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

Wright 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

Wright et al NEJM 2003

“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

Self-assessment answers

Objectives

• Review natural history of HPV • Discuss pros and cons of combined cytology and

HPV DNA testing for primary screening• Review management if combined testing done• Highlight utility of HPV DNA testing for

abnormal cytology results• Review use of HPV DNA testing for colposcopy

follow-up