Update:Pap Smear Guidelines

1. Update:Pap Smear Guidelines Anoop Agrawal, M.D.

2. Pap Smear Guidelines • American College of Obstetrics and Gynecology (ACOG) – released new guidelines in November 2009 • U.S. Preventative Services Task Force (USPSTF) – last published in 2003 • American Cancer Society (ACS) – last published in 2002. • Guidelines in this review based upon the ACOG revision.

3. Cervical Cancer Trends • Rate of cancer has decreased by more than 50% in past 30 years • 1975 – incidence was 14.8 per 100,000 • 2006 – incidence was 6.5 per 100,000 • Estimates for 2009 • 11,270 new cases with 4,070 deaths in U.S. • 500,000 new cases with 240,000 worldwide • Women who are immigrants to the US are especially high-risk group due to variable screening in their country of origin.

4. HPV and Cervical Neoplasia • The HPV type and persistence of HPV infection are the main determinants of cervical neoplasia. • There are 15-18 “high-risk” types of HPV confirmed to be oncogenic agents. • Other factors that may play a role are smoking and immunosuppression. • Adolescents and young women with normal immune systems will likely clear the infection within 8-24 months. • In this group, HPV infections and dysplasia will likely resolve spontaneously.

5. Paps in the era of HPV Vaccination • Theoretically, a reduction in cervical cancer will not begin to be seen for another 15-20 years following a widely implemented vaccination program. • Women who have been vaccinated should be screened by the same regimen as non-immunized women. (Level C)

6. Pap Smear Techniques • Two techniques: • Liquid-based • Conventional method • Majority of screening in U.S. is now liquid-based. • Studies have found no significant difference in sensitivity or specificity between the two techniques. • Lubricant may be used on the speculum however... lubricant on the cervix will interfere with the transfer of cells and lead to false results.

7. Case One • An 18 yo hispanic female presents with vaginal discharge. She has a history of chlamydia and reports ‘37’ sexual partners. You plan to perform a pelvic exam and obtain samples for STDs. When should she begin cervical cancer screening? • Cervical cancer screening should begin at age 21 years. (Level A)

8. Why wait till 21 years old? • Sexually active adolescents have a high rate of infection with HPV, but… • Invasive cervical cancer is very rare in women younger than 21 years. • 0.1% of cases occur before 21 years. • Data from CDC from ‘98-’03 found 14 cases/yr in females aged 15-19 years. • Surveillance Epidemiology and End Results (SEER) data from ‘02-’06 shows incidence rate of 1-2 cervical cancer cases per 1,000,000 females aged 15-19 years

9. Why wait till 21 years old? • Recommendation to wait till 21 also based on potential for adverse effects associated with follow-up interventions • Recent studies have documented a significant increase in premature births in women previously treated with excisional procedures for dysplasia. • Earlier onset of screening may increase anxiety, morbidity and expense from the test itself and overuse of follow-up • These patients should still have testing for STDs. In asymptomatic patients, can be done without use of a speculum.

10. Case Two • A 25 yo white female presents for her annual physical exam. She reports a history of ASCUS in the past. Her last pap smear was one year ago and was normal. Should you perform her pap smear today? • No. Cervical cancer screening is recommended every 2 years for women aged 21-29 years. (Level A)

11. Frequency of Cervical Screening • Screening every 2 years for women aged 21-29 years. • Women aged 30 years and older who have had 3 consecutive negatives may be screened every 3 years. • Exceptions are: • HIV • Immunosuppressed • Exposed to diethylstilbesterol in utero • Previously treated for CIN 2, CIN 3, or cancer • All of the above recommendations are Level A.

12. Data for Cervical Cancer Screening • National Breast and Cervical Cancer Early Detection Program: • In 31,728 women aged 30-64 years found prevalence of CIN 2 and 3 of 0.028% and 0.019% in those who had three annual negative Pap tests in a row. • No cases of invasive cancer in this group. • The calculated risk based on computer models with this data estimate 4 women with cancer per 100,000 over the next 3 years with annual screening. • With triennial screening, estimate 8 per 100,000. • Though this is a doubling, the absolute number of cases is small and the estimated cost of finding each additional case of cancer was large.

13. Case Three • A 57 yo African-American female is here for her annual check-up. She reports having had a hysterectomy ‘some years ago’ for ‘pre-cancerous lesions.’ Does she still need cervical cancer screening? • Yes. Women who have had a hysterectomy and due to a history of CIN 2 or CIN 3 need continued ANNUAL screening. (Level B)

14. Woman with Hysterectomy • Women who have had a total hysterectomy for benign indications and have no prior history of high-grade CIN should discontinue screening. (Level A) • Primary vaginal cancer is very rare. • Of 6,543 women with hysterectomies for benign reasons, only 1.8% had an abnormal cytology and 0.12% had vaginal intraepithelial neoplasia on biopsy.

15. Case Four • A 67 yo female presents for annual physical. She is wondering when she can stop having Pap smears performed. She has had regular screening throughout her life. What do you advise? • You may discontinue screening at either 65 or 70 years of age in women who have had three or more negative cytologic test results in a row and no abnormal test results in past 10 years. (Level B) • Risk factors should be reassessed during the annual exam to determine if reinitiating screening is appropriate.

16. Case Five • A 17 yo female had a Pap smear performed at another facility. The results showed ASC-US with positive reflex HPV testing. She has come in for follow-up. What do you recommend for further management? • Ignore the results and resume cervical cancer screening at age 21 years. • HPV testing should not be used in women younger than 21 years. If inadvertently performed, a positive result should no influence management.

17. HPV Testing • Reflex HPV DNA testing serves as a useful triage test to stratify risk to women • aged 21 years and older with a ASC-US • postmenopausal women with LSIL • Also has proven role in primary screening in women older than 30 years. • Women with both negative cervical cytology and HPV DNA testing are extremely low risk for CIN 2 or CIN 3 during the next 4-6 years. • This is lower risk than women who have only had a negative cytology. • Women over 30 years with negative cytology and HPV should be rescreened no sooner than 3 years. (Level A)

18. Conclusions • New guidelines are designed to better balance the risks and benefits of screening based on newer data. • Cervical cytology screening should begin after age 21 years. • For women between age 21-29 years with average risk, cervical cytology screening should be every 2 years. • For women 30 years and older, screening may be every 3 years if they have had at least 3 negative screens prior. • Women with total hysterectomies for benign reasons do not need any further screening.

19. References • American College of Obstetrics and Gynecology. ACOG Practice Bulletin 109, December 2009: cervical cytology screening. Obstet Gynecol 2009;114:1409-1420. • Sawaya GF. Cervical Cancer Screening – New guidelines and the balance between benefits and harms. N Eng J Med 2009;361:2504-5.