Post on 22-Dec-2015
Clinical Uses of HPV DNA Testing
Shobhina G. Chheda MD MPH
February 1, 2006
No financial disclosures
Objectives
• Review natural history of HPV • Discuss pros and cons of combined cytology and
HPV DNA testing for primary screening• Outline management if combined testing done• Recognize utility of HPV DNA testing for
abnormal cytology results• Review use of HPV DNA testing for colposcopy
follow-up
Anogenital HPV types
• “Low risk” types– 6, 11 (Genital warts)
• “High risk” types (11)
– 16, 18, 31, 33, 45, 56 HPV 16HPV 18HPV 45HPV 33HPV 31other
53%
13%
Munoz et al NEJM 2003
Persistence of HPV infection in women without cervical cancer
Authors No Pts
Mean age yrs
Type of Infection
6 mos 12 mos 24 mos
Woodman 1075 20 incident 24% 4% < 1%
Moscicki 618 20 prevalent 50% 30% 10%
Ho 608 20 incident _ 30% 8%
Ahdieh 439 32 both 47% 36% 19%
Sun 231 34 both 50% 35% 18%
Richardson 635 23 incident _ 62% _
Wright and Cox: Clinical Uses of HPV Testing
% persistent at
“Clearance” ??
• Possible explanations HPV DNA + to – – Immune system activated and completely
eliminates
– Immune system activated and decreases amount of virus shed to undetectable levels
• Prolonged viral latency
Case of LR…
32 year old woman who has had “regular yearly Pap testing” (always normal) comes in for saying she recently saw some ads for a new test for HPV and she would like this done to screen for cervical cancer.
Should you do the HPV test along with her Pap?
Arguments for combined testing
• Supported as option by ACS and ACOG– Age older than 30
• Sensitivity for CIN 2, 3– HPV alone 95-100%– Single conventional Pap 50-90%– Single liquid- based Pap 70-90%
• Extremely high negative predictive value– 0.9888 to 1.000
• If both negative, extend interval to q3 years
Arguments against combined testing
• Specificity CIN 2, 3– HPV alone 80-90%– Single conventional Pap 95%– Single liquid-based Pap 94%
• In women > 30– 5-15% HPV DNA +– 0.5-1% CIN 2,3 or cervical cancer
• Increased anxiety for no reason
Observed outcomes Using HPV DNA Testing andLiquid Based Cytology for Primary Screening
5651 W omen 15-76 years old (m edian age 34)
H P V n e ga tiveN = 1 4 2 (6 0 % )
0 ca se s C IN 2 , 3
H P V po s it iveN = 9 5 (4 0 % )
1 0 case s C IN 2 ,3 (4 .2 % )
6 m o n th fo llo w upC o lo po scop y a nd H P V
N = 2 37
C yto log y N eg a tiveH P V po s it ive
N = 5 42
Clavel et al Br. J Cancer 2001
Arguments against combined testing
• In women > 30 with three negative consecutive Pap tests can space Pap only testing to q 2-3 years
• Cost HPV test - $ 85 …..
• Did we need another test?– Half of cases of cervical cancer (6,000 /yr)
attributable to under screening
Bottom line on combined testing
• Unlikely that changing from cytology alone to combined testing will significantly reduce risk of developing cervical cancer
• May help space testing out for additional group of women – those >30 who have not yet had 3 consecutive
normal Pap tests
Counseling of LR….
How will the test “help” her…
How could the test “harm” her…
Answering her questions about HPV…
Coming soon…..
Results obtained on cytology and HPV DNA testing
↓ ↓ ↓ ↓ ↓ Routine screening
at 3 years
↓
Cytology negative
HPV negative
Cytology ASCUS Cytology > ASCUS Any cytology result Both negative HPV negative HPV negative HPV positive
↓ ↓ ↓ ↓ Routine Rescreen with screening cytology and HPV Colposcopy Colposcopy at 3 years at 12 months
Cytology ASCUS
HPV positive
Cytology negative
HPV positive
Repeat both tests
at 6 – 12 months
Cytology>ASCUS
any HPV result
Cytology ASCUS
HPV negative
Repeat cytology
at 12 months Colposcopy Colposcopy
Routine screening
at 3 years
Wright et al. Obst Gynec 2004.
Use of HPV DNA test
• Management of ASCUS- “Reflex” HPV test– Run on same sample-liquid based test
– Run on second sample collected initially
• Management of LSIL– Usually do not* order HPV test on same sample
– Adolescent- test at 12 months
– Low- risk post-menopausal*- test at 12 months
• If HPV + send for colposcopy
Use of HPV DNA test
• Colposcopy negative or CIN 1 follow-up– Single colposcopy can miss 1/3 of CIN 2,3
– Test at 12 months if initial cytology• ASCUS
• LSIL
• ASC-H
– If HPV + repeat colposcopy
• Post-treatment CIN 2, 3 follow-up – Test at 6 months
Do not use: HPV DNA test
• STI screening
• Men
• Women less than 30 for screening
• Cannot use to space interval of screening in immunosuppressed women