9/18/2008. Cervical Cancer Prevention for Adolescent Populations Garcia. Faculty disclosure. Objectives. HPV Positivity by Age (UK)

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Faculty disclosure Cervical Cancer Prevention for Francisco, MD, MPH Associate Professor Obstetrics &

disclose Note: Additional disclosure information is located within the program Objectives Review the

NIH/ASCCP Guidelines recommendation for Cytologic management Histologic management Positivity by Age (UK)

1 Faculty disclosure Cervical Cancer Prevention for Francisco, MD, MPH Associate Professor Obstetrics & Gynecology Mexican American Studies Public Health Francisco, MD, MPH has no financial affiliations to disclose Note: Additional disclosure information is located within the program Objectives Review the epidemiology of related disease in adolescents Discuss screening in this population Understand dthe NIH/ASCCP Guidelines recommendation for Cytologic management Histologic management Positivity by Age (UK) 3% Percentag ge (+) 25% 2% 15% 1% Any High-risk 5% % Peto et al Br. J. Cancer 24:91: Age Group 1

LSIL REGRESSION BY AGE CATEGORY 2 1 2 3 4 Months After Diagnosis 5 6 Moscicki AB, Shafer MA: Normal reproductive development in

41.2 months Winer (23), Am J Epidemiol ence of on Cumulative Incide Infectio Infection From Time of First Sexual Intercourse 2

4 8 12 16 2 24 28 32 36 4 44 48 52 56 From Winer RL, Lee S K, Hughes JP, Adam DE, Kiviat Months NB, Koutsky Since LA.

2 SURVIVAL PLOT FOR TOP 8 TYPES 22 Time to Clearance portion With L-SIL Estimated Prop ESTIMATE OF TIME TO LSIL REGRESSION BY AGE CATEGORY Months After Diagnosis 5 6 Moscicki AB, Shafer MA: Normal reproductive development in the adolescent female. Journal of Adolescent Health Care 1986;7:41S-6 Moscicki. Unpublished data. 25. Adapted from Moscicki et al. Lancet. 24;364: Exposure & Infection in Young Women Follow up study of college women in Seattle N=553, mean=19, cyto, q 4months x 5 yrs Mean f/u 41.2 months Winer (23), Am J Epidemiol ence of on Cumulative Incide Infectio Infection From Time of First Sexual Intercourse Study of female college students (N=63) From Winer RL, Lee S K, Hughes JP, Adam DE, Kiviat Months NB, Koutsky Since LA. First Genital Intercourse human papillomavirus infection: Incidence and risk factors in a cohort of female university students. Am J Epidemiol. 23;157: , by permission of Oxford University Press. What happens to new infections in Adolescents? Adolescent follow up study, Indianapolis 6 adolescents (14 17 years old) followed 26 months Pelvic, 3mo interval 15 wk period of weekly vaginal self collection for Brown (25) J Infect Dis 2

Adolescent Follow up Study Time Point Any HR Enrollment 28% 22% Exit 4% 37% On 2 visits 82% 77% Only 3 subjects had all negative tests* FACTORS CONSISTENTLY REPORTED TO IMPACT NATURAL HISTORY OF /CVX

3 Adolescent Follow up Study Time Point Any HR Enrollment 28% 22% Exit 4% 37% On 2 visits 82% 77% Only 3 subjects had all negative tests* FACTORS CONSISTENTLY REPORTED TO IMPACT NATURAL HISTORY OF /CVX CA Increasing age type (-16) Multiple types? Younger age Smoking? Increasing no. sex partners Chlamydia? Male factor * Nutrients? Smoking? Human leukocyte antigen? Pregnancy/multiparity? Male factor? type NEGATIVE POSITIVE PERSISTENCE > CIN 2/3 Increasing age type (-16), Multiple types? Smoking Multiparity? OC use? Chlamydia? No use of condoms? HLA? Nutrients? Increasing age INVASIVE CANCER Smoking** Multiparity Long-term OC use *no circumcision, increasing number of sex partners, visits to prostitutes, no condom use OC: Oral contraceptives **data from case-control studies HLA: Human leukocyte antigen CIN: Cervical intraepithelial neoplasia Vaccine, Vol 24 Supplement 3, Elsevier Limited. All rights reserved. Chapter 5, Figure 7 Definition of Adolescents: for the Purpose of Cervical CA Screening infection and spontaneous clearance very common after sexual debut Only persistent increases cancer risk Risk declines continuously But guidelines require dichotomization of groups Women younger than 21 years of age should be managed differently. Professional societies recommend initiating Pap testing at or after 21 Recognizes rising cancer risk as women enter their 2s Defining women before this age as adolescent improves congruence AGE-SPECIFIC PREVALENCE AMONG WOMEN WITH NORMAL CYTOLOGY: A META-ANALYSIS OF 78 STUDIES Prevalence % ADJUSTED MODEL UNADJUSTED < > 69 AGE GROUP Reprinted from de Sanjose S. El virus del papiloma humano y cáncer: Epidemiologia y Prevencion. Ed.: S. de Sanjose & A., EMISA, Madrid, 2 Vaccine, Vol 24 Supplement 3, Elsevier Limited. All rights reserved. Chapter 6, Figure 1 Cervical Cancer in US by Age Group yrs.3 per 1, 2-24 yrs 2.6 per 1, yrs 7.8 per 1, 3-34 yrs 11.4 per 1, yrs 14.4 per 1, *SEER all races 3

Screening Young Women Should not be screened unless sexually active for 3 years, or 21 ASC/LSIL rate quite high reflecting high prevalence Cervical cancer extremely rare in adolescents.

of M. Schiffman ASC/LSIL in Adolescents 91% of adolescents with LSIL will regress by 36 months Most CIN 2,3 in adolescents is really CIN 2 Although CIN 3 is found in some adolescents progression to

4 Screening Young Women Should not be screened unless sexually active for 3 years, or 21 ASC/LSIL rate quite high reflecting high prevalence Cervical cancer extremely rare in adolescents. Natural History of Infection & Cervical Cancer Persistence Managing Abnormal Screening Results Normal Cervix Infection Progression Invasion Pre cancer Infection Clearance Regression Cancer Courtesy of M. Schiffman ASC/LSIL in Adolescents 91% of adolescents with LSIL will regress by 36 months Most CIN 2,3 in adolescents is really CIN 2 Although CIN 3 is found in some adolescents progression to ca extremely rare before 2 Most women with CIN3 are picked up during subsequent screening. Moscicki AB et al. Lancet 24;364: ALTS: ASC/LSIL2-year CIN2 risk 11% after normal colp 12% after abn colp/neg bx 13% after CIN1 bx Low risk of CIN2+ means all 3 scenarios should be managed similarly Cox JT et al. AJOG 23;188:

5 Testing in Adolescents 8% test positive for over 2 years, often multiple types Repetitively positive likely represents new incident not persistent disease. Therefore Referral of adolescents based on (non-type specific) positive tests is of dubious value. Follow up with cytology is preferred. Combined cyto/ screening not recommended <3 Brown DR et al. J Infect Dis 25;191: ASC/LSIL in Adolescents F/U with annual cytology recommended. (AII) At the 12 months only HSIL or greater on repeat cytology referred to colposcopy. (AII) At the 24 months follow-up, those with an ASC-US or greater referred to colposcopy. (AII) testing unacceptable (EII) If inadvertently performed, results should not influence management. Wright TC et al. AJOG (4): LSIL in Adolescents: What s New? No initial colposcopy Annual Pap testing No triage or surveillance testing Cyto f/u 2 years unless HSIL at 12 months Colposcopy at 2 years if ASC/LSIL persist Wright TC et al. AJOG (4): HSIL in Adolescents Colposcopy recommended, & see and treat unacceptable (AII) When CIN 2/3 not identified histologically 24 mo obs with colpo/cyto at 6 mo preferred provided the colpo is satisfactory and endocervical sampling is negative. (BIII) After two NILM and no high-grade colpo abnormality routine cytological screening. (BIII) HSIL in Adolescents Diagnostic LEEP recommended If HSIL persists for 24 months(biii) for HSIL when colpo unsatisfactory ECC postive (any grade) (BII) 5

AJOG 27;197(4):346-355 Management of CIN in Adolescents Impact of LEEP & Future Pregnancy Outcomes New guidelines allow for conservative management of possible high grade disease.

6 HSIL in Adolescents: Statement against see and treat Observation of with HSIL now preferred. Treatment reserved for exceptional circumstances Specific recommendations for the subsequent follow-up are provided. Wright TC et al. AJOG 27;197(4): Management of CIN in Adolescents Impact of LEEP & Future Pregnancy Outcomes New guidelines allow for conservative management of possible high grade disease. recommend observation of borderline changes without colposcopy/treatment designed to avoid over-diagnosis/treatment These changes are the result of new studies showing that loop excision adversely impacts pregnancy outcomes Treatment & Pregnancy Outcomes Women with LEEP more likely to have Preterm birth (O.R. 1.7) Low birth weight (O.R. 1.8) Preterm PROM (O.R. 2.7) Similar findings for ckc or laser cone Ablative treatments lack this association Cone height associated with risk Risk increased for CIN pts, regardless of treatment Studies conflicting, absolute risk increase small Kyrgiou M et al. Lancet 26;367:489-98; Bruinsma et al. BJOG 27;114:7-8 CIN1 in Adolescents F/U annual cyto recommended for CIN1. (AII) Follow-up with unacceptable. (EII) At 12 months follow-up, only >HSIL on repeat cyto goes colposcopy. At 24 month follow-up, those with an ASC-US or greater result should be referred to colposcopy. (AII) Wright TC et al. AJOG 27;197(4):

7 CIN1 in Adolescents No treatment of CIN1 Prolonged follow-up with Pap only no No colpo unless HSIL or ASC/LSIL for two years Wright TC et al. AJOG 27;197(4): CIN2/3 Management in Adolescents: Rationale CIN2 and 3 may regress. Regression may occur in 4% of women with CIN2,3 before the age of 3. Risk of cancer in adolescents is very low. CIN2,3 reported commonly as composite diagnosis Management of CIN2/3 in Adolescents: Rationale 18-month natural history of adolescent CIN2/3 65% regression 17% no change 13% progression to CIN3 (no cancer) Ostor Int J Gynecol Pathol 1993;12:186-92; Nygard JF et al Acta Cytol. 26;5: Moore et al, AJOG 27;197:141.e1-141.e6 Adolescent CIN 2/3 Management Treatment or observe for up to 24 months with month intervals, if colpo satisfactory. (BIII) CIN2 specified, observation preferred but treatment acceptable. CIN3 is specified, or colpo unsat treatment recommended. CIN2 and CIN2/3 can be followed for up to 24 months, if colp satisfactory. Wright TC et al. AJOG 27;197(4): Observation of CIN2/3 in Adolescents If the colpo worsens, or HSIL cytology or highgrade colpo lesion persists for one year, repeat biopsy (BIII) Treatment recommended if CIN3 or if CIN2,3 persists 24 months. (BII) After two NILM results, women with normal colpo return to routine cyto screening. (BII) Wright TC et al. AJOG 27;197(4):

Conclusion Cervical cancer screening in women at the lowest risk for disease needs to balance safety and overly aggressive treatment New guidelines based on improved understanding of the

8 Conclusion Cervical cancer screening in women at the lowest risk for disease needs to balance safety and overly aggressive treatment New guidelines based on improved understanding of the disease process and limitations of screening/diagnostics Harmonize screening and management of abnormal cyto/histo Primum non nocere

Case Based Problems. Recommended Guidelines. Workshop: Case Management of Abnormal Pap Smears and Colposcopies. Disclosure

Case Based Problems. Recommended Guidelines. Workshop: Case Management of Abnormal Pap Smears and Colposcopies. Disclosure Disclosure Workshop: Case Management of Abnormal Pap Smears and Colposcopies Rebecca Jackson, MD Associate Professor Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics This