Objectives
Cervical Cancer Screening:
•Understand the development of the pap test •Review the role of the pap test in cervical cancer screening
An Update for Primary Care
•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 •Early pioneer in sex-determination research •Subject was guinea pigs, especially around ovulation •No menstrual flow for timing
Development of the Pap Test
•Timed ovulation by studying vagina and cervix
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•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
“The first observation of cancer cells in the smear of the uterine cervix was one of the most thrilling experiences of my scientific career” career
••“Human Human Pregnancy Diagnosed by Vaginal Smear”, 1925
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Began a mass screening of all female patients admitted to NY Hospital, 1939
•Occasionally noticed cancerous cells on admission smears
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Historical Perspective
Screening Test for Cervical Cancer
“By use of the vaginal smear a considerable number of asymptomatic and therefore unsuspected cased of uterine malignancy have been discovered, 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”
•“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 p 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
Terminology: The Bethesda System
•Screening Modality
•Normal
•Sample of Cells epithelium of cervix
•Atypical Squamous Cells of Undetermined Significance (ASC-US)
•Fixed on a slide, stained and examined under a microscope
•Atypical Squamous Cells Cannot Exclude High-grade SIL (ASC-H) •Low-grade Squamous Intraepithelial Lesion (LSIL)
•Cell type is or pattern of cells assigned a category or name
•High-grade-Squamous Intraepithelial Lesion (HSIL)
•Estimation of the state of the cervix
•Atypical Gladular Cells (AGC)
•Goal is to find pre-cancer and treat it
•Squamous Cell or Adenocarcinoma
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Etiology and Risk Factors •Early age of intercourse •Number of sexual partners •Smoking •Lower L socieoeconomic i i status t t
Understand the role of HPV in cervical disease
•High-risk male partner •Other STIs
A Pap Test Contains…
Search for Etiology •Sexually Transmitted
•Cells (normal and abnormal)
•Human T Cell Leukemia Virus 1
•Bacteria
•HSV
•Fungus F
H Human P Papilloma ill Vi Virus
•Virus?
Association greater than smoking is to lung cancer
Human Papilloma Virus
Papillomoviruses
•All forms are related
•Non-enveloped doublestranded DNA virus with capsid
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•Genome is circular 7900 nucleotide base pairs
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•Enormous differences in species specificity and oncogenic potential
Genital HPV
Genital HPV
•Differing sequences in the DNA are responsible for the specific ability to infect an anatomic site
High Risk Group 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68
•Genital HPV types infect mucous membranes most efficiently
Low Risk Group
•Genital types divided by frequency of association with malignant tumors
6, 11, 26, 42, 44, 54, 70, 73
Low Risk HPV
High Risk HPV
•Condyloma accuminata
•HPV 16 is universally detected with greatest frequency in cervical cancer
•Low-grade cervical lesions •High-grade cervical lesions •Do D nott iinduce d malignant li t transformation t f ti •Invasive cancer •Unable to integrate well into host genome •Special proteins bind weakly to suppresor genes
•50% of cervical squamous cell carcinoma nd 30% of adenocarcinomas
HPV and Transformation
Infection to Cancer Transient Infection Mildly Abnormal Mucosa
•Viral DNA inserts into the host cell DNA •Causes host cell to make more viral particles and special proteins
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Sexual Activity Normal Mucosa
Persistent Infection High Risk Type
Cervical Dysplasia Severe Abnormal Mucosa
•Special protein bind to host cell DNA causing disruption of growth suppression Cofactors: Smoking, STIs Immune suppression
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Invasive Cervical Cancer
Screening Guidelines
•Within three years of initial coitus (exposure)
Current Guidelines for Cervical Cancer Screening
•May M stop t att age 65 or 70 if no significant i ifi t hi history t off abnormal tests or cervical disease
Screening Special Populations
•Adolescents •Pregnant Women •Women W older ld than th 30
Management of an abnormal pap test
•Post-menopausal Women •Women with compromised immune system
Categories of Test Results
Triage with HPV
•Normal
•ASC-US needs follow up with repeat pap
•Atypical Squamous Cells of Undetermined Significance (ASC-US)
• Persistent ASC-US needs to be evaluated by colposcopy
•Atypical Squamous Cells Cannot Exclude High-grade SIL (ASC-H)
•With LBC a reflexive HPV test can check for high risk types
•Low-grade Squamous Intraepithelial Lesion (LSIL)
•Only patients with high risk types need to be evaluated by colposocopy
•High-grade-Squamous Intraepithelial Lesion (HSIL) •Atypical Gladular Cells (AGC) •Squamous Cell or Adenocarcinoma
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ASC-US
ASC-H
LSIL
HSIL
Atypical Glandular Cells (AGC)
Adolescents and ASC-US/LSIL
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Adolescents and HSIL
Women Over 30
Pregnancy and LSIL
For More Information
Screening and Management Guidelines can be found at:
http://www.asccp.org/consensus/cytological.shtml
Objectives
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•Understand the development of the pap test
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•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
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•Review management of an abnormal pap test
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