Ann Laros, MD
University of Iowa
Sept 17, 2013
Less is more
 (Pap smears)
More is more
 (Vaccinate all)
Source: NCI, 2005
Source: NCI, 2005
3



Cervical cancer was #1 cancer killer of
US women until 40 years ago
Pap widely implemented through 1970s
Currently in US
 12,000 diagnosed annually
 4,000 die annually
▪ Similar to US motorcycle fatalities
 Most cancers are found in women who
▪ NEVER had a Pap (50%)
▪ OR had a Pap more than 5 years prior (10%)



More than 100+ HPV virus types
40+ types infect the genitals of men and
women
14 HR HPV types (oncogenic)
 HPV 16/18 most common
 HPV vaccines protect against these
▪ HPV2
HPV 16/18
▪ HPV4
HPV 6/11 and 16/18
 Nano-valent vaccine in Phase 3 trials

Genital HPV is spread by genital to genital
contact.
 HPV can be spread by same sex encounters.

Condoms decrease the spread by about 75%,
but do not prevent it.

No real test for HPV

Most infections resolve in 1-2 years

60-70% sexually active college students have HPV
 20% risk with each partner
 70-80% life time risk

HPV causes genital warts
 1% young men/women get genital warts each year
 10% life time risk

HPV causes abnormal Paps
 10% of young women will have an abnormal pap each year
 40% life time risk






Why?
Why so much change?
Did we really need to change?
Are they safe?
Are we going to miss cancers?
How do we do this and the Affordable Care
Act too?
Dr. Melik: You mean there was no
deep fat? No steak or cream pies or
hot fudge?
Dr. Aragon: Those were thought to
be unhealthy—precisely the
opposite of what we now know to
be true.
—From the 1973 Woody Allen
comedy “Sleeper.”

Develop evidence based cervical cancer
prevention guidelines to best serve women,
independent of cost


4,000 articles, 1.4 million women over 8 years
Stakeholders
 ACHA, ACOG, AAFP, ACS
 Nurse Practitioners in Women’s Health
 Planned Parenthood, + 21 more

Recommendations were presented,
discussed prior to vote

66% agreement before acceptance
First do
no harm

NO Paps before age 21

Paps every 3 years age 21-29

Paps every 3-5 years 30-65
 Normal Pap, every 3 years
 Normal Pap and negative HPV, every 5 years

No change based on HPV vaccine status

No Paps after 65 or hysterectomy, if no CIN2+
Seriously
▪ Cervical cancer less than 21 is 1/1,000,000

Cervical cancer rates are low in young women
 <21 year olds
 21-25 year olds

1.4/1,000,000
1.4/100,000
When the risk of cancer is low, the risks of a
testing maybe higher.


Age of first pap
<20
 EU country
 Austria, Slovakia(18)

20
 Germany, Greece(4.6),



21
23
25

30
Slovenia(16)
 US(8.5)
 Denmark(12.9), Sweden(8.7)
 Belgium, Czech Republic,
France, Ireland, Italy(8.2),
Poland, Romania(29), UK
 Finland (4.4),

31
http://eu-cancer.iarc.fr
Lithuania(25.6), Netherlands,
Spain
 Bulgaria(25.8)

This is NOT new


The USPSTF recommends screening for
cervical cancer in women ages 21 to 65
years with cytology (Pap smear) every 3
years .
Grade: A Recommendation

We are not alone





Pap interval
Every year

EU Country

Austria, Czech Rep, Germany,
Greece (4.6), Slovakia (18)
Every 2 years
Every 3 years

Bulgaria (25.8)

Belgium, France, Italy (8.2),
Lithuania (25.6), Poland, Sweden

Every 3-5 years

US (8.5), Denmark (12.9), Ireland
(12.9), Spain (7.6), Sweden, UK

Finland (4.4), Netherlands,

Every 5 years
http://eu-cancer.iarc.fr
Romania (29)

The key is getting it done
▪ 50% of cervical cancers in the US occur in women who
have never had a Pap
▪ Finland starts at 30, Paps every 5 years—4.4
▪ Slovakia starts at 18, Paps annually—18
▪ US starts at 21, every year—8.5
▪ Has your mother had a Pap smear?

Two acceptable options for screening in this
population

PREFERRED
 Pap and HPV Co-testing every 5

ACCEPTABLE
 Pap every 3



No HPV testing
Reflex testing
Co-testing

No HPV testing
 Under 25

Reflex testing
 If Pap is ASCUS, then test for HPV
▪ If ASCUS, +HPV—colposcopy
▪ If ASCUS, -HPV—same as normal, follow-up in 3 years

Co-testing
 If Pap is NORMAL, then test for HPV
▪ Some systems get HPV on all co-tested Paps, not usually
useful for LSIL and above

Pap after 30

Normal Pap
 Repeat in 3 years OR HPV testing
▪ HPV negative
▪
▪
▪
▪ Repeat in 5 years
HPV positive
Repeat in 1 year OR
HPV 16/18 testing
HPV 16/18 negative
Repeat in 1 year
HPV 16/18 positive
Colposcopy

No sooner than age 30.

Pap based





Pap
Normal
Normal
OR
HPV
Negative
Positive
Neg 16/18
Pos 16/18
Action
Rescreen in 5 years
Repeat in 1 year w/ co-testing
Repeat in 1 year w/ co-testing
Colposcopy




Normal
LSIL or greater
ASCUS
ASCUS
No Co-testing
No HPV is done
Negative
Positive
Repeat in 3 years
ASCCP guidelines, no change
Rescreen in 5 years
ASCCP guidelines, no change

NEGATIVE PAP
LIQ CYTO
 HPV HIGH RISK RESULT POSITIVE (A)

 HPV 16 GENOTYPE
POSITIVE (A)
 HPV 18 GENOTYPE
NEGATIVE

No screening following adequate negative
prior screening
 Even if they have a new partner!!

“Adequate negative prior screening” not
defined
 IF history of CIN2+, routine Pap for 20 years
▪ Every 3 years

Paps screen for cervical cancer, NOT vaginal
cancer.
 Vaginal cancer is NOT common (840 deaths/year)

Exceptions:
 Cervix remains (supracervical hysterectomy)
▪ Follow guidelines until age 65
 CIN2+ including cervical cancer

No changes in frequency.
 As of 2010, 20.5% women age 19-26 reported > 1 HPV
vaccine
 This low vaccine uptake is a barrier to making
population based changes.
 Iowa was among the worst
 Look for vaccine related changes no sooner than
10 years.


Iowa Lags Behind Rest of US in HPV Vaccination
Iowa’s vaccination rate for genital human papillomavirus (HPV) is below
the national average, which itself has a low rate of compliance, according
to Philip Colletier, president for the Polk County Medical Society. A recent
CDC report showed that only 33 percent of children had completed the
three-shot sequence since the United States approved it in 2006 for girls
and in 2009 for boys. Colletier said that Iowa’s completion rate was only
21 percent and education was the key to increasing this rate.
 Des Moines Register (08.23.2013)

Get the HPV vaccine, soon

Men can get the HPV vaccine
 All men up to age 21
 Some men through to age 26

Vaccinate your sons and daughters
 Protect your daughters
 Protect your sons

Vaccinate MSM

Based on “similar treatment for similar risk”
 In addition to large population research studies, data from Kaiser in
California with 1.4 million women over 8 years.

Women of different ages have different risks.
 <21
 21-24
 25-29
 30+

Risk for CIN3+ in 5 yrs
Recommendation

5%
2-5%
.01-2%
.01%
Colposcopy
F/up 6-12 months
Pap in 3 years
Pap/HPV in 5 years




No paps under 21
 If LSIL or ASCUS, ignore those done
 If +HPV, ignore it

No endocervicals cells, no worries

Age matters
 21-24 No HPV reflex testing
 21-24 No colp for LSIL

No more 6 month follow-up

More HPV testing (over 30 and in follow-up of abnormals)

1. Unsatisfactory Pap—Repeat in 2-4 months

2. No endocervical cells—Normal, repeat in 3 yrs

3. ASCUS Pap—Repeat in one year (not 6 mns)

4. ASCUS, -HPV Pap—Normal, repeat in 3 years

5. AGUS—Colp. No HPV triage recommended

Represents inadequate cell collection

HPV testing requires adequate cell collection
as well.
 Many HPV tests don’t have a fail safe for
inadequate vs not present.
 Therefore can’t rely on NEGATIVE HPV in this
setting.

If unsatisfactory x2, immediate colposcopy




With liquid based paps, occurs in 10-20%;
higher in older women.
Review of KPNC, these women a have no
higher risk for CIN 3+
Including patients after treatment for CIN 2+
Remember: In 1950, 4 out of 5 doctors
recommended Camels

Repeat in one year
 If ASCUS or worse—colposcopy
▪ 2 ASCUS leads to colposcopy, but they may be 1 year
apart, instead of 6 months
 If normal—repeat in 3

Women under 25 (21-24) with ASCUS
 PREFERRED: No reflex HPV testing; repeat in one
year x2.
 ACCEPTABLE: Reflex HPV testing, OK*
 *Neither ASCUS HPV+ nor HPV- women go to
colposcopy.

“Normal”
 Repeat in 3 years (not 5)
 If 65, this should not be the last Pap
▪ Repeat in one year

1. No colp for women under 25 with < LSIL

2. Moderate dysplasia can be followed in
“young women”.
 Followed with colp in 6 months for up to 2 years
 50% resolve

LSIL and HPV testing
 Recommend reserve only for postmenopausal

Stigma of HPV
Anxiety of disease, follow-up
Cost and time for follow-up
Pain and injury from follow-up

Increased risks for preterm delivery




Recommendations for women sexually active
under 21







Folic acid daily
Chlamydia testing yearly
Flu vaccine annually
(HPV vaccine complete)
(Effective contraception)
(Exercise and healthy diet)
No Pap

1 in 8 babies delivers prematurely in the US
 Too much Pap testing led to too many biopsies and
too many treatments and is one of the factors
contributing to preterm birth




Cervical cancer is not hereditary.
Most HPV infections resolve in 1-2 years
We are not looking for mildly abnormal cells, but
severely abnormal cells
On average it is 3-7 years from CIN3+ to cancer



Cervical cancer is a disease of younger
women, peak age 40.
Breast, colon cancers increase
Heart disease increases more
 Regular exercise and a healthy diet

Is it safe to
 Do a physical without a routine UA?
 Give the pill without a cholesterol?
 Give the pill without a Pap?
 Place an IUD in a nullipara?
 Eat margarine?
 Do Paps every 3 years?


How well are we doing?
Quality assurance audits
 Paps under 21
 Colps/referrals under 25 (ASCH, HSIL, AGUS only)
 HPV vaccinations men <21
 Back to back Paps after 2013
Test
time

19 y/o presents for yearly and birth control
 Sexually active since 15
 19 sexual partners, HSV
 Mother with cervical cancer
 Last Pap 3 years ago





A. It has been 3 years, do Pap
B. No Pap, test for HPV
C. No Pap, test for Chlamydia
D. She is at high risk, do Pap
E. Chastity belt and Mom talk

Answer, C.
 No Paps before age 21, SERIOUSLY
 Chlamydia testing is recommended for all sexually
active women under 26 yearly
 Sexually active women are likely to have HPV,
don’t test women under 30 for HPV
 Cervical cancer is not heritable. It is caused by the
HPV virus

33 year old G2P2 for annual exam
 No abnormal Paps
 Pap today is normal

When is her next Pap due?
 A. Next year
 B. 3 years
 C. 5 years

Answer, B
 Paps every 3 years
 If co-testing with HPV had been ordered and
 HPV was negative, then 5 years
 Take home lesson,
 Unless your provider is George Clooney or
McDreamy , ask for HPV co-testing with your
Pap

20 year old
Pap: ASCUS, +HPV

Options

 A. Refer for colposcopy
 B. Repeat Pap in 6 mnths
 C. Repeat Pap in 12 mnths
 D. Repeat HPV in 12 mnths

Answer, C.
 Repeat the Pap in 12 months.
Send the referring provider, up to date and
informative follow-up letter.
 Set up a QI/QA survey in your own department.



STRONG recommendation for no Pap until age
21.
IF Pap obtained before 21, ignore unless CIN2+

50 year old P5
 Last Pap 201o. No abnormal Paps
 Hysterectomy for fibroids

When is her next Pap due?
 A. Today, it has been 3 years
 B. Every 5 years if HPV was negative
 C. Never more. Thank Gosh for evidence based
medicine

Answer, C. Never more
 Primary care providers ARE great
Modeled impact of target screening age on incidence of cervical cancer*
Target Age (years)
20–64
25–64
30–64
35–64
Reduction in CA Incidence (%) No. of Tests
84
9
84
8
81
7
77
6
Modeled using a 5-yr screening interval ,assuming a 70% sensitivity of the 1st screening test.
Data from IARC: Working Group on Evaluation of Cervical Cancer Screening Programs:
Screening for squamous cervical cancer. BMJ 293:659, 1986.

40 year old P2
 Supracervical hysterectomy
 Pap with HPV co-testing
▪ Pap= NORMAL
▪ HPV=POSITIVE

What do we do now?
 A. Repeat Pap in one year
 B. Repeat Pap in 3 years, it is normal
 C. Refer for colposcopy
 D. Refund her money, she didn’t need a Pap, she
had a hysterectomy

Answer, A. Repeat in one year.

Normal Pap
 Repeat in 3 years OR HPV testing
▪ HPV negative
▪
HPV positive
Repeat in 1 year OR
 We are looking for precancerous cells, not HPV
 If HPV 16/18 positive, then COLPOSCOPY
 Supracervical hysterectomy, leaves the cervix

25 year old
Pap: ASCUS, HPV negative

Options:

 A. Refer for colposcopy
 B. Repeat Pap in 6 months
 C. Repeat Pap in one year
 D. Repeat Pap in 3 years

Answer: D, Repeat Pap in 3 years

Question:
 Does the risk of precancerous change in women with
ASCUS, HPV- warrant greater surveillance than normal
Pap, HPV-?No


Negative HPV is great.
Studies show no different in risk compared to
negative co-test (neg Pap and neg HPV).


21 year old
First Pap: LSIL

Based on 3/2013 guidelines





A.
B.
C.
D.
E.
Colposcopy
HPV testing, colposcopy of HPV+
HPV 16/18 testing, colposcopy if either positive
Repeat Pap in 6 months
Repeat Pap in one year

Answer: D, Repeat Pap in 1 year

In a young healthy woman, likelihood of
resolution in 1-3 years is high, 90%
Likelihood of developing cancer in this time,
low, low.


21 year old
First Pap: HSIL

PLAN:

 A. Colposcopy
 B. HPV testing, colposcopy if positive
 C. HPV 16/18 testing, colposcopy if positive
 D. Repeat Pap in 1 year

Answer, A. Colposcopy

High grade, is still high grade
Avoid HPV testing under 30





32 year old
LEEP for moderate dysplasia age 22
All normal Paps yearly since
Pap: Normal

Options:




A.
B.
C.
D.
Colposcopy
Repeat Pap in 1 year
Repeat Pap in 3 years
Repeat Pap and co-testing in 5 years

Answer: C, repeat Pap in 3 years
 After treatment for CIN2+, there is an increased risk
for cancer that lasts 20 years.
 Recommendation has been for regular/annual Pap
smears for 20 years. Now, Pap every 3 years for 20
years, even if this puts her greater than 65.
 Initial clearance, co-test (Pap and HPV) at 12 and 24
months. If all negative, every 3 years for 18 more
years.

27 year old
Mild dysplasia on colposcopy

PLAN:

 A. Repeat Pap in 6 months x2
 B. Repeat Pap in 1 year
 C. HPV testing
 D. Cryo

Answer, C (preferred); (or A, acceptable)

HPV testing in one year
 If POSITIVE , repeat colposcopy
 If negative, return to routine screening
 OR

Pap x2 6 months apart.
 Colposcopy for ASCUS or greater

21 year old
Last Pap LSIL, 18 months ago
No follow-up w/ recommended colposcopy

Options


 A. Refer for colposcopy
 B. Pap with HPV testing
 C. Pap only today
 D. HPV testing only today

Answer, C
 Colposcopy is no longer recommended for
women under 25 unless HSIL/AGUS.
▪ After 1 year, 70% of mild dysplasia is resolved
▪ After 3 years, 90% of mild dysplasia is resolved
 Follow LSIL for 24 months in women <25.
 Generally avoid HPV testing in women <30,
▪ except with ASCUS or in follow-up of known MILD
DYSPLASIA until age 30.

53 year old
 Pap normal, no endocervical cells

Plan:
 A. Repeat in 2-4 months
 B. Repeat in 1 year
 C. Repeat in 3 years
 D. Repeat in 5 years

Answer: C, repeat in 3 years
 If she had had HPV “co-testing”, 5 years.
 2-4 months is for UNSATISFACTORY, meaning
not enough cells, not no endocervical cells

34 year old P5 with LSIL Pap
 Colp adequate, Cx bx: Mild dysplasia
 EndoPap: LSIL

Options
 A. LEEP or Cone biopsy
 B. Cryo or laser
 C. HPV testing at one year
 D. Pap x 2, 6 months apart

Answer: C (preferred); D (acceptable)
 LSIL or CIN 1 in endocervix is NOT indication for
LEEP/Cone and should be treated like mild
dysplasia.
 Treatment is NOT recommended for Mild
dysplasia

23 year old with history of an abnormal Pap
 She thinks she had colposcopy.
 She recognizes mild or moderate dysplasia, NOT
severe.
 She does not remember cryo (freezing and
thawing), laser (burning with smoke
evacuator/vacuum), LEEP
 She recalls a normal Pap last year, 2011.

Options (Records are not available)
 A. Pap only today
 B. Pap with HPV testing today
 C. HPV only testing
 D. Repeat pap in 3 years

Answer: No true answer
 Based on her history recall and age, most likely
abnormal Pap is LSIL or ASCUS, +HPV.
 IF colp was performed and no treatment was
recommended, either unremarkable or mild
dysplasia.
 IF mild dysplasia, 2 Paps or one HPV test is
adequate follow-up.

MY answer
 Ask your gynecologist or referring entity
 A. Pap only today

24 year old
Humira for Rheumatoid Arthritis
Pap last year normal

Does she need a Pap this year?


 A. Yes
 B. No

Answer: No data. No recommendations

Probably yes, her medication weaken her
immune system and her ability to clear the
virus.