Cervical Cancer Screening Update

1. Cervical Cancer Screening Update Based on 2012 Guidelines & Recommendations Sarah Lamanuzzi, MD, FAAFP

2. 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 .

3. 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 • Address how cervical cancer screening fits into the goals of the Triple Aim for health reform

4. Triple Aim for Health Reform • Improving the patient experience of care (including quality and satisfaction) • Improving the health of populations • Reducing the per capita cost of healthcare Institute for Healthcare Improvement (IHI)

5. What are the Benefits in screening for cervical cancer?

6. 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.

7. 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 .

8. 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. • The risk of developing invasive cancer before next screen should be unlikely. • Performance of colposcopy = marker for harm.

9. How did they decide to change everything? • 6 topics of interest during literature review: • Optimal screening interval • Screening age 30+ • Managing discordant cytology & HPV results • Exiting women from screening • Impact of HPV vaccination on screening • Potential for HPV testing alone (no pap)

10. Areas that need more study:Impact of HPV Vaccination • HPV Vaccination is effective – we have seen decreases in CIN3 and in performance of colposcopy • But … • There is no reliable way to confirm a full vaccination series • We do not yet know if partial series confer as much protection • “Recommended screening practices should not change on the basis of HPV vaccination.” • Paavonen J et al. Lancet 2009; 374: 301-314.

11. Areas that need more study: HPV Testing Alone • It is not currently recommended to test with HPV alone. • Negative HPV testing has a strong negative predictive value; it may replace or augment other screening methods in the future BUT: • Test specificity is lacking • Appropriate follow-up is not yet known • Knowledge of HPV status affects interpretation of cytology • The FDA recently recommended HPV testing alone as a means of cervical cancer screening • The ASCCP and other organizations are reviewing the studies but there is not yet a consensus update on this recommendation

12. 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

13. 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.

14. Do not start cervical cancer screening until age 21 regardless of sexual activity status.Why? 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.

15. 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

16. 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 is not significantly higher than after 1 year • Sawaya GF et al. ActaCytol 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.

17. 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. Adapted from: Hariri S et al. J Infect Dis 2011; 204:566-573.

18. 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.

19. Screening ages 30-65: option q3 yrWhy? • 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

20. Discordant Co-testing Results:Negative Cytology/(+) HR-HPV • Normal pap test with (+) HR-HPV has 2 options for follow-up: • Option 1: Repeat co-testing in 12 months • If abnormal, colposcopy. If normal, co-test in 3 yrs. • Option 2: Immediate genotyping (16/18) of HR-HPV • If (+)16 or 18, colposcopy. If normal colposcopy, repeat co-testing 12 months. • If (-) 16 or 18, repeat co-testing in 12 months. If abnormal, colposcopy. If repeat co-test normal, repeat in 3 yrs. • * Direct referral to colposcopy is not indicated.

21. 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 high negative predictive of negative HR-HPV testing allows us not to re-test in 12 months • The risk of CIN3 in women in this situation is less than 2% (lower than threshold for colposcopy).

22. 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.

23. 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.

24. 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.

25. 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: repeat in 3 yrs. • 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

27. Management of Abnormal Pap Test (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).

28. Cervical Cancer Screening & the Triple Aim • Improving the patient experience of care (including quality and satisfaction) • Fewer pap smears & colposcopies = happy women • Improved understanding of screening = better quality of care • Improving the health of populations • Remembering to “add in” cervical cancer screening when seeing women for other reasons leads to improved health (fewer cases of cervical cancer) • Reducing the per capita cost of healthcare • Fewer pap smears & colposcopies = lower cost with similar (maybe even better) health outcomes

29. 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 • National Guideline Clearinghouse. “Guideline Synthesis: Screening for Cervical Cancer in Women at Average Risk.” http://www.guideline.gov/syntheses/synthesis.aspx?id=43606

30. Questions? Contact information: Sarah Lamanuzzi, MD, FAAFP slamanuzzi@kodfp.org @sarahlamanuzzi