21-29.
 Co-test Q5 yrs in ages 30-65 (or pap Q3 yrs).
 ASCUS with (-) HR-HPV: routine screening
 Pap (-) with (+) HR-HPV:



Repeat co-testing in 12 months OR
Immediate genotyping (16/18) with colpo if (+)
Stop screening at 65 or after hysterectomy
 Continue screening after 65 or after
hysterectomy only if (+) CIN2+ w/in 20 yrs

Summary of 2012 Cervical Cancer Screening Recommendations
USPSTF
ASCCP
ACOG
When to start?
Age 21
Age 21
Age 21
How often?
Age 21-29: q3 y
Age 30-65:
- q5 y co-testing
- q3 y cytology
Age 21-29: q3 y
Age 30-65:
- q5 y co-testing
- q3 y cytology
Age 21-29: q3 y
Age 30-65:
- q5 y co-testing
- q3 y cytology
When to stop?
Age 65 yrs if
adequate
negative OR
Hysterectomy if
no h/o of CIN 2+
Age 65 yrs if 3
consecutive (-)
pap or 2
consecutive (-) cotest w/in 10 yrs
OR
Hysterectomy if
no h/o of CIN 2+
Age 65 yrs if 3
consecutive (-)
pap or 2
consecutive (-) cotest w/in 10 yrs
OR
Hysterectomy if
no h/o of CIN 2+
MANAGEMENT OF ABNORMAL PAP SMEAR
(CYTOLOGY):
2012 recommendations for management of
abnormal pap smears are more complex than
previous, and they differ by cytology, by age, and
by HR-HPV status.
 ASCCP has free printable PDF of tx algorithms
(can buy in pamphlet form).

WHERE CAN WE FIND THESE UPDATES?
PRIMARY REFERENCES

Saslow, Solomon, Lawson et al. “American
Cancer Society, American Society for Colposcopy
and Cervical Pathology, and American Society for
Clinical Pathology Screening Guidelines for the
Prevention and Early Detection of Cervical
Cancer.” (online March 2012) JLGTD 2012; 16(3): 00-29.
http://www.asccp.org/Guidelines/ScreeningGuidelines

Massad et al. “2012 Updated Consensus
Guidelines for the Management of Abnormal
Cervical Cancer Screening Tests and Cancer
Precursors.” JLGTD 2013; 17(5): S1-S27.
http://www.asccp.org/Guidelines-2/ManagementGuidelines-2
REFERENCES (CONT.)

National Guideline Clearinghouse. “Guideline
Synthesis: Screening for Cervical Cancer in
Women at Average Risk.”
http://www.guideline.gov/syntheses/synthesis.aspx?id=43606 .
QUESTIONS?
Contact information:
Sarah Lamanuzzi, MD
slamanuzzi@kodfp.org
@sarahlamanuzzi

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