Download Overview of HPV/CC screening guidelines - 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.
The first screening test used to prevent cancer is the Pap
test. Screening is detecting disease in asymptomatic
patients.
 1923-Dr



Papanicolaou
discovers Pap
1960s-ACS endorses
screening
1980s first ACS
guidelines for Pap
screening
“The most successful
cancer screening test”
Successful Cervical Cancer Prevention
Requires a programmatic approach
including:
 primary vaccination
 screening
 active management of abnormalities to
prevent progression
How are we doing?
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…

Global Incidence and Mortality Rate
of Cervical Cancer
US Guidelines

2012, 2016 Screening
 Intended for low risk women only
 Evidence based, easy to understand
 Definition of High Risk varies by organization, but
includes immunosuppressed patients and those with
a history of abnormal or inadequate screening

2013 Management
 Not clearly evidence based, much “expert opinion”
 Many different algorithms for different subgroups
 Complex, hard to understand
Who is excluded from these
guidelines?
ASCCP excludes “high risk” patients
 ACOG: HIV positive,
immunosuppressed, DES
 NCCN: HIV, solid organ transplant, or
long term steroid use, DES
 USPTF: excludes “high risk” patients
 AMA: not addressed
 WHO: HIV, prior treatment for dysplasia
 ACP: Excluded

Screening and Management Guidelines
(simplified )
Screen each woman every 3 years with
pap until 30 and every 3 years with
co-testing thereafter and refer every
abnormality to GYN for discussion of
need for colposcopy.
Of note, patients with a prior history of
any abnormal result and or
symptoms may need more frequent
testing
Normal Screening for asymptomatic low risk
women with all normal results
<21 No pap testing (unless symptomatic or
abnormal exam)
Recommended: annual urine GC/CT testing OR
cervical GC/CT with pelvic exam if symptomatic
21-29 Pap (with reflex to HPV) every 3 years
Annual STD screening recommended through age
25; to continue annually after 25 for women with any
new sex partners, partner who is not monogamous,
drug use, pregnancy, other risk factors
30-65 Pap and HPV co-testing every 3 years
Can you screen at 5 years?
If you confirm that the patient has a
lifetime h/o of normal paps and
negative HPV tests, q5 years cotesting is acceptable
Note that these are the only women to whom the 5
year screening interval applies in the ASCCP
guidelines.
Kinney, Walter, et al, Increased Cervical Cancer Risk Associated With Screening at Longer
Intervals, Ob& Gyn. 125(2):311-315, February 2015
When can you stop screening?
May exit screening ONLY if following criteria are met
If not, continue screening until they are.
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H/o adequate negative screening—defined as 3 consecutive
negative cytology results or 2 consecutive negative co-tests
within the last 10 years and most recent test occurring within
the past 5 years
No immunosuppression
No history of dysplasia in past 20 years

New data suggests benefits to continued screening after
age 65
Rosenblatt, KA. Et al Case-Control study of cervical
cancer and gynecologic screening: A SEER-Medicare
analysis. Gynecologic Oncology 142 (2016) 395-400

Remember, 1/3 of cervical cancers occur in women over 65, most of
whom are unscreened or underscreened.
:
Special Populations: HIV+

Pap test when
 first diagnosed or
 when they first seek prenatal care or
 Within a year of onset of sexual activity- by age 21
After 3 consecutive normal annual Paps, screen….
Every 3 years with Pap only if <30
Every 3 years with co-test in 30+
Any abnormal cytology result or HPV  follow regular
guidelines for evaluation
 Evaluate all abnormal results in younger women
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Other Special Populations

Immunosuppressed (i.e., organ
transplant, autoimmune disease on
immunosuppressant medications):
recommend HIV+ guidelines

DES Exposed: Annual paps without
reflex to HPV (as long as they remain in
good health—i.e. with life expectancy >
10 years)
Hysterectomy
Discontinue screening after total
hysterectomy (i.e., cervix was removed)
for benign disease (anything other than
cancer or CIN2-3) if no history of
dysplasia.
 If hysterectomy done for CIN 2-3, or if
history of dysplasia, continue vaginal
paps as recommended for LEEP followup (see below).

Screening Abnormalities in Low Risk Women
(non-pregnant women ages 25+)

COLPO NOW:
ASCUS HPV+, LSIL, AGC, ASC-H, HSIL, HPV
16/18/45
REPEAT PAP/COTEST IN ONE YEAR:
first time ASCUS HPV negative
` NILM HPV positive, but 16/18/45 negative

If either test is again abnormal in one year then
perform colposcopy for any abnormality of Pap
OR HPV
Long Term Risk of CIN3+ after HPV infection:
role of persistence
Kjaer, et al. J Natl Cancer Inst 2010 Oct 6; 102(19):1451-3
8656 women in Denmark
Co-testing-underwent pap and HC2 testing
2 exams, two years apart
Then followed in registry for 12 years
Estimated risk of CIN3+for women
who were HPV16+ at two years
apart=47.4%
Risk of CIN3+ after HPV negative= 3%
Evaluation of patients with AGC
Age < 35 Colposcopy with ECC
regardless of HPV status
 Age 35+ or other risk factors for
endometrial CA (e.g. morbid obesity,
diabetes) Endometrial biopsy in addition
to colposcopy with ECC

Management after colposcopy
If Pap before colpo: ASCUS/LSIL/NILM
Colpo result: CIN1 or less
PLAN:
1) Repeat Pap and HPV co-test in 1 year  if anything is
abnormal re-colpo.
2) Repeat this cycle annually until co-test is negative, then
co-test q3 years for at least 10 years (even if >65)
3) Patients with persistent ASCUS, LSIL or NILM HPV
positive Paps but negative colposcopy for >= 2 years
may opt for diagnostic LOOP rather than ongoing frequent
colposcopy
If Pap before colpo: HSIL, ASC-H, AGC
Colpo result: CIN 1 or less
PLAN:
1) Repeat Pap and colposcopy in 6 months and cotest at
12 months
2) If all results negative, co-test at 24 months if any
result (either Pap or HPV test) is abnormal re-colpo.
3) If all results negative, co-test q3 years OR annual Pap
testing for at least 20 years (even if >65)
Colpo result: CIN2/3
PLAN
LEEP
May consider observation with q6 month colpo for 1 year if
CIN2 and is younger than 25
Abnormal Pap Results during Pregnancy

ASCUS HPV+ or LSIL
Defer repeat Pap/colposcopy to 6 weeks
post-partum

HSIL, ASC-H and AGC
Colposcopy once in the first or second
trimester during pregnancy, and biopsy
of you are concerned about cancer
Special Populations:
25 and younger
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

ASCUS/ HPV+ or LSIL or LSIL HPV+ ->
Colposcopy initially; if LSIL or better -> Repeat
Pap in 1 year; if repeat Pap ASCUS/
HPV+/LSIL or less, repeat in another year. If
still ASCUS HPV+/LSIL at 2 years (or if
becomes 25), refer for colposcopy
HSIL, ASC-H-> Colposcopy now
CIN 2 on biopsy-> If patient desires future
childbearing, and colposcopy is satisfactory,
then may observe with q6 month
Pap/colposcopy for up to 2 years or LEEP
Other results
No Endocervical component (i.e. no transformation zone cells) are now
treated like normal NILM Pap tests. No earlier repeat testing is needed
Unsatisfactory (i.e. insufficient cellularity)
HPV- or HPV not done

Repeat pap and HPV in 2-4 months, may premedicate with estrogen pvfor 6
weeks
If unable to obtain adequate specimen  colposcopy
HPV+

Colposcopy
Lower cellularity specimens may be acceptable in women who have undergone
hysterectomy for malignancies, chemotherapy, or radiation therapy.
Endometrial cells (benign) on a pap test
Post-menopausal patient Endometrial biopsy
Pre-menopausal patient No action necessary (*though note if patient has
irregular menses may require endometrial biopsy for that indication)
Women with autoimmune
diseases
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
Variable Risk of Cervical Precancer and Cancer After
a Human Papillomavirus-Positive Test
Castle, P. Obstet Gynecol 2011:117:650-6
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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
Surveillance after treatment for CIN2/3
ASCCP guideline
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Co-test at 6 months, 1 year, 2 years, and 3
years from the time of LEEP, then cotest every
3 years OR annual Pap for at least 20 years.
Colposcopy for any abnormality
Screening should continue even if the patient
is over age 65
If anything is abnormal re-colpo
(Including for results that would normally be a
1 year return i.e. ASCUS HPV neg, NILM
HPV+) as their baseline risk is too high to
watch these results
Surveillance after treatment for CIN 2/3
Melnikow, J et al Obstetrics & Gynecology 116, 5, November 2010
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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 co-testing increased cost but did not improve
outcome
•
Adding colposcopy at 6 months for high risk women,
increased life expectancy
Increased Cervical Cancer Risk Associated
with Screening at Longer Intervals
Kinney W, Wright T, Dinkelspiel H, Defrancesco M, Cox T, Huh W Obstetrics and Gynecology.
Vol 125, No.2, February 2015
Makes key points with respect to how data is interpreted and
understood with respect to guideline development.
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

Why don’t these guidelines work
better at preventing cancer?

Guidelines are complicated


(see Davis, M et al. Making Sense of Cervical Cancer Guidelines)
New Guidelines may miss cancer, especially in
women under 30
 (see Nitschmann, C et al. Screening History Among Women with
Invasive Cervical Cancer in an Academic Medical Center)

We don’t always have good systems for tracking and
follow-up of abnormal results
 (See Schapira, M et al . Inadequate Systems to Support Breast and
Cervical Cancer Screening in Primary Care Practice)

Patients may still have barriers to care
 (see Luckett, R, et al Effect of patient navigator program on no-show
rates at an academic referral colposcopy clinic.)
Cervical Cancer Prevention: Australia

Comprehensive screening program with one Pap every 2 years
beginning at age 18 until age 69. Started 1991. Since then
cervical cancer rates have halved.

All patients in registries which collect cytology and histology
data on all patients

First country to role out comprehensive school based vaccine
(Gardasil) program for both girls and boys 2007 (70%
vaccinated)

Within 2 years of roll out of vaccine program there was a 38%
decrease in the rate of high grade dysplasia among eligible girls
Brotherton, J. et al. The lancet .com vol 377 June 18, 2011
Cervical Cancer-2016

The etiology of cervical cancer is known (HPV)

Effective prevention involves
 Primary prevention (vaccine)
 Secondary prevention (screening test +
management programs)

Nanovalent vaccine (Merck) has the potential
to prevent 80-90% of cervical cancer and most
condylomata

Technology and practice are changing rapidly
Will we be able to eradicate cervical cancer in our lifetimes?
Given how far we’ve come, anything may be possible…