Clinical Uses of HPV DNA Testing

1. Clinical Uses of HPV DNA Testing Shobhina G. Chheda MD MPH February 1, 2006 No financial disclosures

2. 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

3. Anogenital HPV types • “Low risk” types • 6, 11 (Genital warts) • “High risk” types (11) • 16, 18, 31, 33, 45, 56 53% 13% Munoz et al NEJM 2003

4. Wright et al NEJM 2003

5. Persistence of HPV infection in women without cervical cancer % persistent at Wright and Cox: Clinical Uses of HPV Testing

6. Wright et al NEJM 2003

7. “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

8. 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?

11. 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

12. 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

13. Clavel et al Br. J Cancer 2001

14. 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

15. 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

16. Counseling of LR…. How will the test “help” her… How could the test “harm” her… Answering her questions about HPV… Coming soon…..

17. Results obtained on cytology and HPV DNA testing Wright et al. Obst Gynec 2004.

18. 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

19. 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

20. 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

21. Self-assessment answers

22. 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