For each woman, there’s a strategy
The Roche Cervical Cancer Screening Portfolio helps
protect her from cancer and from overtreatment
Today’s screening strategies must balance
maximizing benefits with minimizing
potential harm for all women
Achieving the goals of cervical cancer screening has remained elusive
• Identifying as many women as possible at risk of precancer
• Avoiding unnecessary interventions for HPV positive women by sorting them into two groups:
- Those at greatest risk for having high-grade disease now or developing it in the future
- Those at lower risk and having HPV infections that are likely to resolve on their own
Current screening strategies are not enough
• Cytology has high specificity but low sensitivity, resulting in missed disease in women1
• Up to 1/3 of cervical cancers occur in screened women with normal Pap cytology2,3
• Pooled hrHPV testing has high sensitivity but low specificity, resulting in over-referral of healthy
women who may not need colposcopy4
- These false-positives have an unnecessary adverse psychosocial impact on women,5 and may
result in unnecessary interventions that place a large financial burden on the healthcare system
Addressing the conflicting challenges requires the right triage strategy
• First, use a test with high sensitivity and negative predictive value (NPV) to determine which women
can safely return to routine screening
• Second, use tests that have high specificity and positive predictive value (PPV) to determine which
women need further evaluation now and which women can be managed over time
The clinical dilemma with HPV positive
women is to determine who would
benefit most from colposcopy
and who may be spared intervention.4
hrHPV = high-risk human papillomavirus
The patients described in this brochure are not
actual patients, but rather are representative of
patient scenarios often seen in clinical practice.
Which strategy is right for her?
Roche brings clarity to screening,
diagnosis and management
The comprehensive strategy for diagnostic screening
With a portfolio of screening, triage and precancer diagnostic tools, Roche
helps enable better patient outcomes by identifying women who can return
safely to routine screening, reducing the number of colposcopies per CIN3
cases detected, as well as identifying more disease than current strategies.6-9
1. Identify women who can safely return
to routine screening, those who need
additional testing and those who need
immediate management
Stratifies women according to risk, based on
pooled hrHPV and HPV 16/18 genotyping results6
2. Identify
HPV positive
women who
require immediate
management
Helps identify women
with transforming
lesions (p16/Ki-67
positive) who need
colposcopy7,8
HPV Test
3. Increase diagnostic accuracy for high-grade disease
Helps diagnose and confirm the presence or absence of ≥CIN2
lesions (p16 positive) in biopsies obtained during colposcopies9
Testing for HPV 16 and HPV 18 brings clarity
Identify women at greatest risk
The cobas® HPV Test is the only clinically validated,
CE-marked and FDA-approved* test that simultaneously
provides pooled results on known “high-risk” genotypes
and individual results on the 2 highest-risk genotypes,
HPV 16 and HPV 18, giving 3 results in just 1 test.
The cobas® HPV Test adds greater specificity
to screening strategies than pooled hrHPV alone
• In a 10-year study of women with normal cytology,
women HPV 16 positive or HPV 18 positive were more
likely to have ≥CIN3 than women who were positive
for other pooled HPV genotypes10
• Women HPV 16 positive and/or HPV 18 positive are at
increased risk of ≥CIN3 even if they have normal
baseline and repeat cytologies11
Primary screening with the cobas HPV Test
(Not approved in the US or Canada)
®
HPV 16 and HPV 18 cause 70% of cervical cancers and
are the 2 most prevalent oncogenic HPV types in both
squamous cell carcinoma and adenocarcinoma.12
HPV 16 causes
55%–60% of
cervical cancer13
16
18
HPV 18 causes a
significant proportion
of adenocarcinomas,
which are hard to
detect by cytology12
• When used in primary screening, HPV with 16/18
genotyping was more efficient than the current
standard of care, significantly reducing the number of
colposcopies necessary per ≥CIN3 detected4
The optimal primary screening strategy focuses medical
attention on women with genotypes HPV 16 or 18, and
triages other high-risk HPV genotypes.4
The landmark ATHENA study provided clinical evidence to
support the US guidelines in recognizing the benefits of
identifying HPV 16 or HPV 16/18.13
Maria, 51
Screening result:
cobas® HPV
genotype 16 positive
Management: Colposcopy
In cervical cancer screening
Help protect women from cervical
cancer and from overtreatment
• In the ATHENA study, the cobas® HPV Test found 92%
of cases of ≥CIN3 in the overall population compared
to 53% found by cytology1
• Nearly 1 in 7 women with normal cytology (NILM) who
were HPV 16 positive actually had high-grade cervical
disease that was missed by cytology14
The cobas® HPV Test helps protect women from
overtreatment
• The cobas® HPV Test identifies all high-risk HPV
genotypes as well as individual results for the most
aggressive HPV genotypes 16 & 186
- Protects healthy women from unnecessary
intervention, allowing them to return to routine
screening if results are negative
Absolute risk of ≥CIN2 stratified by hrHPV status in the ATHENA
14
Absolute
risk of ≥ CIN2 stratified by hrHPV status
NILM population
in the ATHENA NILM population*1
Estimated absolute risk (%)
Uncover disease that is missed by cytology alone
20
Stratified cobas®
HPV Test positive result
15
13.6
14 pooled cobas ®
HPV Test result
10
5
6.1
Cytology
result
1.2
0.8
NILM
hrHPV−
0
hrHPV+
7.0
4.6
12 hrHPV+ HPV16+ HPV18+
Absolute risk measurements are estimates based on raw study data.
- Identifies women who need immediate intervention
if HPV 16/18 positive
HPV DNA-based screening reduces the incidence of cervical
cancer within 4 to 5 years compared to cytology-based
screens.15,16
Anna, 38
Screening result:
cobas® HPV negative
Management: Return to
routine screening interval
The patients described in this brochure are not actual patients, but rather are representative of patient scenarios often seen in clinical practice.
*The cobas® HPV Test is not approved for primary screening in the US.
ATHENA = Addressing THE Need for Advanced HPV Diagnostics; CE-marked = verification that products meet European Union safety, health,
or environmental requirements; FDA = US Food and Drug Administration; NILM = negative for intraepithelial lesion or malignancy.
In cervical cancer screening
CINtec® PLUS, an advanced
biomarker combination
In cervical biopsy diagnosis
CINtec® p16 Histology
sets a new standard for
diagnostic excellence
The CINtec® PLUS immunocytochemistry assay is for the simultaneous qualitative
detection of the p16INK4a and Ki-67 proteins in cervical cytology preparations.17
• Identifies underlying high-grade cervical disease
• Helps identify women with transforming lesions (p16/Ki-67 positive) who
need colposcopy
Identify HPV positive women requiring immediate management
• Demonstrates high sensitivity (>90%) for the detection of established
high-grade disease in Pap negative, HPV positive women ≥30y7
• Provides high specificity, enabling triage of 75% of women back
to routine testing7
• May reduce the number of unnecessary colposcopies by up to 50%8
The CINtec® p16 Histology product
is an immunohistochemistry assay for the
qualitative detection of the p16INK4a protein
on slides prepared from formalin-fixed,
paraffin-embedded cervical biopsies.17
Challenges with diagnostic
accuracy exist
• It is important to distinguish between
high-grade CIN and its morphologic mimics
to avoid overtreatment of false-positive cases
and undertreatment of false-negative cases9
• Histological assessment of cervical dysplasia
is complicated by interobserver variability18
• Lesions may be missed due to small
representation or severe inflammation19
Significantly increased diagnostic
accuracy with the CINtec® p16 Histology
product9
• 13% increase for detecting ≥CIN2
without a loss in specificity9
• 45% reduction in false-negative
interpretations9
• 30% overall increase in interobserver
agreement for diagnosing ≥CIN29
Brigitte, 31
Screening results:
cobas® HPV other
HR positive, genotypes
16/18 negative
CINtec® PLUS negative
Management: Monitor
through regular follow-up
*Not all products and uses are available in all countries. Please refer to the package insert for
applicable intended uses for each individual product.
H&E = Hematoxylin and eosin [stain].
H&E
K = 0.58
H&E + p16
K = 0.76
Identify more occult lesions19
• 22% increase in identification of CIN lesions
from H&E biopsies initially diagnosed as
negative19
s
or
In cervical cancer screening
CINtec® PLUS provides high sensitivity
and high specificity in a single test
• Provides an option for immediate management
of women testing Pap negative/HPV positive especially
when HPV 16/18 results are negative or unknown7
The Wolfsburg Study
(n=425 women tested Pap negative but hrHPV positive)7
• The first tool for efficient management of women with
LSIL cytology8
CINtec® PLUS
Sensitivity in Pap Negative/hrHPV Positive Women ≥30y
≥CIN2
≥CIN3
92%
96%
Biopsy-confirmed cases
A positive test result with CINtec® PLUS
is an indicator for women to be referred
for colposcopy.
≥CIN2 (n=37); ≥CIN3 (n=28)
Rates of Positivity in Pap Negative/hrHPV Positive Women ≥30y
CINtec® PLUS
Negative cases
75%
25%
Positive cases
CINtec® PLUS in LSIL Cytology: Data from EEMAPS®8
(n=137 biopsy-confirmed cases of ≥CIN2)
94%
Sensitivity
Specificity
96%
68%
19%
52%
Colposcopy
referrals
86%
CINtec® PLUS
Pooled hrHPV
Susanna, 34
Screening results:
cobas® HPV other
HR positive, genotypes
16/18 negative
CINtec® PLUS positive
Management: Colposcopy
The patients described in this brochure are not actual patients, but rather are representative of patient scenarios often seen in clinical practice.
EEMAPS = European Equivocal or Mildly Abnormal Pap Cytology Study; LSIL = Low-grade squamous intraepithelial lesion.
Help protect women from cervical
cancer and from overtreatment
With the goal of bringing greater clarity to the
continuum of patient management, Roche helps put
the right information in your hands with solutions that
address the unmet need in cervical cancer screening.
HPV Test
Identify women who can safely return to routine screening,
those who need additional testing and those who need
immediate management
Stratifies women according to risk, based on pooled hrHPV and HPV
16/18 genotyping results6
Identify HPV positive women who require immediate
management
Helps identify women with transforming lesions (p16/Ki-67 positive)
who need colposcopy7,8
Increase diagnostic accuracy for high-grade disease
Helps confirm the presence or absence of ≥CIN2 lesions in biopsies9
REFERENCES:
COBAS and CINtec are trademarks of Roche. All other trademarks are the property of their respective owners.
© 2013 Roche Molecular Systems, Inc.
Roche Molecular Diagnostics
4300 Hacienda Drive
Pleasanton, CA 94588
USA
http://molecular.roche.com
07071841001  0513 - 5. WW
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and older: a subanalysis of the ATHENA study [published online August 23, 2011]. Lancet Oncol. 2011;12(9):880-890. 2. Leyden WA, Manos MM, Geiger AM, et al. Cervical cancer in women with
comprehensive health care access: attributable factors in the screening process. J Natl Cancer Inst. 2005;97:675-683. 3. Andrae B, Kemetli L, Sparén P, et al. Screening-preventable cervical cancer risks:
evidence from a nationwide audit in Sweden. J Natl Cancer Inst. 2008;100(9):622-629. 4. Cox JT, Castle PE, Behrens CM, et al. Comparison of cervical cancer screening strategies incorporating different
combinations of cytology, HPV testing and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol. 2013;208(3):184.e1-184.e11. 5. Gray NM, Sharp L, Cotton SC, et al.
Psychological effects of a low-grade abnormal cervical smear test result: anxiety and associated factors. B J Cancer. 2006:94(9):1253-1262. 6. cobas® HPV test [package insert, US]: Branchburg, NJ.
Roche Molecular Systems, Inc; 2011;135:468-475. 7. Petry KU, Schmidt D, Scherbring S, et al. Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 dual-stained
cytology. Gynecol Oncol. 2011;121(3):505-509. 8. Schmidt D, Bergeron C, Denton KJ, et al; European CINtec Cytology Study Group. p16/Ki-67 dual-stain cytology in the triage of ASCUS and LSIL
Papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study. Cancer Cytopathol. 2011;119(3):158-166. 9. Bergeron C, Ordi J, Schmidt D, et al; European
CINtec Histology Study Group. Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia. Am J Clin Pathol. 2010;133(3):395-406. 10. Khan
MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing
in clinical practice. J Natl Cancer Inst. 2005;97(14):1072-1079. 11. Berkhof J, Bulkmans NWJ, Bleeker MCG, et al. Human papillomavirus type–specific 18-month risk of high-grade cervical intraepithelial
neoplasia in women with a normal or borderline/mildly dyskaryotic smear. Cancer Epidemiol Biomarkers Prev. 2006;15(7):1268-1273. 12. Herzog TJ, Monk BJ. Reducing the burden of glandular
carcinomas of the uterine cervix. Am J Obstet Gynecol. 2007;197(6):566-571. 13. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical
Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012;137(4):516-542. 14. Wright TC Jr, Stoler
MH, Sharma A, Zhang G, Behrens C, Wright TL; ATHENA (Addressing THE Need for Advanced HPV Diagnostics) Study Group. Evaluation of HPV-16 and HPV-18 genotyping for the triage of women
with high-risk HPV+ cytology-negative results. Am J Clin Pathol. 2011;136:578-586. 15. Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection of high-grade cervical
intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012;13:78-88. 16. Ronco G, Giorgi-Rossi P, Carozzi F, et al; the New Technologies for
Cervical Cancer screening (NTCC) Working Group. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised
controlled trial. Lancet Oncol. 2010;11(3):249-257. 17. CINtec®PLUS IFU. 18. Galgano MT, Castle PE, Atkins KA, et al. Using biomarkers as objective standards in the diagnosis of cervical biopsies.
Am J Surg Pathol 2010;34(8):1077-1087. 19. Ordi J, Garcia S, del Pino M, et al. p16INK4a immunostaining identifies occult CIN lesions in HPV-positive women. Int J Gynecol Pathol 2009;28(1):90-97.