2005 AcademyHealth Annual Research Meeting

1. Cervical cancer screening practices in the U. S. since the release of national guidelines on genital human papillomavirus (HPV) testing:Results of a national clinician survey,2004 2005 AcademyHealth Annual Research Meeting KL Irwin1, D Montaño2, D Kasprzyk2, L Carlin2, C Freeman2, R Barnes1, N Jain1 1U.S. Centers for Disease Control and Prevention, Atlanta, Georgia USA 2Battelle Memorial Institute, Seattle, Washington, USA

2. Cervical cancer and genital human papillomaviruses (HPV) • Genital HPV are very common sexually transmitted viruses • ~ 6 million new infections per year in US • ~ 20 million Americans are currently infected • Most infections are transient, asymptomatic, and clear without medical intervention. • Persistent infection with oncogenic HPV types may cause: • Cervical cancer precursor lesions or Cervical Intraepithelial Neoplasia (CIN) • Invasive cervical cancer • In 2004, US women experienced: • ~ 4000 deaths from cervical cancer • > 3 million abnormal Pap tests, most HPV-related • > $1 billion in Pap test screening, follow up, and treatment costs

3. New tests for oncogenic types of HPV • In the late 1990s, highly sensitive and specific DNA tests for oncogenic HPV were developed. • Use of new liquid-based Pap test methods facilitates collection of HPV test specimens. • FDA recently approved HPV tests for various reasons, including • managing patients with abnormal Pap tests • an adjunct to Pap tests to screen women aged 30+ for cervical cancer

4. Indication 1:HPV testing to manage patients with abnormal Pap results • Women with abnormal Pap tests benefit from colposcopy = magnified visualization of cervix • requires a speculum-aided pelvic examination, special equipment, and trained colposcopist • Permits cervical biopsy that provide pathologic diagnosis that determines treatment • Colposcopy is a costly, painful procedure that is in short-supply in the U.S., especially in communities with highest cervical cancer incidence.

6. Indication 1 (continued) • In 2000, FDA approved HPV tests to guide colposcopy triage of patients with the most common Pap test abnormality ASC-US (Atypical Squamous Cells, Undetermined Significance) • In 2001, several organizations issued guidelines endorsing HPV tests as an option to guide such triage, including: • American College of Obstetricians and Gynecologists • Centers for Disease Control and Prevention • American Cancer Society • With this option, one orders HPV test if Pap result is ASC-US: • HPV-infected women = high risk of developing CIN  recommend prompt colposcopy • HPV-uninfected women = low risk of developing CIN  recommend repeat Pap test • HPV tests not recommended for higher grade Pap results because colposcopy is advised regardless of HPV test results

7. Indication 2:HPV test as Pap test adjunct to guide follow-up Pap interval • In 2003, the FDA approved HPV tests as an adjunct to Pap tests to screen women aged 30+ to guide optimal follow up Pap test intervals because infection in women aged 30+ often represents persistent infection that increases risk of CIN. • In 2003, two organizations issued guidelines that endorsed HPV tests as an option to screenwomen aged 30+: • American Cancer Society • American College of Obstetricians and Gynecologists • This option would advise for women with normal Pap tests: • If HPV test positive = high risk of progression to CIN  repeat Pap test and HPV test in 6-12 months • If HPV test negative = low risk of progression to CIN  less frequent follow up Pap screening intervals (every 3 years) • This option could reduce frequent screening of women at low risk for developing HPV-related abnormalities and enhance follow up of women at high risk for these abnormalities.

8. 2004 national survey of US clinicians:Selected questions • What guidelines are being used to guide cancer screening practices and management of abnormal Pap tests? • How are HPV DNA tests being used for: • managing patients with abnormal Pap tests • cervical cancer screening • How are HPV test results influencing colposcopy and Pap test follow up practices? • What are patient notification and consent when ordering HPV tests? • How do HPV test use and test results influence patient counseling and education messages?

9. Clinician survey methods • Express mailed surveys to 5386 primary care clinicians in specialties that commonly provide Pap testing. • Nationally-representative random samples (n=760-826) drawn from national clinician registries of: • Physicians: Midlevel providers: • Family/general practice Physician assistants • Adolescent medicine Certified nurse midwives • Internal medicine Nurse practitioners • Obstetrics/gynecology • Cover letter noted results will inform new clinician training and decision supports tools and patient education materials • Survey required 20-40 minutes, $50 cash sent with first mailing • Analyses weighted to account for differences by clinical specialty in sampling and non-response

10. Survey Disposition

11. Midlevel provider % Nurse midwives 95 Nurse practitioners 96 Physician assistant 86 5386 surveys mailed Overall response rate after adjusting for respondents who were deceased, retired, ineligible, or did not have current address = 82% Physician % Adolescent med 79 Ob/Gyn 81 Family/Gen practice 68 Internal med 59 Adjusted response rate by specialty

12. Characteristics of Pap test providers(n=2980) Value Range (%) Clinician characteristics: • Female (%) 46 (32-99) • Mean years in practice 16 (11-21) Practice characteristics: • Practice in private office setting (%) 74 (37-87) • Use liquid-based Pap method (%) 78 (58-92) • Mean number Pap tests last yr 479 (110-1397) • Mean number abnormal Paps last yr 53 (10-158) • Have on-site colposcopy (%) 46 (20-98) Patient characteristics: • Mean % patients who are female 67 (59-100) • Mean % patients who are white 68 (56-71) • Mean % patients private insured 52 (33-67)

13. Sources used to guide cervical cancer screening or abnormal Pap management decisions among 2930 Pap test providers • >50% reported using guidelines or materials of: % • American College of Obstetrics/Gynecology 73 • Their clinical specialty organization 78 • Centers for Disease Control and Prevention 63 • American Cancer Society 58 • <50% reported using guidelines or materials of: % • US Preventive Services Task Force 46 • American Society for Colposcopy & Cervical Pathology 40 • HPV test manufacturer 36 • Health plans or insurance companies 23

14. Percent reporting ever using HPV tests for patients with Pap test abnormalities of any type

15. HPV test use by type of screening Pap test abnormality* • Pap test abnormality reporting usual/always use • % range (%)* • Borderline result “ASC-US” 98 (96-100) • Higher grade results**: • Atypical squamous cells of 79 (72-84) • undetermined significance – • cannot exclude high grade lesion** • Low grade intraepithelial neoplasia** 63 (36-82) • High grade intraepithelial neoplasia** 61 (31-78) • * Among clinicians reporting HPV tests for any borderline or abnormal Pap test result. Range across 7 clinical specialties. • **This use NOT approved by FDA or recommended by guidelines of U. S. clinical organizations. Internal and adolescent medicine physicians most commonly reported use for high grade lesions.

16. Relation of HPV test results on colposcopy or followup Pap advice for women with ASC-US Pap results % who usually advise follow-up procedure Colposcopy Pap test Colposcopy Pap test HPV test positive HPV test negative

17. Percent who report ever using HPV tests as an adjunct to Pap tests by specialty

18. Percentage who reported usually/always using HPV tests as an adjunct to Pap tests by patient age *Indication not endorsed by national guidelines

19. Percentage who reported usually/always using HPV tests as an adjunct to Pap tests by patient age *Indication not endorsed by national guidelines

20. Summary • Most commonly cited guidelines are credible, non-commercial, and consistent with recent scientific evidence • More than half of Pap test providers use HPV tests for ASC-US Pap results (a recommended option), especially: • Obstetrician/gynecologists and nurse midwives • Clinicians with high volume of Paps and abnormal Pap tests • Clinicians with on-site colposcopy • Colposcopy is more likely to be recommended to women with positive HPV tests as intended by guidelines • However, many report using HPV tests for patients with higher grade Pap abnormalities which is not recommended • Few report usually using HPV tests as adjunct to Pap tests in women 30+ (a recommended option) • However, such HPV test use is more common in women < 30 (not-recommended) than women 30+ (recommended)

21. Study strengths and limitations STRENGTHS: • Large sample size with high overall response rate (82%) • Stratified sampling design and weighting yielded more generalizable estimates within and across specialty • Included midlevel providers who provide much cervical cancer screening but are often overlooked in surveys LIMITATIONS: • Reported practices may not reflect actual practices • Survey did not determine: • If use of HPV tests resulted in more appropriate use of colposcopy or follow up Pap intervals • reasons HPV tests used for non-recommended reasons

22. Recommendations • Interventions are needed to promote HPV testing practices that are consistent with national guidelines to avoid unnecessary: • patient anxiety, stigma, or psychosocial burden due to STD • counseling burden by clinicians • HPV testing costs • Interventions should be designed with input of key stakeholders: • national organizations that issue screening guidelines • laboratories • health insurers, health plans, and health care purchasers • HPV and Pap test manufacturers • women eligible for cervical cancer screening • CDC, in collaboration with other organizations is: • Updating clinical training and clinical decision support tools • Disseminating materials using print, web, and 2005 webcast • Updating patient and public education web and print materials to promote HPV test demand consistent with guidelines

23. CDC sponsored webcast to train U.S. clinicians about HPV and cervical cancer Date: August 9, 2005 Time: 1-2 pm Eastern Time Audience: Primary care clinicians CME and CEU credits available For more information: www.phppo.cdc.gov/PHTN/HPV-05

24. Patient counseling messages used by 2980 clinicians providing Pap tests Message % Range (%) • When collecting Paps, I usually/always: • Address methods to prevent cancer 49 (43-72) • Discuss HPV as cancer risk factor 43 (32-66) • Discuss HPV prevention 43 (30-79) For patients w/ HPV+ test or HPV-related Pap, I usually/always say: • Virus is sexually transmitted 95 (88-99) • Patient could transmit virus to partners 91 (83-97) • HPV is common in sexually active persons 92 (76-93) • Monogamy/↓ partner # can prevent transmission 79 (70-86) • Condom use can prevent transmission 84 (81-95) • Abstinence can prevent transmission 41 (30-63)

25. Key issues when addressing patients with positive HPV tests or HPV-related Pap results • Addressing HPV would: % • Increase likelihood patient would return for repeat Pap 87 • Assure patients they are getting complete information 83 • Raise patient concerns about partner fidelity 68 • It is somewhat or quite problematic to: % • Indicate when/from whom infection was acquired 85 • Deal with emotional or relationship issues 73 • Get enough reimbursement to counsel patients 74 • Find time to counsel/educate patients 54

26. Reported use of liquid-based cytology (LBC) and Conventional cytology

27. Usual HPV test consent practices among 2680 Pap test providers • When using to manage abnormal Pap results: % • Seek patients consent for test 28 • Tell patients you are ordering 48 • Explain purpose of test as relates to Pap 58 • Explain HPV test detects STD 59 • When ordering test as adjunct to screening Pap test: % • Seek patients consent for test 36 • Tell patients you are ordering 59 • Explain purpose of test in relation to Pap 63 • Explain HPV test detects STD 64

28. Summary: HPV test consent, notification, and counseling practices • About one third explicitly report seeking consent for HPV testing • About half report notifying patients when they are ordering HPV tests • About two-thirds report telling patients that test detects sexually transmitted infection • However, more than half report telling patients about sexually transmitted HPV when: • collecting Pap tests • notifying patients with positive HPV tests or HPV-related Pap abnormalities