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/Screening-Guidelines .

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 YEARSWHY?

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 colposcopyfrom 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 HPVWHY?

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 co-test again in 3 years. (Routine screening would be Q5 yrs >30 yrs of

age) (This applies to ages 21-29 as well, which is

routine screening for them)

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 yAge 30-65:- q5 y co-

testing- q3 y cytology

Age 21-29: q3 yAge 30-65:- q5 y co-

testing- q3 y cytology

Age 21-29: q3 yAge 30-65:- q5 y co-

testing- q3 y cytology

When to stop? Age 65 yrs if adequate negative ORHysterectomy if no h/o of CIN 2+

Age 65 yrs if 3 consecutive (-) pap or 2 consecutive (-) co-test w/in 10 yrs ORHysterectomy if no h/o of CIN 2+

Age 65 yrs if 3 consecutive (-) pap or 2 consecutive (-) co-test w/in 10 yrs ORHysterectomy 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/Screening-Guidelines

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/Management-Guidelines-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