David Murphy, D.O.
Indiana University Health
Southern Indiana Physicians
Objectives
 Review current recommendations
 Develop an algorithm for the appropriate use of
screening cytology and HPV testing
 Discuss and incorporate into practice the newest
ASCCP/ACOG consensus guidelines for management
of cytologic abnormalities or (+) HPV testing
Essential Changes From Prior
Management Guidelines
 Cytology reported as negative, but lacking
endocervical cells can be managed without early
repeat
 Cytology reported as unsatisfactory requires repeat
even if HPV negative
 Genotyping triages HPV (+) women with 16 or 18 to
earlier colposcopy
 ASCUS- immediate colposcopy is not an option. Serial
cytology at 12 months, and then if negative, cytology
every 3 years
Essential Changes (continued)
 HPV (-) and ASCUS results should be followed with
co-testing q 3 years, rather than 5 years.
 HPV (-) and ASCUS results do not allow exit from
screening at age 65.
 More strategies incorporate co-testing to reduce
follow-up visits.
 Women aged 21 – 24 are managed conservatively
Risk Factors for Cervical Cancer
 HPV infection (16/18)
 Early onset of sexual activity (<16)
 High number of sexual partners (>4)
 Hx of genital warts
 Cigarette smoking
 HIV seropositive
 Immunosuppresive therapy
HPV and Cervical Cancer
 Oncogenic (high risk) HPV types account for >99% of
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cervical cancer
70% of invasive cervical cancer is due to HPV 16 (60%)
and 18 (10%)
Nononcogenic (low risk)
6/11
Cause of genital warts
No role for low risk hpv screening in cancer prevention
HPV and the Development of
Cancer
HPV
 Most young women have an effective immune
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response that clears the infection in an avg of 8
months.
CIN 1 is a manifestation of acute HPV and has a high
rate of regression to normal cells
CIN 2 is a mix of low-grade and high-grade lesions
CIN 3 and AIS are cancer precursors
HSIL is associated with a persistent and transforming
infection and cancer risk.
Colposcopy
 With directed bx remains the standard for disease
detection
 Technique of choice for treatment decisions
 Endocervical sampling
Screening Today
 When to start?
 When to stop?
 How often?
 HR HPV testing
 Continue in patients after hysterectomy?
 No change in women vaccinated against HPV
Principles in Interpreting
Guidelines
 Strategies developed based on risk where similar risk
should have the same management.
 Clinical judgment is necessary in application to
individual patients.
 Current strategies cannot eliminate the risk of
developing cancer.
 Attempts to eliminate often result in unanticipated
harm from excessive evaluation and treatment.
Start screening at age 21
 0.1% of cervical cancer cases
 1-2 cases/1 million females age 15-19
 US and UK studies demonstrated that earlier
screening did NOT decrease cervical cancer rates in
this population.
 Barnholtz-Sloan, 2009; Sasieni, 2009
 If <21 and screened and abnormality detected, follow
guidelines of 21 - 24
Screening 21 - 29
 Every 3 years
 Co-testing with HPV should NOT be performed (HPV
frequent in this population and >90% will
spontaneously clear within 2 yrs)
Screening 30 - 65
 Every 5 yrs
 Co-testing of HPV 16/18
Risk Factors for Continued Annual
Screening
 Hx of CIN2/3/cervical cancer within the past 20 yrs
 HIV infection or immunosuppression (transplant
recipients)
 DES exposure in utero (last used in US >40 yrs ago)
When to stop?
 Age 65 and not at high risk for cervical cancer
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(USPSTF, ACOG, ASCCP)
Discontinuation of screening assumes adequate prior
negative screening
Three consecutive negative cytology results or 2
negative cytology results with (-) co-testing within the
prior 10 yrs with one within 5 yrs
No prior hx of cervical cancer, CIN2/3.
If any present, continue screening for 20 yrs
When to stop?
After hysterectomy (with cervix removal) if no CIN 2/3
or cervical cancer
If CIN 2+, and cervix removed, continue screening of
vaginal cuff for 20 yrs, even if > 65
If hysterectomy and cervix not removed, continue
screening as recommended for age
High Risk HPV Testing
 Use as a co-test in women 30 and older
 Do not use at all in women < 30
 Not a screening test for STDs
 Do not use as a test to determine whether to give HPV
vaccine
Unsatisfactory Cytology
 Repeat cytology in 2 – 4 months is recommended, with
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a negative or unknown HPV result
Triage using reflex HPV testing not recommended
Treatment to resolve atrophy or obscuring
inflammation is acceptable
If 30+ with (+) HPV co-test, repeat cytology in 2-4
months or colposcopy is acceptable.
Colposcopy if 2 consecutive unsatisfactory cytology
results.
Negative Cytology but EC/TZ
Absent/Insufficient
 21 – 29: routine screening is recommended; HPV
testing is unacceptable
 30+: HPV testing preferred. Repeat cytology in 3 years
if not performed. If HPV (-) return to routine.
 If HPV 16 or 18 (+), colposcopy, if (-) then repeat
cytology in 1 yr
 Not associated with an increased incidence of cervical
disease after treatment of high grade disease
>30 Cytology Negative, (+) HPV
 Repeat cytology in 1 year is acceptable
 If repeat is (+) HPV, or ASCUS or worse, then
colposcopy.
 If repeat cytology (-) and HPV (-), then repeat 3 yrs
 Risk of CIN 2+ is small with single HPV (+) and
negative cytology.
 Reflex testing of 16/18 if HPV (+) is acceptable
Women >25 with ASCUS
 Reflex HPV testing is preferred. If neg, then recheck 3
years with co-testing
 (+) HPV- colposcopy with ECC. If no CIN identified,
then recheck pap w co-testing in 12 months
 If ASCUS and no HPV results, repeat cytology at 1 year
is acceptable
 If >65, considered abnormal and should be rechecked
in 12 months
ASCUS with (-)HPV and 3 year f/u
 Risk of CIN 3 if ASCUS and HPV (-): 0.28% (Stoler
2011)
 5 year f/u (no treatment): CIN 3 – 0.54% (Katki 2011)
 Normal cytology control (no HPV testing): risk of CIN
3 at 5 year f/u is 0.36%
ASCUS – new recommendations
 ASCUS and HPV (-)  co-testing in 3 years
 ASCUS and HPV (+)  colposcopy
 ASCH  manage like HSIL  colposcopy
Low-Grade Squamous
Intraepithelial Lesions (LSIL)
 Major determinant in treatment is age
 21 – 24
 HPV status in 25+
 Routine co-testing in 30+
 Here is where reflex co-testing is acceptable
 Reflex testing is NOT recommended in 21 - 24
HSIL in 25+
 Immediate LEEP or colposcopy is acceptable, except in
special populations.
 Diagnostic excisional procedure is recommended
when colposcopy is inadequate EXCEPT pregnancy
 ~60% have CIN 2+ on colposcopically directed bx and
2% have cervical cancer
 5 yr cancer risk is 8%among women aged 30+
ASC-H or HSIL 21 - 24
 Colposcopy
 When CIN 2+ not identified, observation for up to 24
months using BOTH colposcopy and cytology testing
at 6 month intervals is recommended.
 If HSIL persists without identification of CIN 2+, a
diagnostic excision procedure is recommended.
Atypical Glandular Cells
 Colposcopy with ECC, regardless of HPV
 Endometrial biopsy in 35+, or other risk of
endometrial hyperplasia
 May be associated with benign disease (e.g., polyps,
reactive changes), BUT can be due to adenocarcinoma
of the cervix, endometrium, fallopian tube, or ovary
 9 – 38% have significant neoplasia (CIN 2, AIS, or
cancer)
 3 – 17% have invasive cancer
Subsequent Management of AGC
 AGC-NOS: if CIN 2+ not identified, co-testing at 12
and 24 months recommended.
 If both co-test results are neg, repeat co-testing in 3 yrs
 AGC “favor neoplasia” or endocervical AIS: if invasive
disease not identified at initial colposcopy 
diagnostic excisional procedure recommended
Endometrial Cells with Cervical
cytology
 No further evaluation in asymptomatic premenopausal
women
 If postmenopausal, endometrial assessment is
recommended regardless of symptoms.
 No further evaluation with benign glandular cells
following hysterectomy
25+ and colposcopy demonstrates
CIN 1 or less
 Co-testing at 1 yr. If both neg, then age-appropriate
retesting in 3 years recommended.
 If CIN persists for at least 2 years, either continued f/u
or treatment is acceptable.
 A diagnostic excision procedure is recommended if
colposcopic exam is inadequate
25+ after colposcopic evaluation of
ASC-H or HSIL
 If CIN 2 not present on histology, then either
diagnostic excisional procedure or observation with
co-testing at 12 and 24 months are acceptable.
 If any result is abnormal  repeat colposcopy
 If repeat HSIL at either 1 or 2 yr visit  diagnostic
excisional procedure.
21 – 24 with CIN 1 on Biopsy
 Repeat cytology at 12 month intervals until 2
consecutive negative cytology results
 If f/u after an ASC-H or HSIL cytology result,
observation for up to 24 months using BOTH cytology
and colposcopy at 6 month intervals
 If colposcopy is inadequate, or CIN 2+ identified on
ECC, a diagnostic excisional procedure is
recommended
Biopsy Confirmed CIN 2+
 Adequate colposcopy: both excision and ablation are
acceptable, except in special circumstances.
 Ablation is unacceptable if inadequate colposcopy or
CIN 2+ on ECC
 Observation of CIN 2+ with sequential cytology and
colposcopy is unacceptable, except spec. circs
 Prevalence of CIN 3 peaks between 25 – 30 and
progression to cancer usually takes at least 10 years
longer
CIN 2+ in <25
 When a histologic diagnosis of CIN 3 is present, or
colposcopy is inadequate  treatment
 If colposcopic appearance worsens, or HSIL persists for
1 year  repeat biopsy
 If CIN 2+ persists for 2 years  treatment
 After 2 consecutive negative cytologies, an additional
co-test 1 yr later is recommended, then repeat at 3 yrs
CIN in Pregnant Patient
 Colposcopy should have exclusion of invasive cancer as
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its primary goal.
Unless cancer is identified or suspected, treatment of
CIN in pregnancy is CONTRAindicated.
A diagnostic excisional procedure is recommended
only if invasion is suspected.
Initial evaluation of AGC is the same except NO ECC
or endometrial biopsy
Reassess with cytology and colposcopy no sooner than
6 weeks postpartum.
Additional References
 ACOG Practice Bulletin. Management of abnormal
cervical screening test results and cervical cancer
precursors. Number 140, December, 2013
 USPSTF Web site (March, 2012 recommendations):
http://www.uspreventiveservicetaskforce.org/uspstf11/
cervcancer/cervcancerrs.htm#summary
 ASCCP website (algorithms):
http://www.asccp.org/LinkClick.aspx?fileticket=uUG
OqspsCBU%3d&tabid=5964