Cervical Cancer Screening and Prevention

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Cervical Cancer Screening and Prevention

• Teresa Bryan, M.D
• Associate Professor of Medicine
• GIM Noon Conference
• October 23, 2007

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Objectives

• Review cervical cancer screening guidelines
• Discuss methods available for screening
• Discuss management and f/u for cytologic results

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HPV and Cervical Cancer
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Abnormal Pap test How common is it?
12,200 cancers
300,000 HSIL
1.25 million LSIL
2-3 million ASC
50-60 million women screened
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What is the natural history of HPV infection?
Disease Progression
Normal
Low-Grade SIL
High-Grade SIL
Invasive Cancer
Local
Disease Regression
Regional
Distant
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Cervical Intraephithelial Neoplasia Grading
Scheme for Dysplasia of the Cervix
CIN-3
CIN-2
CIN-1
CIN-1 Dysplastic cells occupy lower 1/3 of
mucosa CIN-2 Dysplastic cells occupy lower
2/3 of mucosa CIN-3 Dysplastic cells extend
into upper 1/3 of mucosa
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Dysplasia Natural History
Ostor AG. Int J Gyn Path. 1993
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Cervical Cancer Stats

• Progression to invasive cancer over 24 months
• LSIL O.15
• HSIL 1.44
• 50 of pts with cancer never received screening
• Additional 10 not screened within 5 yrs of
  diagnosis
• Incidence of CIN is highest b/w age 20-30
• HSIL is rare in previously screened gt65yrs

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GuidelinesWhen to initiate screening?
ACS USPSTF ACOG 3 yrs after onset 3 yrs
after onset 3 yrs after onset of intercourse of
intercourse of intercourse No later than No
later than No later than Age 21 age 21 age
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GuidelinesScreening Interval

• American Cancer Society
• Q 2 years until age 30 with liquid pap
• Annually until age 30 with conventional pap
• Q 2-3 years age 30 if 3 consecutive normals
• USPSTF
• Q 3 years any age
• ACOG
• Annual screening lt 30
• Q 2-3 30 if 3 neg smears

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Exceptions

• In utero DES exposure
• Immunocompromised
• HIV Q 6 months then annually
• H/O CIN II/III or cancer
• Obscured or unsatisfactory cells
• H/O other HPV-related genital tract lesion such
  as VIN 2/3.

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Negative Smears Predict Low Risk(18 month f/u)
Saslow et. Al CA Cancer J Clin 2002 52342
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Cervical Cancer Risk over 3 Years in Women with
3 Negative Smears
N Engl J Med 2003 Oct 16349(16)1501-9.
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Discontinuing Screening

• American Cancer Society
• Age 70 if 3 consecutive satisfactory neg results,
  no abnormal within prior 10 years, no DES, or
  immunocomp
• USPSTF
• Age 65 if recent normal smears and no increase
  risk
• American Geriatrics Society
• Age 70 if prior screening
• ACOG
• Individual annual assessment risk factors and
  exam
• Continue annual exam

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Screening After Total Hysterectomy

• Invasive cervical cancer freq monitoring
  initially, then annually
• CIN II/III annual cytology of vaginal cuff x 3
• DES Exposure in utero annual screening
• Benign conditions
• Not recommended
• Unknown
• annual screening x 3, then d/c

ACS, ACOG
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Screening for cervical cancer Will women accept
less?

• Telephone survey 360 women age 40
• 43 had heard recommendations regarding less
  frequent screening.
• Half believed based on cost
• 69 still desired annual screening
• 35 felt they would eventually d/c paps

Am J Med 2005 118(2)151-8
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HPV DNA TestingScreening

• Should not be used for screening under age 30.
• Detection CIN 2 or greater gt age 35
• HPV 95 sensitivity, 93 specificity
• Pap 60 sensitivity, 97 specificity
• HPV and cytol combined 99-100 sens.
• Alternative approach HPV with cytol triage
• J Cancer 2006191095-101

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HPV DNA vs Pap Screening for Cervical Cancer
Canadian Cervical Cancer Screening Trial
NEJM 20073571579-88
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HPV and Pap to Screen for Cervical Cancer

• RCCT 12,527 swedish women 32-38 years
• Pap alone vs Pap plus HPV
• 51 more women with CIN 2 or greater in combo
  group ? treated
• Combo group had 42 less lesions on f/u.

NEJM 20073571589-97
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Combined Testing gt Age 30Endorsed by ACOG, ASCCP
Amer J Obsterics Gynecol Oct 2007
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Reviewing Pap Smear Results

• American Society for Colposcopy and Cervical
  Pathology
• ASCCP
• Patient Management Guidelines
• www.asccp.org
• American J Obstetrics and Gynecology October 2007

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Unsatisfactory Specimen Adequacy

• Scanty cellular material
• Obscured by blood or inflammation
• Attempt to treat inflammatory process
• Repeat 2-4 months

ASCCP Patient Management Guidelines. J Lower
Genital Tract Dis 2002 6195
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Endocervical Cells Not Present

• Follow-up controversial
• Most OK to repeat 12 months
• Repeat 6 months if
• Prior ASCUS or worse
• Prior glandular abnormality
• HPV positive
• Immunosuppressed
• Endocervical canal not visualized
• Lack of prior screening

ASCCP Patient Management Guidelines. J Lower
Genital Tract Dis 2002 6195
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Epithelial Cell Abnormality

• Squamous
• Atypical Squamous Cells (ASC)
• Undetermined significance (ASCUS)
• Suspicious for HSIL (ASC-H)
• Low-grade squamous intraepithelial lesion (LSIL)
• High-grade squamous intraepithelial lesion (HSIL)
• Squamous cell carcinoma
• Glandular
• Atypical glandular cell
• Endocervical adenocarcinoma in situ (AIS)
• Adenocarcinoma

Bethesda 2001 Classification
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Atypical Squamous Cells

• ASCUS
• Undetermined significance
• 10-20 chance of CIN2/3
• Options
• HPV reflex
• Colposcopy
• Repeat 6 months
• ASC-H
• Cannot rule out high grade intraepithelial lesion
  
• 24-94 chance of CIN2/3
• Refer for colposcopy

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ASCUS TriageReflex HPV
JAMA. 19992811605-1610
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ASCUS-HPV PositiveColposcopy Negative

• HPV testing at 12 months OR
• 2 repeat cytology exams _at_ 6 months intervals
• Repeat colpo if ASCUS or greater

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Special PopulationsASCUS

• Adolescents with ASCUS
• f/u with annual cytology
• At 12 month- only HSIL refer to colposcopy
• At 24 month-ASCUS or greater refer to colposcopy
• HPV testing unacceptable
• HIV with ASCUS
• Same as general population

Amer J OB Gyn October 2007
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LSIL

• 50-80 of LSIL will regress in adult women 1
• Refer for colposcopy unless special population
• Risk of CIN 2 or greater at initial eval 12-16
• F/U colpo negative
• HPV 12 months OR
• Repeat cytology 6 months intervals x 2

1. Obstet Gynecol 198667665-69
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Special PopulationsLSIL Amer J OB Gyn October
2007

• Adolescents
• 90 LSIL will regress in adolescent women 1
• F/U with annual cytology
• At 12 month- only HSIL refer to colposcopy
• At 24 month-ASCUS or greater refer to colposcopy
• HPV testing unacceptable
• Postmenopausal options
• Repeat cytology 6 and 12 months
• Reflex HPV DNA Testing
• Colposcopy

1. Obstet Gynecol 1983 61609-614
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HSIL

• 53-66 with CIN 2 or greater at initial
  colposcopy
• 2 with invasive cancer
• Management
• Immediate loop electrosurgical excision or
• Colpo with endocervical assessment
• Repeat colpo and cytology 6 months if initial
  neg,
• Diagnostic excisional bx if repeat HSIL
• Adolescents
• Colposcopy recommended
• If negative
• Colpo and cytology q 6 months x 24 months
• If persists, excisional bx recommended

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Glandular Cell Abnormalities

• Atypical Glandular cell (AGC)
• 9-38 associated with neoplasia
• Refer for colploscopy, endocervical curettage
• Endometrial biopsy if gt 35
• HPV testing in addition to above
• Endocervical adenocarcinoma in situ (AIS)
• Adenocarcinoma

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Benign Endometrial Cell

• New Bethesda System reports benign endometrial
  cells if age gt 40.
• 12 all paps
• lt 2 women over 40
• Patients with pathology usually had sx that would
  lead to w/u 1,2
• More concerning in post-menopausal women. 1
• After total hysterectomy, no need for w/u

• Am J Clin Pathol.  2005 123 (4) 571-575.
• Cancer. 2006 Feb 25 108(1) 39-44

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Benign Endometrial Cells

• Consider evaluation if
• Abnormal bleeding/anovulation
• FH ovarian, breast, endometrial or colon cancer
• Unopposed estrogen use
• H/O endometrial hyperplasia
• Tamoxifen use
• Postmenopausal

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Trichomonas

• Asymptomatic trich infection detected on liquid
  based pap should be treated
• Perform broader STD screening
• Conventional Paps have higher false positive
  rate, need clinical correlation

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Trichomonas Detection
Am J Obstet Gynecol 2003 188354-356
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Hyperkeratosis

• Not a marker of significant CIN
• Possibly related to infection or trauma
• Repeat 6-12 months

Am J Obstet Gynecol 2002 187997
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Summary

• Start screening 3 years after onset of sexual
  activity or age 21
• Consider lengthening interval up to 3 years in
  women 30 if 3 consecutive normal paps and no
  increased risk factors.
• Age 65 70 is an acceptable age to stop
  screening if normal prior screening and without
  risk factors.
• Management guidelines for pap reports at ASCCP.ORG

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Pap Smear Screening

• 70-80 sensitive for high grade CIN1
• Liquid paps higher detection rate of
  LSIL/ASCUS/AGUS
• Liquid paps with higher number of satisfactory
  specimens

1. www.ahrq.gov/clinic/serfiles.htm.
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Rationale

• Within 3 years of normal pap, severe cytologic
  abnormalities are uncommon.
• 3 year prevalence age 30-64 with 3 neg paps
• CIN 2 .028
• CIN 3 .019
• None with invasive cervical cancer
• Estimated excess risk of 3/100,000 in women 30
  years of age

N Engl J Med 2003 Oct 16349(16)1501-9.