Transcript Successful Cervical Cancer Prevention - Dana

Sarah Feldman MD MPH
Co-Director Ambulatory Gynecologic Oncology
Brigham & Women’s Hospital
Dana Farber Cancer Institute
Lowell Cancer Center
Associate Professor
Harvard Medical School
I, Sarah Feldman. have been asked to disclose any significant
relationships with commercial entities that are either providing
financial support for this program or whose products or services
are mentioned during my presentations.
I have no relationships to disclose.
Requires a programmatic approach including:
 primary vaccination
 screening
 active management of abnormalities to
prevent progression
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There are still 12,360 women diagnosed in
the US annually with cervical cancer, and
4,020 deaths
The 5 year survival of this preventable
disease is 67.9%
We have to do better…
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Evidence Based
Logical, simple to understand and clearly
written
Clearly address areas of patient and provider
confusion
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<21 No screening
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21-29 Pap q 3 years
regardless of sexual activity(no HPV screening)
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30- 65 Pap alone q 3 years or Cotesting/Pap with HPV q 5 years
if both results negative, and normal and negative screens
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age 65 Stop screening if adequate screening
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Defined as 3 neg Paps within prior 10 years or 2 neg cotests within 10 years
Poorly screened women still need to be screened in this age group.
S/p hyst with cervix removed & normal screening history No screening
Any abnormal findings require more aggressive evaluation and follow up as per
the new management guidelines
Excluded “high risk patients”
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ASCCP excluded
ACOG: annual screening for
immunosuppressed, DES unclear
NCCN: HIV, solid organ transplant, or long
term steroid use, DES
USPTF: excluded
AMA: not addressed
WHO: HIV, prior treatment for dysplasia
ACP: Excluded
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Management of Abnormal Pap Smears
(cytology)
Management of Colposcopy Biopsies
(histology)
Follow up after treatment (excision, ablation)
2013 Management Guidelines
Very complicated and difficult to follow
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30 pages long
12 algorithms
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7 for pap smear follow up
5 for colposcopy finding follow up
Unclear which are evidence based and which
are only expert opinion
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Review data:
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HIV positive
Immunosuppressed
Patients with abnormal or inadequate prior
screening histories
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Onset of screening within 1 year of sexual activity
or by age 21; pap q 6 months x2
If normal results-> annual cytology and pelvic
exam, including vulva, anus , cervix and vagina
All women with abnormal test results need
evaluation and more frequent follow up
Status of disease (poor CD4 counts or expected life
expectancy less than 2 years) may alter
recommendation
New guidelines expected soon that may lengthen the
interval for women with all normal results
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Definition of “immunocompromised” varies
May include various rheumatologic diseases, organ
transplants or women on immunosuppressive medications
Increased rates of vulvar (greatest relative increase), vaginal
and cervical cancer relative to immunocompetent women—
need annual pelvic exam including the cervix, vagina, vulva
and anal areas
Increased rates of LSIL abnormalities
Increased rates of cervical HSIL/cancer were generally
modest
Do thorough pelvic exam, and make sure
immunosuppressed patients at a minimum adhere to
standard screening schedules. Consider more frequent
screening for severely immunosuppressed patients.
Evaluate and treat all abnormal results
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Information mostly derived from Kaiser’s large
dataset
Health system with excellent tracking, insurance,
systems to bring patients back for appropriate
testing and management
Data based on earlier screening practices with
more frequent evaluation and more aggressive
management
true rates of cancer or pre-cancer with the current
guidelines cannot be assessed (since patients are
not being detected and treated as often)
May not be generalizable to all settings
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Kaiser data
>30 year old women, tested positive for HPV
Past positive HPV test OR abnormal Pap -significantly higher risk
CIN2+ than newly acquired infection
unknown prior screening history
for ASCUS /HPV+ women with unknown screening history:
-the 4 year cumulative risk of CIN2 was 23 % and of CIN3 was 13%
-similar to women known to have had known prior abnormal results
THUS KNOWLEDGE OF THE PAST SCREENING AND RESULT
HISTORY MATTERS
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Kaiser women >25 years old
Screening results antecedent to colposcopy affected 5 year risk of
CIN2
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Pap
cytology
Colposcopy
histology
5 year risk
of CIN2+
ASCUS/LSI
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CIN1 or less
10 %
ASC-H
CIN1 or less
16%
HSIL
CIN1 or less
24%
No group had sufficiently low risk to return to
“routine” screening
If prior Pap showed ASC-H or HSIL, there was no
group that could be returned to even less frequent
co-testing
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Kaiser >30 year old women
5 year risks of recurrence after treatment varied by
antecedent screening result and path
Pap –Cytology
Colpo biopsyhistology
5 year risk of
recurrence post rx
ASCUS/HPV+ or
LSIL
CIN 2
5%
ASCUS –H or worse CIN3/ACIS
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16%
No subgroup of women achieved risk sufficiently low to
return to the new routine screening
Recommendation is co-test at 12,24,36 months then
“routine”
-after any abnormal cytology ?
-after any abnormal histology?
-after treatment for histologic abnormality?
Recommendations for surveillance post
abnormality -based on weakest data,
may be misleading
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Cost effectiveness study
Surveillance strategies after treatment for HSIL
Hypothetical
Women >30 yo British Columbia Cohort Study
Results: Paps at 6 and 12 months followed by annual
conventional cytology surveillance reduced cervical cancers
and cancer death compared with triennial cytology
HPV cotesting increased cost but did not improve outcome
Adding colposcopy at 6 months for high risk women,
increased life expectancy
Makes key points with respect to how data is interpreted and
understood with respect to guideline development.
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Cost and benefits need to be considered and may vary
with different life situations/populations.
Q 3 year Pap or q 5 year cotesting are known to increase
cancer rates relative to annual cytology.
Adverse effects of treatment (LOOP) may have been
overstated.
Annual cytology remains the gold standard for cancer
prevention
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Studied cost-effectiveness of current screening practice
v. guideline screening
Used data from New Mexico HPV Pap registry
Assumed pap q 3 years 21-65 OR pap q 3 years 21-30
and Cotesting q 5 years
Assumed 100% compliance with colposcopy for
abnormals and 100% compliance with excisional
procedures as per guideline
Found that the most cost-effective option was pap q 3
years with evaluation of all abnormals and excisional
treatment of all precancers as per guideline
Over and under screening/management were both less
cost-effective
Did not stratify by risk group or prior treatment
From: Inefficiencies and High-Value Improvements in U.S. Cervical Cancer Screening Practice: A CostEffectiveness AnalysisImproving U.S. Cervical Cancer Screening Practice
Ann Intern Med. Published online September 29, 2015. doi:10.7326/M15-0420
Date of download: 10/15/2015
Copyright © American College of Physicians. All rights
reserved.
Screen q 3 years or cotest q 5 after 30 if all
normal results
 Evaluate all abnormal results
 Treat all HSIL, AIS or persistent LSIL (in some
cases)
 Ensure 100% compliance with screening,
evaluation and management
Treat all patients with a history of abnormal results or
an inadequate screening history as “high risk” and
increase surveillance of this group
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HPV 16/18 account for 77% cervical cancers
and 54% high grade lesions in US
As successive cohorts are vaccinated, fewer
women may get these infections
Primary screening with HPV and triage to
cytology might be the logical next step
Canadian Cervical Cancer Screening Trial
Women ages 30-69
Compared conventional Pap and HC2
Mayrand, M-H. N Engl J Med 2007 Human
Papillomavirus DNA versus Papanicolou Screening
Tests for Cervical Cancer
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Combined results of 4 studies (Sweden, the
Netherlands, England and Italy).
Primary HPV 60-70% greater protection against
invasive cervical cancer than primary cytology
after first 2.5 years.
Negative HPV at 5 years had better negative
predictive value (NPV) than normal cytology at 3
years.
However, studies involved many different
treatment and management algorithms reporting
markedly different costs for screening, depending
on strategies used.
Methods:
Cobas HPV test
 Cytology and HPV co-collected
 Options compared included:
 Reflex HPV
 Hybrid (cytology under 30 and cotesting above 30)
 Primary HPV with 16/18 triage or cytology triage (if
HPV12+)
Results:
Primary HPV detects more CIN2+ but at cost of more
colposcopies
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Limitations of the study:
Only 3 years of follow up data
Patients managed by specific study
algorithms which may not be available in
all clinic settings.
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12,000 women are still getting cervical
cancer in the US—could we initiate primary
HPV screening on unscreened women?
Young women who have been vaccinated
have a lower risk of getting HR HPV, so
fewer women will test positive and need
evaluation. HRHPV screening may increase
detection of AIS in this age group.
Primary HPV
Screening
Options for
triage for
HPV+
16/18
Cytology
VIA
Colpo
• Different situations determine which is best
• Need ongoing studies to guide management
See & Treat
Ultimately a combination of vaccine in younger
women and screening for carcinogenic HPV in
older women may revolutionize cervical cancer
prevention
See Schiffman, M, Castle, PE. The Promise of Cervical Cancer Prevention.
NEJM 353:20, 2101-2104, 2005