Cervical cancer and genital human
papillomaviruses (HPV)
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
•
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
KL Irwin1, D Montaño2, D Kasprzyk2, L Carlin2, C Freeman2, R
Barnes1, N Jain1
1
U.S. Centers for Disease Control and Prevention, Atlanta, Georgia
USA
2
Battelle Memorial Institute, Seattle, Washington, USA
Indication 1:
HPV testing to manage patients with
abnormal Pap results
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
• 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.
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 Æ
recommend prompt colposcopy
– HPV-uninfected women = low risk of developing CIN Æ
recommend repeat Pap test
•
HPV tests not recommended for higher grade Pap results
because colposcopy is advised regardless of HPV test results
1
Indication 2:
HPV test as Pap test adjunct
to guide follow-up Pap interval
2004 national survey of US clinicians:
Selected questions
•
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 screen women aged 30+:
•
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?
– 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 Æ repeat
Pap test and HPV test in 6-12 months
– If HPV test negative = low risk of progression to CIN Æ 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.
Clinician survey methods
Survey Disposition
•
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
Adjusted response rate by specialty
Midlevel provider
%
Physician
%
Nurse midwives
Nurse practitioners
Physician assistant
95
96
86
Adolescent med
Ob/Gyn
Family/Gen practice
Internal med
79
81
68
59
5386 surveys mailed
Overall response rate after adjusting for
respondents who were deceased,
retired, ineligible, or did not have
current address = 82%
5386 Surveys mailed
746 Refused or no response
736 Retired or ineligible
565 Undeliverable or
deceased
3339 Completed surveys
Characteristics of Pap test providers
(n=2980)
Value
Range (%)
46
16
(32-99)
(11-21)
74
78
479
53
46
(37-87)
(58-92)
(110-1397)
(10-158)
(20-98)
67
68
52
(59-100)
(56-71)
(33-67)
Clinician characteristics:
• Female (%)
• Mean years in practice
Practice characteristics:
• Practice in private office setting (%)
• Use liquid-based Pap method (%)
• Mean number Pap tests last yr
• Mean number abnormal Paps last yr
• Have on-site colposcopy (%)
Patient characteristics:
• Mean % patients who are female
• Mean % patients who are white
• Mean % patients private insured
2
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
– Their clinical specialty organization
– Centers for Disease Control and Prevention
– American Cancer Society
%
73
78
63
58
•
< 50% reported using guidelines or materials of:
– US Preventive Services Task Force
– American Society for Colposcopy & Cervical
Pathology
– HPV test manufacturer
– Health plans or insurance companies
%
46
40
36
23
HPV test use by type of
screening Pap test abnormality*
•
•
•
Pap test abnormality
•
•
•
•
Higher grade results**:
Atypical squamous cells of
undetermined significance –
cannot exclude high grade lesion**
79
(72-84)
•
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.
•
100
90
80
70
60
50
40
30
20
10
0
OB/GYN
OB/GYN
40
35
30
25
20
15
10
5
CNM
NP
FP
PA
IM
ADOL
CNM
NP
FP
PA
IM
ADOL
Total
Relation of HPV test results on
colposcopy or followup Pap advice
for women with ASC-US Pap results
reporting usual/always use
%
range (%)*
Borderline result “ASC-US”
98
(96-100)
Percent who report ever using HPV
tests as an adjunct to Pap tests
by specialty
% Respondents
% Using test
•
Percent reporting ever using HPV
tests for patients with Pap test
abnormalities of any type
100
80
% who
usually
advise
follow-up
procedure
60
40
20
0
Colposcopy Pap test
Colposcopy Pap test
HPV test positive
HPV test negative
Percentage who reported usually/always
using HPV tests as an adjunct to Pap tests
by patient age
Percentage
Total
0
37.3
10
20
30
40
Sexually-active
*Women < 30
26
19.6 19.3
20.8
15.7
Sexually-active
Women >= 30
10.2 11.8
*Indication not endorsed by national guidelines
0
Specialty
3
Summary
Percentage who reported usually/always
using HPV tests as an adjunct to Pap tests
by patient age
Percentage
0
20
40
60
80
•
Most commonly cited guidelines are credible, noncommercial, and consistent with recent scientific evidence
•
More than half of Pap test providers use HPV tests for ASCUS Pap results (a recommended option), especially:
100
– Obstetrician/gynecologists and nurse midwives
– Clinicians with high volume of Paps and abnormal Pap tests
– Clinicians with on-site colposcopy
Sexually-active
*Women < 30
•
Sexually-active
Women >= 30
•
*Indication not endorsed by national guidelines
•
•
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)
Study strengths and limitations
Recommendations
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
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
•
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
Patient counseling messages used by
2980 clinicians providing Pap tests
Message
•
When collecting Paps, I usually/always:
•
•
•
Address methods to prevent cancer
Discuss HPV as cancer risk factor
Discuss HPV prevention
%
Range (%)
49
43
43
(43-72)
(32-66)
(30-79)
For patients w/ HPV+ test or HPV-related Pap, I usually/always say:
•
•
•
•
•
•
Virus is sexually transmitted
Patient could transmit virus to partners
HPV is common in sexually active persons
Monogamy/↓ partner # can prevent transmission
Condom use can prevent transmission
Abstinence can prevent transmission
95
91
92
79
84
41
(88-99)
(83-97)
(76-93)
(70-86)
(81-95)
(30-63)
4
Key issues when addressing patients
with positive HPV tests or HPV-related
Pap results
•
Addressing HPV would:
Reported use of liquid-based cytology
(LBC) and Conventional cytology
LBC and
Conventional Pap
%
– 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
Deal with emotional or relationship issues
Get enough reimbursement to counsel patients
Find time to counsel/educate patients
When using to manage abnormal Pap results:
–
–
–
–
•
Seek patients consent for test
Tell patients you are ordering
Explain purpose of test as relates to Pap
Explain HPV test detects STD
Seek patients consent for test
Tell patients you are ordering
Explain purpose of test in relation to Pap
Explain HPV test detects STD
21.1
Conventional only
%
85
73
74
54
0
20
40
60
80
% Respondents
NON-NBCCEDP
Summary:
HPV test consent, notification, and
counseling practices
%
28
48
58
59
•
•
•
When ordering test as adjunct to screening Pap test: %
–
–
–
–
67.6
LBC only
Usual HPV test consent practices
among 2680 Pap test providers
•
11.3
36
59
63
64
•
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
5