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The Pelvic Exam
including
Cervical Cancer Screening
VETERANS HEALTH ADMINISTRATION
Learning Objectives
Discuss the epidemiology and etiology of cervical cancer
Review latest screening guidelines
Describe how results are reported
Explain how to manage abnormal results
Discuss indications and benefits of the HPV vaccine
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Why Screen for
Cervical Cancer?
• 12,000 cases/year
• 11th cause of cancer death
• 85% death reduction due to screening
• 50% of cases are in women who have
never been screened
Photo courtesy of peir.net
• 10% of cases are in women with no screening in 5 years
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Risk Factors for Cervical Cancer
• Chronic HPV infection
• In utero exposure to
diethylstilbestrol (DES)
• At-risk for contracting HPV
−
−
−
−
−
Hx of multiple sexual partners
HIV/immunosuppression
Early age of first intercourse (<17)
Multiple pregnancies
Long-term oral contraceptive use
• Risks for not clearing HPV
− Smoking
− HIV/Immunosuppression
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• Screening issues
− Low socioeconomic status
− Immigration from a
country where screening
is not the norm
HPV
• Group of >150 related viruses
High-Risk
Types
Low-Risk
Types
16 & 18
6 & 11
• Causes 100% of cervical cancers
• Two high-risk types (16 and 18) cause 70% of cervical cancers
• Persistent infection is necessary to develop cancer
• Low-risk subtypes (6 and 11) cause genital warts or mild cervical
dysplastic changes that do not usually progress to cancer
• 70% of new HPV infections spontaneously clear within one year; up
to 91% clear within two years.
• Patient may remain immune to that subtype for up to 3 years
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Incidence of 6/11/16/18 HPV
New infection is less likely with older age
Age group
Incidence/100 person years
24-29
30-34
35-39
40-45
7.4 (5.9 – 9.2)
3.6 (2.4 – 5.1)
2.4 (1.5 – 3.6)
1.9 (1.2 – 3)
Older women are less likely to clear infection
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Screening Guidelines
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Things to keep in mind with cervical
cancer screening guidelines…
•
•
•
•
Natural time course is long
HPV will often clear on its own
Guidelines do not always fit
Do no harm
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Start Screening at Age 21. Why?
1. Invasive cervical cancer is very rare in women under 21 (<0.1%).
2. Although the rate of HPV infection is high among sexually active
adolescents, the immune system in most of these women clears
the HPV infection in 1-2 years.
3. Adolescents have a higher incidence of HPV-related
precancerous dysplasia because the cervix is immature, but
most lesions resolve without treatment.
4. Women treated with excisional procedures for dysplasia have
more premature births. Adolescents have most of their
childbearing years ahead of them; thus it's important to avoid
unnecessary procedures that negatively affect the cervix.
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How Frequently Should We Screen?
Women Ages 21-29
Screen at 3-year
intervals with
cytology
Not necessary to test for HPV; it
is often present and most likely
will resolve
Compared to annual screening…
USPSTF, ACS, ASCCP
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• No significant differences found in
lifetime risk of cancer
• Annual screening resulted in twice
the colposcopy rate
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How Frequently Should We Screen?
Women Ages 30-65
Option 1
Co-testing…
Provide
similar
benefits
Cytology + HPV at 5-year
intervals
Option 2
Cytology at 3-year intervals
if HPV co-testing is not
available
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When to Stop Screening?
Adequate screening =
• 3 consecutive negative Paps
or
• 2 consecutive negative Paps
with negative HPV results in
the 10 yrs prior to screening
cessation with most recent
test in the last 5 yrs
Discontinue at 65
with adequate
recent screens AND
no hx of high grade
dysplasia or worse
Do not resume screening
once stopped
History of high-grade lesion
or cancer, screen routinely
for 20 years after diagnosis
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Special Considerations
• High-Risk Conditions
– History of high grade cervical lesion, DES exposure in utero,
transplant, or immunocompromised patient
• Screen more frequently
• After Hysterectomy
– No screening if cervix was removed and no previous high
grade lesions or cancer
– If a cervix is present, screen!
• Woman may not know if her cervix was removed.
Provider may have to look.
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If the exam of the cervix was abnormal, do not
be reassured by a normal Pap report… REFER!
Dear Dr. GYN:
Help!
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Pap Smear
Collection Supplies
• Endocervical brush and
spatula used together
─ Brush samples endocervix)
─ Spatula samples ectocervix
• Broom-like device may be
used alone
─ Longer bristles are inserted in
cervical opening to sample
endocervical canal
─ Shorter bristles sample
ectocervix
Photograph courtesy of Michael Crawford
/ Bpac NZ
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Pap Collection Processes
Slide
Preparation
Method
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Liquid
Cytology
Method
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Slide Preparation Method
Assisting During a Pelvic Exam
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Liquid
Cytology
Method
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ThinPrep® (one liquid-based
cytology brand)
Conventional Pap smear slide
Images provided courtesy of HOLOGIC, Inc. and affiliates
Liquid-based cytology provides:
1. Ability to do reflex HPV testing
2. No differences in detection of high grade lesions
3. Better detection of glandular abnormalities
4. Ability to perform Pap smears during menstruation
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Specimen Adequacy
(satisfactory, unsatisfactory)
Bethesda
Reporting
System
Descriptive Diagnosis
(conventional slide vs. ThinPrep)
General Categories
Negative for intraepithelial
lesion or malignancy (“normal”)
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Epithelial cell abnormality (will
also indicate if it is glandular
or squamous)
Specimen Reports
Unsatisfactory for
interpretation (not
enough cells)
Repeat Pap in 2-4
months
Satisfactory but no
endocervical
cells/transformation
zone (EC/TZ) identified
or partially obscured
Follow usual
screening guideline
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Microscopic Appearance (Photos by Dianne Solomon, MD)
Normal
ASC-US
High-Grade
Low-Grade
Cancer
Abnormal Pap Smear Terminology
Cytology
(Pap) Terms
Histology
(BIOPSY) Terms
Lay Terms
ASC-US
Atypical squamous
cells of uncertain
significance
Atypia or metaplasia
Inconclusive.
Needs follow-up.
ASC–H
Atypical squamous
cells, cannot rule
out high grade
Varies
Refer for
colposcopy; 1%
malignant
LSIL or
LGSIL
Low-grade
squamous
intraepithelial lesion
Cervical intraepithelial
neoplasia 1 (CIN1) = mild
dysplasia
Refer for
colposcopy; 1%
malignant
HSIL or
HGSIL
High-grade
squamous
intraepithelial lesion
CIN 2 = moderate dysplasia
CIN 3 = severe dysplasia
AGC
Atypical glandular
cells
Refer for
colposcopy; 1-5%
malignant
Glandular atypia mild/severe Colposcopy and
endometrial bx;
Adenocarcinoma in situ (AIS) 30% malignant
Pap reports may also mention…
Organisms Trichomonas (treat)
Candida
Garnerella (bacterial vaginosis). Not normally treated if seen
on Pap smear, especially if exam was normal.
Actinomyces (typically found in women with an IUD; does
not need treatment)
Changes seen with herpes (will be described as
“multinucleated giant cells”)
Reactive
Changes
Inflammation related to infection or irritation (organism is
not usually identified). Repeat Pap in 6 mos if patient is HIV
positive or immunocompromised.
IUD-related
Atrophy
Benign endometrial cells (investigate for endometrial cancer
in women over 40)
Epithelial Cell Abnormalities
(7% of women receiving Paps each year)
• Squamous Cell Abnormalities
−
−
−
−
ASC-US, including ASC-H (2-3 million; 3% of smears)
LGSIL (1.25 million)
HGSIL (300,000)
Squamous cell carcinoma (12,800; 90% of cervical cancers)
• Glandular Cell Abnormalities
− Atypical glandular cells (AGC)
− Endocervical adenocarcinoma in situ
− Adenocarcinoma (10% of cervical cancers)
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Biopsy Findings by Pap/HPV Result
Pap result
Normal Pap
ASC-US, HPV neg
CIN1
CIN2/3
Cancer
up to 10%
<1%
0.25%
<10%
<1.5%
<0.01%
<1.1%
<0.08%
Normal Pap, HPV+
ASC-US, HPV+
50-60%
7-18%
<0.1%
LGSIL
50-60%
2-19%
0.16%
HGSIL
20%
up to 70%
7%
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HPV Testing Alone
• HPV has increased sensitivity to detect CIN2/3
• Increased negative predictive value
• Concerns about inadequate sampling, lack of a
standard, and providing false assurance due to false
negative results
• Problem with the positive predictive value -- no
defined management strategies
• Potential harms from increased colposcopies
• More data is needed and not recommended
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When is HPV Testing Useful?
HPV testing has higher sensitivity and lower specificity
than Pap with less variability
1. Triage inconclusive ASC-US Pap results
─ If liquid-based cytology is used, residual cells from the vial can be
tested for high-risk HPV (reflex testing)
─ If your facility still uses slides for Pap collection, ASC-US results can be
triaged with a repeat Pap, colposcopy referral, or ordering an HPV test
2. After colposcopy, if no CIN2,3 is found—will show if persistent
HPV is present
3. Can stratify postmenopausal women or women age <25 with LSIL
4. Co-testing for women ages 30-65
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When is HPV Testing Not Useful?
• Females <30 unless ASC-US Pap result (HPV is more
likely to be present in this age group)
• Prescreening for HPV vaccination
• STI screening
• Women >25 years of age with ASC-H, LSIL, HSIL results
(refer for colposcopy regardless of HPV status)
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When HPV is +, but cytology is normal…
Women ages 30-65
At one year, risk is high enough to warrant repeat
co-testing in one year but not high enough for an
immediate colposcopy
CIN3 risk
Cancer risk
1 year
3 years
<1% - 4.1%
2.2% - 7.0%
0.08%
5 years
>10 years
5.9% - 9.3%
16% - 21.2%
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When HPV is +, but cytology is normal…
Women ages 30-65 (cont’d)
• Repeat co-testing in 1 year
− If HPV+, refer for colposcopy (persistent infection)
− If HPV- with cytology of LSIL or more, refer to colposcopy
(high risk of CIN2+)
− If HPV- and cytology is ASC-US or less, screen with co-testing
in 3 years (not 5 years)
or
• Test for HPV 16/18 with genotype testing
− If HPV 16/18 positive, refer to colposcopy (most cancers
occur with these types)
− If HPV 16/18 negative, repeat co-testing in 1 year
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Managing Abnormal Cytology
Results
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ASC-US
Three ways to evaluate…
1. Triage by HPV testing (helps determine risk of CIN2+)
• Standard in >95% of labs if liquid-based cytology is used to
collect Pap smear
• If high-risk HPV+, refer for colposcopy as CIN2+ risk is >15%
2. Repeat Pap
• Repeat Pap in 12 months
• If Pap is ASC-US or worse, refer for colposcopy
3. Colposcopy (in selected circumstances)
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ASC-H
• Risk of CIN 2 or worse is 50%
• HPV triage is not indicated
• Refer for colposcopy
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LGSIL and HGSIL
Risk of CIN2+ is high
• For <25, risk of CIN3+ with LSIL is less than for older women
No role for HPV testing
• Exception: postmenopausal women with LSIL can be triaged
with HPV testing and managed in the same manner as ASC-US
LSIL:
• Women >25, refer for colposcopy
• Women 21-25, repeat Pap in 1 year
− If normal, repeat Pap in 1 year. Negative x 2, return to routine
screening.
− If ASC-US or LSIL, repeat Pap in 1 year. Refer to colposcopy if still
abnormal.
− If ASC-H, HSIL, or AGC, refer to colposcopy
HSIL: All ages, refer for colposcopy
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Glandular Cell Abnormalities
Atypical Glandular Cells (AGC)
•
•
•
•
More likely to be associated with both squamous and
glandular abnormalities
High rates of CIN2+ with this abnormality
Pap smears are less sensitive for detecting glandular dysplasia
and malignancy
Refer for colposcopy and do an endometrial biopsy
AGC-NOS
CIN2/3
9-41%
Cancer
1-9%
AGC
27-96%
5%
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Summary:
Who Needs a Referral for Colposcopy?
•
•
•
•
•
•
HPV(+) on one-year repeat co-testing
HPV subtypes 16/18 genotyped after HPV(+)
ASC-US with HPV(+) (over age 25 or repeated <25)
ASC-US x 2 if no reflex HPV testing done
ASC-H
LGSIL (if post-menopausal, HPV triage may be useful)
− Ages 21-25 repeat 1 year only. If persistent +, refer
• HGSIL
• AGC
American Society for Colposcopy and Cervical Pathology Guidelines
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HPV
Vaccines
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Protects at least 7-10 yr; doesn’t replace regular screening
Well tolerated
Don’t test for HPV before vaccination
$125 per does, $375 for full series
Don’t restart series for missed dose
Gardasil on VA national formulary
Continue to screen as indicated
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HPV Vaccine Facts
More effective if no prior HPV exposure
Two HPV vaccines
Gardasil®
• Quadrivalent vaccine for subtypes
6/11/16/18
• Women and men ages 9-26
• Three 0.5-mL doses IM at 0, 2 mos, 6 mos
• Prevents CIN2 and 3 cancer, genital warts,
anal and vulvar cancers and precursors
Cervarix®
• Bivalent vaccine for subtypes 16/18
• Women ages 9-26
• Three 0.5-mL doses IM at 0, 1 mo, 6 mos
• Indicated to prevent CIN 2 and 3 cancer
• Less protection for genital warts
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Why is the vaccine recommended only
for younger women?
Age
group
Incidence of high-risk subtypes
per 100 person years
24-29
7.4 (5.9 – 9.2)
30-34
3.6 (2.4 – 5.1)
35-39
2.4 (1.5 – 3.6)
40-45
1.9 (1.2 – 3)
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Efficacy of HPV Vaccines
% Decrease in CIN 2 or worse in vaccine group
(vs. placebo)
Women negative for all vaccine HPV types
and per protocol
>99%
Women positive for at least 1 viral type OR
off protocol (missed or late doses)
40 – 60%
Nearly identical for bivalent and quadrivalent vaccines.
Efficacy thus far indicates duration of at least 7-10 years; studies are
ongoing.
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HPV Vaccine Contraindications and Risks
Not for women with
• Pregnancy
• Moderate to severe acute illness
• Yeast allergy
Adverse events
• Fainting in adolescents likely due
to injection process (keep in area
for 15-20 mins)
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The ASCCP has released the updated Consensus Guidelines
on the Management of Women with Abnormal Cervical
Cancer Screening Tests and Cancer Precursors © 2013.
http://www.asccp.org/ConsensusGuidelines/tabid/7436/Default.aspx
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ASCCP APP
Helpful References and Resources
• American Cancer Society. Human Papilloma Virus (HPV), Cancer, HPV Testing,
•
•
•
•
and HPV Vaccines: Frequently Asked Questions.
http://www.cancer.org/docroot/CRI/content/CRI_2_6x_FAQ_HPV_Vaccines.a
sp
American Society for Colposcopy and Cervical Pathology (ASCCP). Algorithms:
Updated Consensus Guidelines for Managing Abnormal Cervical Cancer
Screening Tests and Cancer Precursors. c2013.
http://www.asccp.org/ConsensusGuidelines/tabid/7436/Default.aspx
CDC. HPV Vaccination. 02/07/13. http://www.cdc.gov/vaccines/vpdvac/hpv/default.htm#ed
Massad et al. 2012 updated consensus guidelines for the management of
abnormal cervical cancer screening tests and cancer precursors. Obstet
Gynecol. 2013;121(4):829-46.
USPSTF recommendation on cervical cancer screening, March 2012:
http://www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm
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Authors
Primary:
Catherine Staropoli, MD
VA Maryland Healthcare System
Kathleen McIntyre-Seltman, MD
VA Pittsburgh Healthcare System
Contributors: Linda Baier Manwell, MS
Division of General Internal Medicine, University of
Wisconsin-Madison
Molly Carnes, MD, MS
University of Wisconsin-Madison Center for
Women’s Health Research
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