Faculty Pap Smear Guidelines: Family Planning Update 2008 Seshu P. Sarma, MD, FAAP Part Two Emory University Regional Training Center Atlanta, Georgia Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division Objectives Objectives Discuss pap smear reporting Discuss management strategies for various squamous and gladular cell Describe the Bethesda system 2006 abnormalities Discuss management of unsatisfactory smears and smears with no T zone Discuss treatment modalities for CIN component Cervical Cancer Pap Smear Reporting Pap smear screening resulted in Pap system of reporting dramatic reduction in cervical cancer − Bethesda 1988 system The value of accurate screening can be − Bethesda 1991 system reduced by loss to follow-up or under- treatment of significant lesions − Bethesda 2001 system − Bethesda 2006 system 1 Pap Reporting WHO Reporting Class 1 − Normal CIN 1 Class 2 − Mild dysplasia − Atypia, inflammation, reactive change CIN 2 Class 3 − Dysplasia − Moderate dysplasia Mild, moderate and severe CIN 3 Class 4 − Severe dysplasia − Carcinoma in situ − Carcinoma in situ Class 5 − Invasive cancer Bethesda System Bethesda 2006 146 experts Bethesda 1988 29 organizations Bethesda 2001 Met September 18-19, 2006 in Bethesda 2006 Bethesda, MD Developed revised, evidence based consensus guidelines for management of abnormal pap smears Bethesda 2006 Bethesda 2006 ASCUS Recommendations for HSIL and AGC LGSIL underwent only minor changes − Management unchanged for the above 2 categories except for More emphasis placed on immediate screen and treat for HSIL lesions adolescents − Cytologic follow-up for 2 years approved for adolescents 2 Bethesda 2006 Bethesda 2006 HPV testing was incorporated into the The 2004 interim guidance for HPV management of AGC after initial testing as a adjunct to cervical cytology evaluation with colposcopy and for screening in women 30 years of age endometrial sampling or older was formally approved Adequate Specimen Adequacy of Specimen Conventional Smear: − 8,000-12,000 well visualized cells Satisfactory specimen contains should be seen − 10 well preserved endocervical cells Liquid-based Pap: or 5,000 well visualized cells should be − 10 squamous metaplastic cells seen − − Epithelial cells may be obscured by inflammation − If >75% of cells are obscured, it is considered unsatisfactory Transformation Zone No T Zone Components Not Present • Repeat testing is recommended for • If Pap is otherwise normal, no higher women at higher risk of neoplasia risk of subsequent detection of high such as: grade SIL − Immunocompromised • Most women without an endocervical − HPV + or transformation zone component can − previous abnormal pap smears be re-screened in 12 months − Inability to visualize the cervix − Insufficient previous screening 3 Unsatisfactory Pap Smears Abnormal Pap Smears 50-60 million pap tests per year in US Pap smears that are unsatisfactory need to be repeated in 2-4 months 3.5 million are classified as abnormal and require some form of medical If three consecutive specimens are follow-up unsatisfactory, colposcopy is recommended 10,000 new cases of cervical cancer − Histologic abnormalities were found seen each year in the US in 16% of this population 4,000 deaths from cervical cancer Abnormal Pap and Inconclusive Pap Smears Cervical Cancer Almost 2 million Pap smears each year Determining which women with are classified as “inconclusive” abnormal Pap tests are at risk of significant cervical disease and treating − ASC-US, ASC-H and LSIL them presents a: Most of them have no detectable − major public health challenge problem multibillion dollar cost to our − Less than one fifth of these women healthcare system have a significant precancerous lesion Inconclusive Pap Smears Abnormal Pap Smears Effective cervical cancer prevention Although these changes are mild, they requires may result in: − Anxiety − Recognition and treatment of the precursors of invasive cancer − Unnecessary medical procedures − Extra costs to healthcare system The 2001 Bethesda System of nomenclature describes the categories of epithelial cell abnormalities seen on pap smears 4 2001 Bethesda System 2001 Bethesda System Squamous Cell: Squamous Cell: Atypical Sqaumous Cells − − High-grade squamous intraepithelial ASC-US (undetermined significance) lesions ASC-H ( can not exclude HSIL) Moderate and severe dysplasia and − Low-grade squamous intraepithelial carcinoma-in-situ (CIN II and CIN III) lesions Mild dysplasia − Squamous cell carcinoma HPV changes 2001 Bethesda System 2001 Bethesda System Glandular Cell: Glandular Cell: Atypical glandular cells − Atypical glandular cells (AGC) − Favor neoplasia Endocervical Specify endocervical Endometrial Not otherwise specified (NOS) Not otherwise specified (NOS) − Endocervical adnocarcinoma in situ (AIS) − Adenocarcinoma Precancerous Precursors HPV and Abnormal Paps CIN 2, CIN 3, adeno-carcinoma in situ The presence of HPV is a marker for the (AIS) are collectively referred to as risk of diagnosis of CIN2/3+ CIN2/3+ Only 1 in 10 to 1 in 30 HPV infections Cancer precursors include: are associated with abnormal cervical − CIN 3, AIS and to a lesser extent cytology CIN 2 Even a smaller proportion are associated with CIN2/3/+ 5 HPV HPV HPV can express as CIN within months Among women with negative cytology and a positive HPV test result, only 15% after infection will have abnormal cytology results However, the time course from CIN 3 to within 5 years invasive cancer averages between 8.1 and 12.6 years CIN Regression CIN 1 CIN 1 is the histologic appearance of Regression for CIN cells producing HPV − 60% for CIN 1 and 40% for CIN 2 The goals of cervical cancer screening: − Not to prevent CIN − But to prevent and treat Early invasive cervical cancer Reduce mortality Management of Abnormal Pap Atypical Squamous Cells Atypical Squamous Cells: Options include: − Immediate colposcopy The risk of cancer and CIN 2/3+ is low − 0.1-0.2% for cancer Provides rapid diagnosis but expensive − 6.4-11.9% for CIN2/3+ − HPV DNA testing triage − Repeat cytology at 6 and 12 months 6 HPV Testing ASCUS (HPV+) in Adolescents Hybrid Capture DNA 2 assay for 13 The risk of invasive cancer approaches zero in adolescents oncogenic HPBV sub types HPV infections are common and self Performed on the liquid based pap limiting in adolescents specimen Colposcopic evaluation is not necessary Usually done within 3 weeks of Can be monitored with pap smears at 6 obtaining the specimen and 12 months Adolescents ASCUS and LSIL in Adolescents Recommendations are similar for ASC and LSIL in adolescent girls Follow-up with cytology or HPV for up to 2 years is reasonable according to LSIL represents HPV infection and Bethesda 2006 guidelines most adolescents clear HPV and LSIL Follow-up Pap at 6 and 12 months is adequate LSIL LSIL More frequent in younger populations The risk of CIN 2/3+ at initial colposcopy following an LSIL is with larger number of recent partners between 15% and 30% Represents the appearance of cells that Colposcopy is recommended for these women are actively engaged in HPV replication For adolescents with LSIL, follow-up HPV testing is of limited value with Pap at 6 and 12 months is reasonable 7 LSIL in Adolescents LSIL in Postmenopausal Women Follow-up at 6 and 12 months Options include: − Those with HSIL need colposcopy − Reflex HPV DNA testing Follow-up at 24 months − Repeat cytology at 6 and 12 months − Those with ASCUS or greater need − Colposcopy colposcopy 2006 Bethesda guidelines Bethesda 2006 guidelines ASC-H HSIL Among women with HSIL cytology Atypical squamous cells-cannot results: exclude HSIL (ASC-H); − CIN 2 and CIN 3 have been reported − Includes 5-10% of ASC Pap smears in 70% or more cases − Invasive cancer is seen in 1-2% of − CIN2/3+ seen in 24-94% of such cases cases − Colposcopy with endocervical − Immediate colposcopic intervention evaluation should be done is necessary − Entire vagina should be examined − See and treat approach can be − HPV testing is not cost effective followed if lesion seen AGC AGC Atypical Glandular Cells: Source of the lesion − Histological correlation: − Cervix − 9-38% of women with AGC have − Endocervix significant neoplasia − Endometrium − 3-17% have cancer − CIN is the most common lesion associated with AGC 8 AGC AGC Evaluation includes: When evaluation is negative and − Colposcopy histology is negative, follow-up includes: − Endocervical curettage − AGC favor neoplasia: excision is − Endometrial sampling warranted With abnormal endometrial cells Cold knife cone is a good choice Women >35 years of age − AGC and AGC NOS Younger women with abnormal Pap and ECC every 6 months until bleeding, morbid obesity and 4 consecutive negative smears are oligomenorrhea obtained How Should CIN 1 Be CIN 2 and 3 Managed? CIN 2 and 3 are recognized potential Depends on the preferences of the cancer precursors − Physician and the patient − Although CIN2 is associated with − For most young women, observation significant spontaneous regression seems appropriate − 40% of CIN 2 cases regress over 2 − Follow-up with pap smear every 6 years months X 2 Immediate treatment of CIN2 and CIN 3 with excision or ablation is Colposcopy for an ASC or higher recommended in non-pregnant patients or a positive HPV at 12 months CIN 2 in Adolescents Management of AIS Care of the adolescent with CIN 2 may Cold-knife conization is recommended