Abnormal Pap Smears: Faculty Management and Seshu P. Sarma, M.D. Counseling Emory Regional Training Center Satellite Conference and Live Webcast Atlanta, Georgia Wednesday, February 14, 2007 2:00 - 4:00 p.m. (Central Time) Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division Program Objectives Program Objectives • Discuss the epidemiology and • Describe Bethesda 2001 Pap etiology of cervical precancerous terminology. and cancerous disease. • Describe the natural course of HPV • Discuss management guidelines for infection and its role in the development of cervical cancer. various abnormal Pap smear findings. • Discuss new Pap smear recommendations and the rationale behind the new changes. Cervical Cancer Etiology of Cervical Cancer • Incidence of Cervical Cancer: • Infection with high risk HPV – 9.2 per 100,000 (age-adjusted for the US population) in 2000 – 16,18,31,33,35,39,45,51,52,56,58,59 and 68 • Cervical cancer incidence has decreased by 77.7% from 1950 to – Mostly 16,18,45 and 31 2001 • Mortality reduced by as much as 70% – Due to pap smear screening 1 HPV Infection HPV and Cervical Cancer • The prevalence of genital HPV • HPV infections resolve infection spontaneously within 1-2 years. • Persistent infection with High Risk – Highest among sexually active HPV infection is a prerequisite for teens and women in their 20s the development of cervical cancer. • Although HPV infection is necessary – Decreases after age 30 for the development of cervical cancer, majority of women who are infected with HPV do not develop cervical cancer. Risk Factors for Methods of Testing Cervical Cancer • Conventional Method: • Infection with high-risk HPV – Glass slide, wooden spatula and • Smoking cytobrush • Immunosuppression • Liquid Based Method: • Multiple sex partners • Young age at first pregnancy – Cervex brush or broom • Low socioeconomic status – Plastic spatula and cytobrush • Long term oral contraceptive use Pap Screening Liquid Based Pap Smears • Conventional Pap smear is • Shorge et al reported that ThinPrep associated with a high rate of false- yielded a higher pickup of negative results. – Atypical glandular cells of undetermined significance (AGUS) • The use of liquid based Pap testing has decreased the incidence of false- – Adenocarcinoma negative Pap results. – 0.17% of LBP vs 0.09 of conventional 2 Liquid Based Paps Smears HPV Vaccination • In addition, the sensitivity of AGUS • In June 2006, the first HPV vaccine, and adenocarcinoma was found to Gardasil was introduced be significantly greater with the liquid-based test – Effective against types 6 and 11 which cause genital warts – 72.0% with LBP vs 41.5% with – 16 and 18 that are associated with conventional cervical cancer Gardasil Gardasil • The quadrivalent vaccine • Recently, the American College of Obstetrics and Gynecology – Approved by the US FDA for administration to females between published its recommendations: 9 and 26 years of age – Pap test prior to vaccination – Can be given even if infected with HPV – Continue Pap after vaccination – Given as 0.5 ml dose initially, at 2 months and 6 months Barriers to Vaccination HPV Vaccine • Cost • Protection against HPV 16 and 18 only. • Potential for side effects • It is unknown how long the immunity lasts. • Parents’ acceptance of the concept • Other oncogenic subtypes account of vaccinating their preadolescent for 30% of cervical cancers. and adolescent daughters against a • All these are important reasons to STD continue screening for cervical cancer. 3 Computer-Assisted Screening Focal Point Slide Profiler • CAS with an automated microscope • FPSP works with image analysis was developed to prescreen slides and identify those that contain cells software that makes algorithmic of interest. judgments about whether a slide • Two systems have been approved by the FDA for use with liquid based specimen is normal or abnormal. Pap smears: – Thin Prep Imaging System (TPIS). – Focal Point Slide Profiler (FPSP). Thin Prep Image System New Pap Guidelines • TPIS scans slides and identifies cells • American Cancer Society proposed of interest. new Pap smear screening • TPIS imager scans each slide and recommendations in 2002 which identifies 22 fields that contain cells were later endorsed by United States of interest. Preventive Services Task Force and The cytotechnologist then reviews • American College of Obstetrics and those 22 fields using an automated microscope and reports the results. Gynecology. New Pap Guidelines New Pap Guidelines • Begin screening approximately 3 • Consider discontinuing Pap after age years after the 1st vaginal 65 to 70 in well-screened women intercourse or at age 21 whichever comes first – With no history of significant • Test every 1 to 2 years until age 30 dysplasia • Every 2 years with liquid-based Pap (ACS) – Age 65 according to USPSTF and • Test every 2 to 3 years after age 30 – In well screened women with 70 according to ACS negative Pap 4 New Pap Guidelines New Pap Recommendations • Discontinue Pap testing in women • Continue annual Pap screening in women with no cervix: whose uterus and cervix have been – History of cervical removed for benign conditions with cancer/precancer no history of high-grade cervical – In utero exposure to dysplasia or cancer. diethylstilbestrol – Immunocompromised women • HIV positive individuals New Pap Guidelines New Pap Guidelines ACS USPSTF ACOG Screening Conventional or Conventional Conventional or ACS USPSTF ACOG Method liquid liquid Termination Age 70 if Age 65 if Same as of uterus recent ACS Initial 3 years after the Same as ACS Same as ACS screening onset of vaginal screening intact, three screening Recommen- intercourse or consecutive was dations no later than 21 negative adequate years Paps and with Screening Annual with At least Annual no normal Pap interval conventional every 3 years screening before abnormal smears pap or every 2 age 30 and then tests in the years with every 2-3 years if last 10 liquid based 3 consecutive years pap until age 30 tests are negative The Main Questions The Main Questions • Why wait three years after first • What is the role of HPV DNA testing? intercourse for the first pap test? • How should we deal with abnormal results? • Why is the age 21 the “default” age • How should we counsel the for first pap test? patients? • What is the harm in continuing Pap • What are the risks and costs of tests in all women? screening every two to three years in • Will women return for annual exams well-screened women over age 30? as we advise, if we change their Pap Over age 65? routine? 5 Rationale Yearly Pap Smears • Why wait three years after first • The yearly Pap test was advocated intercourse for the 1st pap test? long before data suggested one • Why is the default age 21 for the 1st interval might be better than another. pap test? Why Wait Three Years After Rationale Intercourse? • Cervical cancer develops only after • The goal of Pap smear screening is persistent HPV infection, many years to diagnose and treat precancerous lesions and prevent cancerous from the initial infection. progression. • HPV infections in young women are • A three year delay is highly unlikely to compromise timely diagnosis of usually transient. high grade lesions. • Up to 90% of young women who test • It does allow discovery and eradication of dysplastic changes positive for HPV DNA will revert to long before they become malignant. negative within 2 years. Problems of Screening Early STD Screening and • Squamous cancer of the cervix is Contraception exceedingly rare under age 21. • Delaying Pap by three years in sexually active young women does • HPV infections are exceedingly common in women under age 21. not mean that these women do not need routine gynecologic care. • Diagnosis of self limited HPV infections and transient low grade • They still need dysplastic lesions would lead to – STD screening and counseling. unnecessary repeat Pap smears and/or colposcopies. – Contraceptive counseling. 6 Why Is Age 21 the “Default” Aggressive Screening Until for First Pap? Age 30 • Incidence of High Grade SIL • Screening increases with age. – Every year with conventional Pap • Cervical Cancer is rare in teenagers smears and young women. – Every two years with liquid based • Cytology screening starting at age 21 Pap smears would capture most women at risk. • According to ACS guidelines • A 21 year old who has never had • According to ACOG yearly vaginal intercourse does not need to screening regardless of the be screened for cervical cancer. method is recommended Rationale Pap Screening: Ages 30-65 • Frequent screening until age 30 • Research indicates that it is allows us to identify and treat young reasonable to reduce the screening women with histologic cervical interval from every year to every two intraepithelial neoplasia (CIN II and to three years in previously well- CIN III or worse) which may progress screened women over age 30. to cancer. Rationale Pap Screening: Ages 30-65 • These women have the protection • Both ACOG and ACS recommend offered by frequent pap tests during annual screening regardless of age if following risk factors are present the 20s. – History of cervical cancer/precancer • By the time most women reach their – Immunocompromise (HIV) 30s, the area of active squamous – DES exposure metaplasia which serves as the – Those not screened well under age 30 should have at least three substrate for cervical neoplasia is negative Pap smears reduced. 7 Screening Interval Studies How Many Cancers Will • Frequent screening would detect We Miss? very few additional cancers at an • In a theoretical cohort of 100,000 exceedingly high cost. women who had at least three consecutive negative pap tests, • We can confidently counsel patients screening at one year rather than that a previously well-screened three year intervals would uncover woman over age 30 who has no three additional cancers in women history of dysplasia has an aged 30-44, a single additional exceedingly small risk of cervical cancer in women aged 45-59 and no cancer, whether her next Pap test is additional cancers in women 60-64 1, 2 or 3 years after her last.