Beruflich Dokumente
Kultur Dokumente
Detection in Cervical
Cancer
Bambang Dwipoyono
SMF ginekologi onkologi
RS Kanker Dharmais
SURGERY RADIOTHERAPY
Clear difference
between
developed and
developing world
Source: Freeman HP, Wingrove BK. Excess cervical cancer mortality: A marker for low access to
health care in poor communities. Rockville, MD:Nasional,
Seminar National Dharmais
Cancer Institute,
9 Center to Reduce Cancer
11
Health Disparities; 2005. Report: NIH Pub. No. 05-5282. 2010
Nopember
Cervical cancer: What is the chance
of survival after treatment?
FIGO Stage 5-Year Survival
Stage I 81-96%
Stage II 65-87%
Main focus on
Developing & improving cancer therapies
Carcinogenesis
Early detection
PRIMARY PREVENTION
Prevention of disease by
controlling risk factors (e.g.,
non-smoking promotion)
Nutritional
Science
Cellular and
Molecular Infectious
Biology Disease
Surgery Public Health Epidemiology
Policy
Behavioral Imaging/
Medicine Screening
Pharmacology
Uncommon
cancers
difficult to 5%-10%
detect
Sources:NIH Consensus Conference
Janerich, Connecticut 9%-12%
Sung, California Seminar Nasional, Dharmais 9 Nopember 2010 22
Pathogenesis of Cervical
Cancer
Persistent Cellular
HPV Infection
HPV Infection Dysregulation
High-Grade CIN
Immunologic
Factors
Invasive Cancer
Co- carcinogens
Seminar Nasional, Dharmais 9 Nopember 2010 23
Continuum of Care for Cervical
Cancer Control
35
Liquid-Based Cytology (LBC)
Ronco G. et al. BMJ 2007
• Randomised controlled trial with >45,000 women
randomised to LBC or conventional cytology within
regional organised screening programmes in the
north of Italy
• Liquid based cytology is not statistically significantly
different from the conventional Pap in terms of
sensitivity for detection of CIN2+
36
Liquid-Based Cytology (LBC)
Arbyn M. et al. Obstet Gynecol 2008
• Systematic review of 9 studies comparing LBC to
the conventional Pap in which the results were
based on histological outcomes
• LBC is neither more sensitive nor more specific
for the detection of high-grade CIN compared with
the conventional Pap test
37
Large, prospective, randomised controlled trials (RCTs)
HPV Testing for Primary Screening
Study Country N Age HPV Test Cytology Main Study Outcomes
Finnish RPHT Finland 200,000 25-65 HC2 Pap smear Cumulative incidence of
CIN2+ after initial screen
ing
Swedescreen Sweden 12,527 32-38 PCR (GP5 Pap smear Comparative prevalence
+/6+) of CIN2+ at the exit scree
n
POBASCAM The Nether 44,102 30-60 PCR (GP5 Pap smear Proportion of CIN3+ foun
-lands +/6+) d from recruitment to exi
t screen
NTCC Italy 95,000 25-60 HC2 Pap & LBC Cumulative prevalence o
f CIN2+ up to and includi
ng exit screen
38
HPV Testing for Primary Screening
Ronco G et al. JNCI 2008
•Randomised controlled trial with 90,000 women
randomised to conventional Pap or HPV testing (HC2)
with immediate referral to colposcopy if positive for
HPV or low-grade cytology (age 36-60)
• Positive threshold – 1.0pg/mL / CIN3+
• Relative sensitivity 1.52 (1.06 to 2.19)
• Relative PPV 0.63 (0.44 to 0.89)
• Positive threshold – 2.0pg/mL / CIN3+
• Relative sensitivity 1.50 (1.04 to 2.16)
• Relative PPV 0.81 (0.56 to 1.15)
39
HPV Testing for Primary Screening
Bulkmans et al. BJC 2005
•Randomised controlled trial with >44,000 women
randomised to conventional Pap or HPV testing (in-
house PCR) conducted within the routine Dutch
cervical cancer screening programme with cytology
triage (aged 29-56 years):
• More sensitive for CIN3+ (92.9 vs 64.3%)
• Equivalent specificity (96.7 vs 95.1%)
• Higher PPV (14.6 vs 7.3%)
40
HPV Testing for Primary Screening
Conclusions from the data:
•HPV testing can increase the sensitivity for CIN3+
by about 50% over that of high-quality conventional
Pap cytology
•With cytology triage of women testing HPV positive,
the specificity and PPV are equivalent to that of high-
quality cytology
•HPV testing will allow the screening interval to be
safely lengthened
41
HPV Testing for Primary Screening
Other aspects to consider:
•Produces a non-subjective + or – result which simplifies
training and QA procedures
•Allows the high-volume testing to be automated while the
labour-intensive cytology is restricted to only the HPV+
samples
• One technician can do 720 HPV samples in one
laboratory shift compared to 40-100 Paps
•Volume of cytology is reduced by 75-90%
•The HPV+ cytologies are the ones with the cytological
abnormalities - cytotechs spend less time looking at
normal slides and more time looking at abnormal slides
• improved job satisfaction & maintenance of skills
42
HPV Vaccination
Two prophylactic HPV vaccines:
• Merck (MSD/Sanofi Pasteur MSD)
• HR-HPV 16 & 18, responsible for ≈70% of cervical
cancers
• LR-HPV 6 & 11, responsible for ≈90% of genital
warts and a number of low-grade abnormal Pap
smears
• GSK
• HR-HPV 16 & 18, responsible for ≈70% of cervical
cancers
• New AS04 adjuvant which is claimed to produce an
enhanced immune response
45
HPV Vaccination
Future II Study Group, NEJM 2007: Merck/MSD, HPV 6 11 16
18, women aged 15-26 with 4 or fewer sexual partners
Per protocol, effic Unrestricted susc Intention to treat, Intention to treat,
acy for vaccine ty eptible populatio vaccine types all types
pes n % (95% CI)
% (95% CI) % (95% CI) % (95% CI)
46
HPV Vaccination
Harper et al. Lancet 2004, 2006: GSK, HPV 16 18, women
aged 15-25 with 6 or fewer sexual partners
Age Ra Efficacy-Persiste Efficacy-Cytolog Efficacy-CIN 1+
nge nt Infection y LSIL+
Per-protocol p 15-25 y 100% 93% 100%
opulation at 53 ears (95% CI: 34-100) (95% CI:71-92) (95% CI: 42-100)
months for typ
es 16 & 18
47
HPV Vaccination
The two prophylactic HPV vaccines:
• Have largely equivalent efficacy for the HPV types
contained in the vaccines
• Have high efficacy if given before exposure to HPV
– i.e. if given to girls or women before the start of
sexual activities
• Have reduced efficacy if given to women who are
sexually active
• Have a clear role in cervical cancer prevention
strategies through the mass vaccination of pre-
sexually active adolescent girls
• Will not replace cervical screening programmes
48
Terima Kasih