Current guidelines for
Cervical Cancer Screening
Rachael Chambers, DO
May 29, 2015
Objectives
• Review current cervical cancer screening
guidelines
• Discuss role of HPV testing in cervical cancer
screening
• Discuss role of primary HPV testing in cervical
cancer screening
Background
• Initial Bethesda system classification
– revised in 2001
• ASCCP consensus conference 2006
• Updated guidelines in 2008
– Not from a national consensus conference
• 2012 follow up consensus conference
– Data from KPNC, NCI, ALTS
2012 Consensus Conference
• 47 experts
• 23 professional societies
• Goal to provide revised evidence-based
consensus guidelines for managing women with
abnormal cervical cancer screening tests,
cervical intraepithelial neoplasia and
adenocarcinoma in-situ
Major changes 2012 guidelines
• ECC showing CIN 1
– manage as CIN 1
• Repeat unsatisfactory cytology
– Even when HPV results are known
• Negative cytology with absent or insufficient
endocervical cells can be managed without early
repeat
Major changes 2012 guidelines
• Genotyping triages HR HPV positive women to
colposcopy earlier after negative cytology
– Colposcopy indicated for ASCUS +HPV
regardless of genotyping
• HPV negative ASCUS
– Follow up at 3 years with co-testing
– Not sufficient for exiting women from screening at
age 65
Major changes 2012 guidelines
• CIN 2+ follow up is more clearly defined with
incorporation of co-testing
• Women age 21-24
– Conservative management
– Pap only
– Co-test in certain circumstances
• Incorporate co-testing post colposcopy
Guidelines
• Available at:
• www.asccp.org/Portals/9/docs/ASCCP%20Mana
gement%20Guidelines_August%202014.pdf
• App available for iPad, iPhone and Android
Routine Screening
• Cytology every 3 years
• Co-testing every 5 years
– Women age 30-64 only
• Multi-year intervals ok only if risk of developing
CIN 3+ is low
Case 1
•
•
•
•
55 year old G2P2
Menopause at age 52
No history of abnormal pap testing
Pap test with physical shows:
– Insufficient cellularity. HPV co-testing is negative.
• Now what?
Unsatisfactory Cytology
• 1% or less across all preparations
• Decreased with use of liquid based pap
• Most cases now due to insufficient squamous
cells
Case 2
• Same patient as in Case 1
• Now pap test shows normal results, but no
EC/TZ
• HPV remains negative
• Now what?
Cytology NILM but EC/TZ
Absent/Insufficient
• Suggests squamocolumnar junction may not
have been adequately sampled
• Reported rates 10-20%
• More prevalent in older women
• Good specificity and negative predictive value
• HPV testing is independent of TZ sampling
– Adds margin of safety when co-testing is
performed.
Management
• Age 21-29: routine screening
• Age 30-64
– HPV negative: Routine screening
– HPV unknown: Test for HPV or repeat cytology in
3 years
– HPV positive: Cytology +HPV in 1 year or HPV
genotyping
Case 3
•
•
•
•
32 year old G1P0
No previous pap testing available
Here for initial prenatal care
How do we screen her?
Case 3 continued
• Pap test normal
• HPV co-test is positive
• Now what?
Management Negative Cytology,
HPV positive
• Due to increased risk for CIN 3+ if hrHPV
positive guidelines balance risk of observation
vs intervention
• Return for earlier retesting
• HPV genotyping
– Higher risk of CIN 3+ with type 16/18
• Colposcopy if 1 year follow up is ASC or HPV +
or immediately if HPV 16/18 are positive
Case 4
• 30 year old referred to you for management of
ASCUS pap
• What else do you want to know?
• Was she HPV co-tested?
Atypical Squamous Cells of
Undetermined Significance
• Most common cytologic abnormality
• Lowest risk of CIN 3+
– 2/3 are NOT HPV associated
• Women >60 years have higher risk for cervical
cancer even if HPV negative compared to
women with negative co-testing.
ASC-US
• Reflex HPV testing preferred
– Type 16/18 positive women have twice the risk of
CIN 3+ compared to other hrHPV positive women
• HPV negative
– Repeat cotesting in 3 years
• HPV positive
– Colposcopy
– If no CIN co-test at 12 months
ASC-US
• Cytology only
– Repeat cytology in 1 year
– Colposcopy if > ASC
– Routine screening if normal
ASC-US in Special Populations
• Postmenopausal
– Manage the same as general population
• Women age 65 and older
– Repeat screening in 1 year when considering exit
from screening
• Cytology
• Co-testing (preferred)
ASC-US in Special Populations
• Pregnant women
– Identical to nonpregnant women
– Acceptable to defer colposcopy until 6 weeks
postpartum
– ECC is unacceptable
– If no suspected CIN 2+ at initial colposcopy,
follow up postpartum
Case 5
•
•
•
•
21 year old, G0
No previous pap test
Seen for complete physical
Pap test shows LSIL.
• What next?
Young Women
• No screening before age 21
• Routine screening with initial normal pap test is
every 3 years
– Cervical CA risk is low through age 25
– HPV is common
– Most lesions will regress
• Less intensive management
• Encourage HPV vaccination, smoking cessation
Young women
• ASCUS/LSIL Cytology every 12 months
preferred
– HPV reflex is acceptable
• Follow up is repeat cytology if positive
• Routine screening if negative
• Colposcopy only if ASC-H, AGC, HSIL at follow
up
Low-grade Squamous
Intraepithelial Lesions
• ALTS Trial showed natural history to be similar
to ASC-US HPV+
• Women 21-24 have lower risk CIN 3+
• Estimated 77% of LSIL are HPV positive
LSIL Management
• Colposcopy (recommended)
– Manage based on colposcopic findings
• If co-test is negative, repeat co-test in 1 year
– If cytology negative and HPV negative
• Repeat co-testing in 3 years
– If >ASC or HPV positive
• Colposcopy
LSIL Management
• Pregnant women:
– Colposcopy preferred
• ECC unacceptable
• Acceptable to defer until 6 weeks postpartum
– If no CIN 2+, follow up post partum
LSIL Management
• Postmenopausal
–
–
–
–
Obtain HPV test
Repeat cytology at 6 and 12 months
Colposcopy
Repeat cytology in 12 months if HPV negative or
no CIN on colposcopy
– If HPV+ or ASC-US or greater on repeat cytology
perform colposcopy
– Routine screening after 2 negative cytology
Atypical Squamous Cells,
Cannot Exclude High-Grade
Squamous Intraepithelial Lesion
• Higher risk of CIN 3+ compared to ASC-US or
LSIL
– Risk also elevated for women age 21-24, but
overall CIN 3+ risk remains lower than older
women
ASC-H Management
• Colposcopy for all women
• High rate of HPV + makes reflex testing
unsuitable
• 5 year cancer risk among ASC-H, HPV negative
is 2%
High-Grade Squamous
Intraepithelial Lesion
• CIN 2+ identified in 60% of women at
colposcopy
• Consider immediate excision of transformation
zone
• Cervical cancer found in 2% at colposcopy
– Risk rises with age
– Risk modifies with HPV result
• HPV result from co-test may help inform choice
Management HSIL
• Immediate LEEP
• Colposcopy
– Diagnostic excisional procedure recommneded
for inadequate colposcopy
• Except if pregnant
HSIL in Young Women
• Colposcopy
– If no CIN 2+ observe with colposcopy and
cytology at 6 month intervals for 24 months.
– If CIN 2/3 present manage with colposcopy and
biopsy or treat
Atypical Glandular Cells
• Interpretation is poorly reproducible and
uncommon
• Associated with
– Polyps
– Metaplasia
– Neoplasia
• Adenocarcinomas
– Endometrium, cervix, ovary, fallopian tube and
other sites
AGC
• Risk of neoplasia higher if reported as AGC
favor neoplasia or AIS
• Cancer risk is lower in women <35, but risk of
CIN 2+ is higher
• Commonly associated with squamous lesions
including CIN 1
AGC Management
• Colposcopy with ECC
• Do not use HPV testing to triage
• Endometrial sampling is recommended in
women 35+
– Also for women <35 if clinical indictors suggesting
risk for endometrial neoplasia.
• If no CIN 2+ co-test at 12 and 24 months and
routine screening if both are negative.
What’s next?
PRIMARY HPV SCREENING
Primary hrHPV screening
• Rate of hrHPV is common in sexually active
population
• Most infections are transient
• FDA previously approved hrHPV testing
– For triage of ASCUS
– Adjunct to cytology for women age 30+
• April 2014 FDA approved labeling of hrHPV
assay to include primary hrHPV screening in
women 25+
Primary hrHPV screening
• Highly sensitive
• Specificity depends on subsequent evaluation
strategies and screening frequencies
2011 guidelines
• American Cancer Society, American Society for
Colposcopy and Cervical Pathology and
American Society for Clinical Pathology
• “in most clinical settings, women age 30-65
should not be screened with HPV testing alone
as an alternative to co-testing at 5 year intervals
or cytology alone at 3 year intervals”
Consensus panel
• Met via conference call and face to face
• Invited to scientific summary presentation by
Roche Diagnostics of the Addressing the Need
for Advanced HPV Diagnostics (ATHENA) trial
• MEDLINE database review
– 11 papers reviewed in addition to significant
papers published prior to November 2011
Consensus panel: Primary
question
• Is hrHPV testing for primary screening as safe
and effective as cytology-based screening?
• Negative hrHPV provides greater reassurance of
low CIN3+ risk than negative cytology.
– Several large trials have evaluated this
Consensus panel: Primary
question
• Can primary hrHPV screening be considered as
an alternative to current US cervical cancer
screening methods?
• hrHPV can be considered as an alternative to
current cytology-based screening because of
equivalent of superior effectiveness.
Additional questions
• How Should Positive hrHPV be managed?
– Combination of triage of genotyping and reflex
cytology appears to be a reasonable approach
• Based on data from ATHENA and other studies
• What is the Optimal Screening interval?
– No sooner than every 3 years
• Limited data available
Additional questions
• At What Age Should One initiate primary HPV
screening?
– Not before age 25
Additional questions
• How does the performance of primary hrHPV
screening compare to co-testing?
– Most reassurance from co-test comes from the
HPV component.
– Data shows the 3 year risk following HPV
negative test is less than the 5 year risk following
co-testing.
– Primary hrHPV test every 3 years is at least as
effective as 5 year co-testing.
• Currently only 1 hrHPV test is FDA-approved for
primary screening.
• Comparative effectiveness studies are needed
• Look for future updates
Summary
• Cervical cancer screening continues to evolve.
• Trend is toward less invasive methods of
screening and managing.
• hrHPV screening may become the primary
screening tool in the future.
References
•
•
•
•
•
•
•
Massad, et al. 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical
Cancer Screening Tests and Cancer Precursors. Journal of Lower Genital Tract Disease, Volume
17, Number 5, 2013, S1-S27.
Huh , et al. Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer
Screening: Interim Clinical Guidance. Journal of Lower Genital Tract Disease, Volume 19,
Number 2, 2015, 91-96.
Partridge et al. Cervical Cancer Screening: Featured Updates. Journal of the National
Comprehensive Cancer Network. Volume 12, number 3, march 2014, 333-341.
ACOG Practice Bulletin. Management of Abnormal Cervical Cancer Screening Test Results and
Cervical Cancer Precursors. Number 140, Volume 122, No. 6, December 2013, 1338-1367
Saraiya, et al. Evolution of cervical cancer screening and prevention in United States and
Canada: Implications for public health practitioners and clinicians. Preventive Medicine, Volume
57, 2013, 426-433.
Dinkelspiel and Kinney. State of the Science: Cervical cancer screening in transition.
Gynecologic Oncology, 133, 2014, 389-393.
Cannistra and Niolff. Cancer of the Uterine Cervix. The New England Journal of Medicine.
Volume 334, number 16, 1996, 1030-1038.