Cervical Cancer Screening: An Update for Primary Care

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1 Objectives Cervical Cancer Screening: An Update for Primary Care Understand the development of the pap test Review the role of the pap test in cervical cancer screening Understand the role of HPV in cervical disease Review current guidelines for cervical cancer screening Review management of an abnormal pap test February 1, 2011 Jeffrey Grice, MD, FACOG WAPA 2011 Winter Conference Historical Perspective Development of the Pap Test Early pioneer in sex-determination research Subject was guinea pigs, especially around ovulation No menstrual flow for timing Timed ovulation by studying vagina and cervix Collected cell and placed on slide Distinctive predictable pattern allowed timing of ovulation George Papanicolaou Historical Perspective Historical Perspective Sought a human application for the collected cells Human Pregnancy Diagnosed by Vaginal Smear, 1925 Occasionally noticed cancerous cells on admission smears The first observation of cancer cells in the smear of the uterine cervix was one of the most thrilling experiences of my scientific career Began a mass screening of all female patients admitted to NY Hospital,

2 Historical Perspective By use of the vaginal smear a considerable number of asymptomatic and therefore unsuspected cased of uterine malignancy have been discovered, some fo them in such an early stage of development that they are invisible to the unaided eye or undemonstrable by the biopsy method Screening Test for Cervical Cancer The Diagnostic Value of the Vaginal Smear in Carcinoma of the Uterus, 1941 American Cancer Society Supports Screening Extensive training of pathologists and cytotechnologists begins Ability to screen for dsyplasia Protocols and terminology established and refined 1928 Decrease Incidence in US Role of the pap p test in cervical cancer screening Decrease with advent of pap test The curve has been stable for a couple of decades because of failure to screen a segment of the population The Pap Test Screening Modality Sample of Cells epithelium of cervix Fixed on a slide, stained and examined under a microscope Cell type is or pattern of cells assigned a category or name Estimation of the state of the cervix Goal is to find pre-cancer and treat it Terminology: The Bethesda System Normal Atypical Squamous Cells of Undetermined Significance (ASC-US) Atypical Squamous Cells Cannot Exclude High-grade SIL (ASC-H) Low-grade Squamous Intraepithelial Lesion (LSIL) High-grade-Squamous Intraepithelial Lesion (HSIL) Atypical Gladular Cells (AGC) Squamous Cell or Adenocarcinoma 2

3 Etiology and Risk Factors Early age of intercourse Number of sexual partners Smoking Understand the role of HPV in cervical disease Lower L socieoeconomic i status t High-risk male partner Other STIs A Pap Test Contains Search for Etiology Sexually Transmitted Cells (normal and abnormal) Bacteria FungusF Virus? Human T Cell Leukemia Virus 1 HSV Human Papilloma Virus Association greater than smoking is to lung cancer Human Papilloma Virus Papillomoviruses All forms are related Non-enveloped doublestranded DNA virus with capsid Genome is circular 7900 nucleotide base pairs TIFF (LZW) Similar biologic characteristics Enormous differences in species specificity and oncogenic potential 3

4 Genital HPV Genital HPV Differing sequences in the DNA are responsible for the specific ability to infect an anatomic site Genital HPV types infect mucous membranes most efficiently Genital types divided by frequency of association with malignant tumors High Risk Group 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 Low Risk Group 6, 11, 26, 42, 44, 54, 70, 73 Low Risk HPV High Risk HPV Condyloma accuminata Low-grade cervical lesions Do D not induce malignant transformation ti Unable to integrate well into host genome Special proteins bind weakly to suppresor genes HPV 16 is universally detected with greatest frequency in cervical cancer High-grade cervical lesions Invasive cancer 50% of cervical squamous cell carcinoma nd 30% of adenocarcinomas HPV and Transformation Infection to Cancer Viral DNA inserts into the host cell DNA Transient Infection Mildly Abnormal Mucosa Causes host cell to make more viral particles and special proteins Special protein bind to host cell DNA causing disruption of growth suppression Sexual Activity Normal Mucosa Persistent Infection High Risk Type Cervical Dysplasia Severe Abnormal Mucosa Invasive Cervical Cancer Cofactors: Smoking, STIs Immune suppression 4

5 Screening Guidelines Current Guidelines for Cervical Cancer Screening Within three years of initial coitus (exposure) May M stop at age 65 or 70 if no significant ifi history of abnormal tests or cervical disease Screening Special Populations Adolescents Pregnant Women Women W older than 30 Post-menopausal Women Women with compromised immune system Management of an abnormal pap test Categories of Test Results Normal Atypical Squamous Cells of Undetermined Significance (ASC-US) Atypical Squamous Cells Cannot Exclude High-grade SIL (ASC-H) Low-grade Squamous Intraepithelial Lesion (LSIL) High-grade-Squamous Intraepithelial Lesion (HSIL) Atypical Gladular Cells (AGC) Triage with HPV ASC-US needs follow up with repeat pap Persistent ASC-US needs to be evaluated by colposcopy With LBC a reflexive HPV test can check for high risk types Only patients with high risk types need to be evaluated by colposocopy Squamous Cell or Adenocarcinoma 5

6 ASC-US ASC-H LSIL HSIL Atypical Glandular Cells (AGC) Adolescents and ASC-US/LSIL 6

7 Adolescents and HSIL Women Over 30 Pregnancy and LSIL For More Information Screening and Management Guidelines can be found at: Objectives Understand the development of the pap test Review the role of the pap test in cervical cancer screening Understand the role of HPV in cervical disease Review current guidelines for cervical cancer screening Review management of an abnormal pap test 7